Can hosts tolerate avian brood parasites? An appraisal of mechanisms

Can hosts tolerate avian brood parasites? An appraisal of mechanisms Abstract Theoretical work has long stressed the need of studying in concert defenses based on resistance (i.e., mechanisms minimizing the frequency of effective parasite attacks) and tolerance (i.e., mechanisms minimizing the impact of parasites after a successful attack) to achieve a full understanding of host–parasite evolutionary dynamics. The study of tolerance can be particularly illuminating in the comprehension of avian brood parasite–host interactions because if hosts can tolerate parasitism this may resolve the long-lasting paradox of why some hosts do not reject parasite eggs despite costly parasitism. Surprisingly, although the study of host defenses against brood parasites is a hot spot for research in behavioral ecology, empirical studies of tolerance are very rare. Here, I first identify the main reasons explaining reluctance to incorporate tolerance in the study of avian brood parasite–host interactions. Tolerance defenses have been neglected because: 1) behavioral ecologists have primarily targeted on antagonistic coevolution which is most likely selected by resistance; 2) because tolerance (contrary to resistance) cannot be easily measured on host individuals; and 3) because there is a limited knowledge about the mechanisms of tolerance. In a second step, I review current evidence about tolerance in hosts and propose yet unexplored mechanisms to be studied based on parental investment theory. Finally, I propose an experimental framework based on well-established knowledge about phenotypic plasticity that can help detecting the effects of tolerance in future studies. I urge behavioral ecologists to embark on suggested mechanistic approaches to study tolerance defenses to achieve a better comprehension of avian brood parasite–host coevolution. INTRODUCTION Once faced with parasites hosts can protect themselves from their harmful effects through defenses based on resistance and/or tolerance (Svensson and Råberg 2010). Resistance involves defensive mechanisms minimizing the frequency of effective parasite attacks either by avoiding the parasite or directly attacking it (Read et al. 2008; Råberg et al. 2009), and it is operationally measured as the inverse of parasitism load (i.e., the lower the number of parasites per host, the more resistant is the host) (Råberg et al. 2009). Tolerance includes defensive mechanisms minimizing the negative impact of the parasite after a successful attack (Read et al. 2008; Råberg et al. 2009), and it is operationally measured as the slope of a regression between host fitness against parasitism load (i.e., the stepper the slope, less tolerant is the host) (Råberg et al. 2009). In other words, tolerance can be defined as the rate of change in host fitness as parasite burden increases (Råberg et al. 2009). Both resistance and tolerance are costly traits for hosts, but contrary to resistance, tolerance diminishes the impact of parasite without causing direct negative effects in the parasite (Roy and Kirchner 2000; Svensson and Råberg 2010). Due to its negative effect on parasite fitness, resistance can select for counter-defenses in parasites, which, in turn, may also select for improved host resistance, thereby resulting in a coevolutionary arms race of defenses and counter-defenses (Chisholm et al. 2006). Tolerance, however, will not select for parasite counter-defenses and rarely result in a coevolutionary arms race (Råberg et al. 2009; Svensson and Råberg 2010). Based on this difference, theoreticians have long stressed the need of considering separate costs and effects of tolerance and resistance to attain a wider comprehension of epidemiological dynamics and host–parasite coevolution (Roy and Kirchner 2000; Restif and Koella 2004; Read et al. 2008; Råberg et al. 2009; Svensson and Råberg 2010). However, studies of animal victim–enemy interactions focusing on tolerance defenses are scarce and confined to report variation in operational tolerance in infection experiments with tadpoles (Rohr et al. 2010; Sears et al. 2015), and monarch butterflies (Sternberg et al. 2013). Therefore, we know very little about the possible mechanisms of tolerance in wild animals, and understanding how victims might tolerate their enemies remains a major gap in animal ecology. The interaction between avian brood parasites and their hosts provides fascinating examples of the evolution of defenses based on resistance (Davies 2000). Interspecific brood parasitism is a reproductive strategy in which the parasitic species lays its eggs in the nest of another species, the host, which carries out the parental duties, from the incubation of eggs to chick feeding (Davies 2000; Feeney et al. 2014). Brood parasitism often imposes large costs to hosts due to egg breakage during egg laying by parasite females, rejection of host eggs and/or chicks from the nest by the parasite chick, and starvation of host chicks due to parasite chick monopolization of parental feeds (Rothstein 1990). Consequently, natural selection has favored the evolution of certain behaviors preventing cuckoo parasitism (i.e., resistance mechanisms) such as mobbing of parasites before laying (e.g., Røskaft et al. 2002; Welbergen and Davies 2009), parasite egg discrimination and rejection (e.g., Davies and Brooke 1988; Soler and Møller 1990; Avilés et al. 2010; Spottiswoode and Stevens 2010), or nestling discrimination (e.g., Langmore et al. 2003; Grim 2007; Sato et al. 2010). Resistance defenses have selected for further counter-defenses in the brood parasites, such as hawk-like cuckoo plumage to avoid host aggression (Davies and Welbergen 2008), more accurate host egg mimicry (Avilés 2008; Stoddard and Stevens 2010) or nestling phenotype matching (Langmore et al. 2011) to avoid egg or fledging rejection, resulting, in many instances, in a coevolutionary arms race (Davies 2000). Although a clear model system for the study of host defenses based on resistance, avian brood parasites may have selected for host tolerance as well (Svensson and Råberg 2010). This is so because defenses based on resistance can be costly due to recognition and rejection errors (Lotem et al. 1995), or because parasites may destroy host eggs after being aware of host resistance (i.e., mafia behavior)(Soler et al. 1995; Hoover and Robinson 2007), a scenario likely to promote the evolution of defenses based on tolerance (Svensson and Råberg 2010). In their seminal review Svensson and Råberg (2010) argued that hosts of avian brood parasites may defend against cuckoo parasites by modifying their breeding strategy to minimize the costs of brood parasitism. In theory, there are 2 ways that tolerance adaptations could work. One is a fixed response involving a genetic change in a host trait that minimizes the cost of brood parasitism, and another is plasticity in the suggested trait that turns on a tolerance mechanism only when it is needed. In the first scenario the cost of parasitism would select for changes in the life-history strategy of the host to optimize allocation over the entire life-time of the host. Fixed responses can be detectable with comparative analysis that involves comparisons among species or populations exposed to different level of parasitism. Indeed, prevailing empirical support for tolerance would come from a handful of studies comparing host life-history traits in parasitized and nonparasitized populations and showing increased clutch size (Soler et al. 2001; Cunningham and Lewis 2006) or smaller clutches combined with several nesting attempts (Petit 1991; Brooker and Brooker 1996; Anderson et al. 2013; Louder et al. 2015) in parasitized host populations. Plastic responses, however, would allow reducing the impact of a specific brood parasite in the current reproduction, but their role have been neglected despite compiling evidence that variation in phenotipic plasticity within species may strongly contribute to parasite dynamics (e.g., Gervasi et al. 2015). Previous theoretical work has suggested that tolerance and resistance in host of avian brood parasites are not mutually exclusive evolutionary responses to costly brood parasitism (Medina and Langmore 2016), and empirical evidence on magpie host parasitized by great spotted cuckoos suggest that tolerance and resistance can be present within the same population (Soler et al. 2011). Host life-history adjustments may reduce the survival of the parasite as well as mitigate the cost of parasitism when the parasite does survive, which makes difficult to ascribe them to tolerance or resistance. The fact that resistance and tolerance responses might not be mutually exclusive components of host defense against brood parasites has not been previously considered, but may have depth implications for the study of host tolerance, which I describe more fully below. Svensson and Råberg (2010) stressed that tolerance is likely to play a fundamental role in the evolutionary dynamic of brood–parasitic interactions because whether a host can tolerate cuckoos, this may help explaining the classic paradox of why some hosts exhibit a noticeable absence of resistance defenses despite costly parasitism (see also Kilner and Langmore 2011). The theoretical consequences of considering tolerance defenses have been recently expanded in 2 review articles. Medina and Langmore (2016) have stressed that whether a host resist or tolerate a brood parasite will determine the chance of detecting antagonistic coevolution (i.e., coevolution will be a less likely outcome when the hosts tolerate). Moreover, Soler and Soler (2017) have argued that the diversification rate of avian brood parasites should be lower whether host defenses are based on tolerance. Surprisingly, despite recent advances in theoretical grounds about consequences of considering tolerance in the study of cuckoo–host interactions, we still have very few examples of tolerance defenses, and a very poor understanding of the possible mechanisms behind tolerance defenses (Medina and Langmore 2016). Identifying the mechanistic basis of tolerance remains a logical next step as it will help balancing currently disproportioned theoretical and empirical evidence to provide a more integrative framework for the study of cuckoo–host evolutionary dynamics. Hence, here I will focus on a fundamental issue that was not treated in depth in previous reviews, namely the study of the mechanistic basis of tolerance defenses in hosts of avian brood parasites. In a first step I will identify the main reasons explaining reluctance to incorporate tolerance in empirical studies of cuckoo–host interactions. In a second step I will thoroughly review current evidence of tolerance mechanisms in hosts of avian brood parasites and propose yet unexplored alternative mechanisms to be investigated based on parental investment theory. Finally, I will propose a novel experimental framework based on well-established knowledge about phenotypic plasticity that can help detecting the subtle effects of tolerance in future studies of avian brood parasitism. WHY DOES RELUCTANCE TO STUDY TOLERANCE PERSIST? Despite recent theoretical advances in the understanding of the evolutionary consequences of considering tolerance defenses (Svensson and Råberg 2010; Feeney et al. 2014; Medina and Langmore 2016; Soler and Soler 2017), yet the concept and the study of tolerance have only been minimally integrated in the study of the evolutionary interactions between avian brood parasites and their hosts. In the only explicit test of the adaptive value of tolerance in a brood parasitic system, Soler et al. (2011) found that operational tolerance (i.e., the slope of the regression between the number of cuckoo eggs in a clutch and the number of fledglings produced) in the European Magpie (Pica pica), host of the great spotted cuckoo (Clamator glandarius), differed among host populations. In addition, tolerance was found to be larger in magpie populations suffering high levels of parasitism, suggesting that it may have evolved as an adaptive response to cuckoo parasitism in magpies (Soler et al. 2011). Also, and based on a modeling approach, Takasu and Moskat (2011) concluded that host tolerance together with host immigration may explain the long-term persistence of heavy cuckoo parasitism on Hungarian great reed warblers (Acrocephalus arundinaceus). Although these studies provide some evidence of the adaptive value of tolerance in compensating brood parasitism costs, the mechanistic basis of tolerance defenses against avian brood parasites remains elusive. Indeed examination of published items in the WEB OF SCIENCE reveals a lack of studies considering the role of host defenses based on tolerance. Only 6 out of 250 papers published after publication of the Svensson and Råberg (2010) review including the search term “avian brood parasitism” either in the title, abstract or keywords also included the term “tolerance defense”, representing a meagre 0.02% of all studies (search performed on 9 February 2017). Below I identify 3 mutually nonexclusive reasons that may help explaining this bias against the study of tolerance defenses. Historical reasons Tolerance against parasites do not generally result in coevolution (Svensson and Råberg 2010), whereas avian brood parasitism has largely been recognized as an ideal model system for studying antagonistic coevolution (Rothstein 1990; Davies 2000; Kilner and Langmore 2011; Soler 2014). As a consequence, evolutionary biologists have largely targeted the study of resistance which is likely to select for new forms of counter-resistance in brood parasites, which may subsequently select for more elaborated forms of host resistance. Hence, an impressive body of empirical evidence about host resistance mechanisms and parasite trickeries has been accumulated in different avian brood–parasite–host systems, whereas evidence for tolerance is only very recent and anecdotal. Mistreatment of tolerance may also be due to the fact that most early seminar empirical work was based on the interaction between the evicting common cuckoo and their hosts (e.g., Davies and Brooke 1988; Lotem et al. 1995). It is hard to imagine how tolerance may evolve if the cuckoo chick evicted all the host eggs or nestlings from the nest. Achieving a better knowledge of the full array of tolerance mechanisms exhibited by different hosts, and, of the evolutionary consequences of having evolved tolerance for the dynamics of their interactions with their avian brood parasites will probably help to change the misconception that avian brood parasite–host systems mostly serve to study coevolution. Operational tolerance is a feature of populations not of individuals Quantifying tolerance is a major issue in studies of animal victim–enemy interactions in general (Råberg et al. 2009), and of avian brood parasite–host interactions in particular (Medina and Langmore 2016). Two main approaches have been proposed, both requiring studying the fitness outcome of avian brood parasite–host interactions in several populations (reviewed in Medina and Langmore 2016). On one hand, tolerance can be operationally estimated as the reaction norm of host fitness against level of parasitism, the steeper the slope of the regression is, the lower the tolerance (“range tolerance” sensu Medina and Langmore 2016; Svensson and Råberg 2010). Alternatively, host fitness could be compared in 2 populations exposed to the same level of parasitism, the one with the highest fitness being the more tolerant (“point tolerance” sensu Medina and Langmore 2016). These approaches, however, may lead to flawed conclusions about the role of tolerance if the populations a priori differed in the qualities of the hosts, because, in such a case, differences in fitness between the populations would have nothing to do with defenses against brood parasites (see discussion in Svensson and Råberg 2010). Calculation of operational tolerance is a prerequisite for studying the adaptive value of host defenses against brood parasites (e.g., Soler et al. 2011), but mechanisms cannot be elucidated based on operational tolerance and tolerance mechanisms need to feasibly underlie patterns of operational tolerance. In addition range and point tolerance do not allow identifying whether individual hosts within parasitized population may differ in tolerance as they do in resistance. Previous theoretical work has suggested that the evolution of tolerance defenses may limit the evolution of resistance (Svensson and Raberg 2010), which can be tested by assessing if tolerance and resistance are correlated across host individuals within a given population. I argue that reluctance to study tolerance is partly due to the fact that evolutionary biologists working on brood parasitism have not been able to feasibly envisage how to test for tolerance at the individual level, and that a more mechanistic conception of the study of tolerance defenses may contribute to alleviate this issue (see below). Mechanisms of tolerance are unknown and evidence for true tolerance is not conclusive We have a very poor understanding of tolerance mechanisms in hosts of avian brood parasites, possibly due to the fact that defenses based on tolerance are much more subtle and, thus, less detectable than those based on resistance. In Table 1, I have summarized published studies where a mechanism of tolerance to brood parasites was reported by Medina and Langmore (2016), as well as other previously noncited studies that may also suggest host tolerance. Aiming to discern whether costs of brood parasitism may relate to a particular tolerance mechanism, I have classified these studies based on whether parasites share the nests with host offspring or not. I also have reported whether evidence of a resistance mechanism exists for that host, so that I can tentatively assess if there exists a relationship between resistance and tolerance mechanisms. Table 1 Evidence of mechanisms of tolerance against avian brood parasites Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  *Rejection behavior has not been studied. View Large Table 1 Evidence of mechanisms of tolerance against avian brood parasites Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  *Rejection behavior has not been studied. View Large Examination of these 10 studies reveals that most evidence of tolerance came from a handful of studies reporting a modification of the host breeding strategy in parasitized nests (9 of 10 studies cited in Table 1). Specifically, changes in host breeding strategy may entail increasing (reported in 2 studies in 2 different brood parasite-host systems) or decreasing clutch size (reported in 2 studies, one with a host of one Australian cuckoo and another comparative study based on 29 brown-headed cowbird Molothrus ater hosts), increased proneness to multiple brooding (i.e., reported in 6 studies in several hosts of the brown-headed cowbird, but also in one host of one Australian cuckoo), increased maternal investment in host eggs (reported in one study with 2 brown-headed cowbird hosts) or acceleration of host nestling development (reported in one comparative study with 134 brown-headed cowbird hosts) (Table 1). Thus, except for 2 studies that reported an increase of clutch size (Table 1), all other sources of evidence would concur with a general host strategy of reducing parasitism costs by shortening and fractioning host reproductive events within a single season. It has been previously suggested that whether hosts will opt to increase or reduce their breeding investment in currently parasitized broods might ultimately depend on the extent of parasitism costs (Medina and Langmore 2016). For instance, where brood parasites are raised together with host nestlings, hosts may diminish the relatively small damage caused by laying brood parasites through increasing their clutch size. Laying extra eggs may thus function as an insurance strategy against this small damage. This appears to be the case of the Montezuma Oropendolas Psarocolius montezuma parasitized by the Giant cowbird Scaphidura oryzivora (Cunningham and Lewis 2006) (Table 1). The insurance hypothesis, however, would not apply to Eurasian magpie parasitized by the Great spotted cuckoo (Soler et al. 2001), because once the great spotted cuckoo nestling hatches it will invariably starve all the host offspring, and thus the fitness benefits of laying an extra eggs will disappear. In contrast, where costs of parasitism are large because host nestlings or eggs are evicted by the parasite, it would be advantageous for the hosts to reduce their clutches and to increase the number of broods to raise per breeding season, as it was reported for Splendid fairy-wren Malurus splendens parasitized by Horsfield’s Bronze-cuckoos Chalcites basalis in Autralia (Brooker and Brooker 1996) and for Gray warblers Gerygone igata parasitized by Shinning Bronze-cuckoos Chalcites lucidus in New Zealand (Anderson et al. 2013). However, multiple brooding linked to parasitism has also been reported in several hosts of brown headed cowbirds where parasites are raised together with host nestlings (Smith 1981; Petit 1991; Louder et al. 2015). Also, comparative evidence has shown that host species largely exposed to cowbird parasitism in North America have lower clutch sizes and larger number of breeding attempts than new hosts (Hauber 2003a). In a second comparative study, Remeš (2006) found that brown-headed cowbird host species suffering high rate of parasitism showed shorter nesting periods, which suggests that faster growing and shorter incubation may have been selected in evolutionary time as tolerance mechanisms to lessen the costs of cowbird parasitism. A global interpretation of these findings in terms of costs of parasitism, however, might be problematic as currently assumed low costs of parasitism in some systems may indeed reflect the effect of tolerance selected in the pass. Evidence of tolerance has accumulated in host species that do not reject parasitic eggs at all, as in some hosts of Australian Chalcites species or in brown-headed cowbird hosts, as well as in hosts that can reject model eggs (Table 1). Therefore, it seems that, in general, the evolution of resistance would have not limited the evolution of tolerance mechanisms in hosts of avian brood parasites. It must be highlighted, however, that although these studies provide tentative evidence of host tolerance in several different systems, none was specifically designed to study tolerance defenses. Indeed, a comprehensive analysis of the study designs in these studies reveals that in all cases one or several alternative explanations to the hypothesis of tolerance can account for the patterns found (see Table 1). In particular, selection by avian brood parasites of host individuals, populations and species with particular breeding attributes is a likely alternative explanation that held possible for all these studies (Table 1). Moreover, previous theoretical and empirical work has interpreted changes in host life-history traits in response to brood parasitism as evidence of tolerance (Svensson and Raberg 2010; Soler et al. 2011; Medina and Langmore 2016), which may have help expanding the false impression that there are distinct resistance responses and distinct tolerance responses toward brood parasites. This may be the case for some host responses like egg rejection, which can unambiguously be ascribed to resistance. However, most of host life-history adjustments in response to parasitism (e.g., hatch patterns or clutch size adjustments), which currently constitutes the basis of the empirical support for tolerance (see above), could in theory involve aspects of both—reduce the survival of the parasite (i.e., resistance) as well as mitigate the costs of parasitism when the parasite does survive (i.e., tolerance) (see above). Summing up, current evidence of tolerance is still inconclusive and very scarce and further experimental studies controlling for possible confounding variable are needed to critically assess to what extent hosts of avian brood parasites may compensate for the costs of raising parasitic chicks. An appraisal of mechanisms favoring cuckoo tolerance It is known that female birds may modify their reproductive investment affecting offspring phenotype in ways that increase female fecundity in response to changes in the environmental conditions (maternal effects sensu Mousseau and Fox 1998). Once successfully parasitized, hosts may potentially buffer the harmful effect of parasitism through modification of an array of behavioral, life-history and physiological traits, most of them never studied in the frame of tolerance defenses. I identify several different host traits that can potentially be modified after parasitism through pre- and postnatal maternal effects (Figure 1) and that may provide fitness benefits for the hosts worth exploring in future experiments. Figure 1 View largeDownload slide Measurable hosts traits that may potentially suggest evidence of a tolerance mechanism in relation to host reproductive cycle. Hosts can plastically modify behavioral, life-history and physiological traits after a parasitism event. Figure 1 View largeDownload slide Measurable hosts traits that may potentially suggest evidence of a tolerance mechanism in relation to host reproductive cycle. Hosts can plastically modify behavioral, life-history and physiological traits after a parasitism event. Experimental work has shown that birds have the potential to plastically adjust their reproductive behaviors (i.e., including incubation and feeding behaviors) in response to changes in risk of nest predation (Fontaine and Martin 2006; Martin and Briskie 2009). Also, in the context of brood parasitism, experiments have shown that in American coots Fulica americana parents are able to modify the intensity and direction of incubation (Lyon 2007; Shizuka and Lyon 2011). Therefore, a promising field to understand tolerance deeply in systems where host offspring is raised together with a parasite, is studying if parasitized individuals may modify their reproductive behaviors once parasitized to minimize the costs of parasitism. It is well known that through the modification of their incubation pattern, birds are able to modify the degree of hatching asynchrony of their clutches (reviewed in Magrath 1990). Moreover, comparative and experimental evidence suggest that hatching synchronously reduces the costs of parasitism in hosts of brown-headed cowbirds (Hauber 2003b). Thus, it can be hypothesized that hosts may minimize the losses of nestlings to parasitic chicks by producing synchronous broods. Another possibility explored theoretically is that host parents increased their feeding effort in parasitized nests to minimize the chance of starvation of their own offspring in their competition with the parasitic chick (Holen and Johnstone 2007). However, it could also be predicted that parents opted to reduce their feeding effort in parasitized nests saving energy for future breeding attempts (see Figure 2). Although expectations about how hosts may modify their behaviors to minimize the cost of raising a parasitic chick may ultimately depend on the tolerance strategy of the species (see Figure 2), the study of plasticity in reproductive behaviors in response to brood parasitism may open new avenues in our understanding of host tolerance against brood parasites. Figure 2 View largeDownload slide Host tolerance strategy in relation to brood parasitism virulence. Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impact on host fitness through outcompeting or complete eviction of their offspring. Alternatively, host may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with the host offspring. Tentative expectations of how host may modify behavioral, life-history and physiological traits in response to brood parasitism depending of one tolerance strategy or another are presented. Figure 2 View largeDownload slide Host tolerance strategy in relation to brood parasitism virulence. Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impact on host fitness through outcompeting or complete eviction of their offspring. Alternatively, host may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with the host offspring. Tentative expectations of how host may modify behavioral, life-history and physiological traits in response to brood parasitism depending of one tolerance strategy or another are presented. Several sources of evidence have shown that birds have the potential to plastically adjust their life-history traits (i.e., egg size and clutch size) in response to increased perceived predation risk (Lima 2009; Martin and Briskie 2009; LaManna and Martin 2016). In addition, experimental studies have shown that in birds, females have the potential to modify their investment on eggs (i.e., hormone composition and egg size) in response to a sudden change in environmental conditions during laying (Saino, Romano, Caprioli, et al. 2010; Saino, Romano, Rubolini, et al. 2010; Parejo et al. 2012). Therefore, in host species in which the offspring is raised together with a parasitic chick it might be advantageous to parasitized hosts increasing the size of their eggs, as it positively relates with the size and competitiveness of nestlings (Krist 2011). However, where parasitic chicks are raised alone, or where an increase in egg size does not reverse the highest competitiveness of the parasitic nestlings over the host ones, host could opt to save as much energy as possible for future reproductive events by reducing eggs and clutches. It is, thus, critical considering that in species where multiple brooding is possible, the study of tolerance should embrace all possible breeding attempts as the benefits of reducing the investment after being parasitized (i.e., a prerequisite for tolerance being detected) might only be detected by considering together host investment in current versus future breeding attempts. Finally, another poorly explored possibility is that tolerance primarily comes by physiological maternal effects. Hahn et al. (2017) have recently found that eggs of the American redstart Setophaga ruticilla and the Red-eye vireo Vireo olivaceus exhibited higher levels of yolk testosterone in nests that were parasitized by the brown-headed cowbird than in nonparasitized nests. Given compelling evidence showing that elevated levels of yolk testosterone in the eggs accelerate embryo development and nestling growth, shorten the incubation period and increase the intensity of begging behaviors in birds (Schwabl 1993, 1996), these findings are consistent with the possibility that hosts, through maternal effects, may modify their offspring phenotype to diminish the costs of sharing the nest with a parasite chick. The interpretation of Hahn et al. (2017)’s results is difficult, however, because hormone levels in the eggs were estimated on entire clutches and therefore it cannot be discarded that cowbirds were selecting nests by host qualities related to hormone levels. Another simple alternative hypothesis would be that parasitism is associated with aggressive encounters with the brood parasite, and that the elevated testosterone level in eggs is a simple side-effect of such an increase in aggression and testosterone in females. Moreover, some studies have found a relationship between maternal yolk hormones in the eggs and sex determination (Petrie et al. 2001; but see Eising et al. 2003), raising the yet neglected possibility that hosts may bias the sex of their offspring toward the more competitive sex, or the most dispersive one when being parasitized. Therefore, the study of maternal yolk hormones in the eggs in response to parasitism and of the possible effects of these hormones on the array of behavioral (i.e., begging intensity), life-history (i.e., growth rates) and physiological (i.e., nestling immunity) host traits likely related to fitness appear obvious next steps in our understating of tolerance mechanisms. It must be highlighted, however, that many of the putative mechanisms for host tolerance I have here described might potentially impose harm on the brood parasite and thus may lead to an evolutionary arms race of attack and host resistance. For example, hosts may attempt to synchronize hatching of the clutch and the parasite’s best response would then be to shorten its incubation period to get a head start and regain its competitive advantage. Testing if parasite fitness is decreased in response to the change in a host trait is a fundamental step to discard that “tolerance” leads to an escalation of the costs of parasitism and a likely switch to resistance in the host. Strategies of tolerance I envisage 3 possible host tolerance strategies depending on how much brood parasitism impacts on host fitness (see Figure 2). Each one has particular expectations regarding how behavioral, life-history and physiological traits of hosts should differ between parasitized and unparasitized nests in a population, which I have summarized in Figure 2. Whenever parasitism imposes high costs to hosts, that is, when differences in size between host and parasite nestlings raised together are large in favor of the parasitic nestling and, in systems where parasites are raised alone by the hosts, it may pay hosts following a strategy of “saving energy” for future breeding attempts through a reduction of current reproductive investment. The frequently reported observation that parasitized nests or populations of some brown-headed cowbird hosts, but also some Australian cuckoo hosts (Table 1), have lower clutch sizes that nonparasitized nests may suggest that the “saving energy” strategy could be a widely spread evolutionary solution to counteract costly brood parasitism. Besides reducing clutch size, hosts may save energy reducing egg size or the amount of costly maternal hormones deposited in their eggs, which may bias their offspring sex-ratio towards producing the less energetically demanding sex (Figure 2). The “save energy” strategy may also imply a lower attendance of nests during incubation and nestling provisioning in parasitized nests, which may potentially result in larger hatching asynchrony or decelerated growing (Figure 2). These possibilities have not yet been investigated. A second possible tolerance strategy when facing highly virulent brood parasites that impose intermediate cost is to shorten as much as possible the development of the offspring to increase the chance of having another breeding attempt in the season. Shortening might be achieved through prenatal maternal effects. For instance, female hosts may modify the amount of androgens in the eggs in parasitized nests (Hahn et al. 2017). High level of steroid hormones in the egg yolk accelerates embryo development and growth rates, and favors a more vigorous begging of nestlings, which may also induce higher levels of parental provisioning by hosts (Figure 2). Also, through modification of hormone levels in the eggs hosts may potentially bias their offspring sex-ratio towards the sex with a faster development (Figure 2). Behavior may also play a role in the “shortening” strategy. For instance, hosts may intensify their incubation promoting lower hatching asynchrony and thus the shortening of the nestling dependence period if food conditions are good enough and parents can provide enough feedings (Figure 2). Finally, shortening might also arise from postnatal parental effects if parents increased their provisioning rate when parasitized irrespective of intensity of begging display (Figure 2). It must be considered that whether a host opt by a “save energy” or a “shortening” strategy is likely depending on environmental conditions. The “shortening” strategy implies higher breeding investment in the short time than the “save energy” strategy, and therefore will be a most likely tolerance strategy where hosts faced good environmental conditions. Also the pace of life of hosts is likely to determine the chance of these 2 strategies, with “slow-paced” hosts with slow development rates and long life spans being less able to opt by a “shortening” strategy than “fast-paced” hosts (e.g., Sears et al. 2015) Alternatively, where differences in size between parasite and host nestlings are small, and therefore where parasitism is not that costly, it may pay hosts increasing their breeding investment to enhance the competitiveness of their offspring in the battle with parasitic nest-mates. So far evidence for this “preparing for battle” strategy is scant, and indirectly came from a single study showing increased level of maternal androgens in the eggs of American redstart and red-eyed vireo nests parasitized by brown-headed cowbirds (Hahn et al. 2017). In these 2 species, a proportion of host nests fledge one or more host nestlings together with the cowbird fledging. Therefore, it could be argued that in parasitized nests parents may modify the amount of maternal androgens in the eggs aiming to accelerate growing and begging of their offspring, as this may increase their survival. In the same vein, in sexually dimorphic hosts, it would be expected that parent may bias the sex of their offspring toward the bigger sex, as this would have greater chance of not being outcompeted by the parasite nest-mate. It must me considered, however, that the “preparing for battle” strategy could also be a resistance strategy if the increase in competitiveness of host chicks impacts the parasite chicks. Therefore, it is critical to assess whether the host responses may harm the parasites to ensure that we are dealing with a true tolerance strategy (see below). The “preparing for battle” and the “shortening” strategies have identical expectations for growth rates and begging displays in parasitized nests (see Figure 2). This is so because a faster development of the offspring will give host parents more chance of having a second reproduction in the same season, but also will increase the survival of their offspring through early hatching and a more effective competition for parental food delivery with the parasite nestlings. Twofold benefit of a faster development is perhaps behind the general pattern of faster growth rate reported among hosts suffering higher level of parasitism in cowbird hosts Remeš (2006). However, the 2 strategies can be differentiated in the wild because they have different expectations regarding egg size and clutch size that are likely to increase in parasitized nests under a “preparing for battle” strategy. As reported above, laying extra eggs may function as an insurance strategy against small damage (Cunningham and Lewis 2006). Also larger eggs will produce bigger nestlings that will compete better with parasite nest-mates. Sex-ratio expectations also differ for the 2 strategies, being the more competitive sex (i.e., the bigger) over the one with a faster development, the more likely selected under a scenario of nestling competence. A reaction norm approach for the study of tolerance Tolerance could be achieved through plasticity in resource allocation in response to brood parasitism. Phenotypic plasticity is the property of a genotype to produce different phenotypes in response to different environmental conditions (Pigliucci 2005). Plasticity in resource allocation in response to environmental stress is among the most commonly studied tolerance mechanism in plants (reviewed in Strauss and Agrawal 1999), although their role is still poorly understood in animal-enemy interactions. Several sources of empirical evidence have shown that variable risk of predation may induce plasticity in life history, behavioral and physiological traits in birds (Martin and Briskie 2009; Lima 2009a; LaManna & Martin 2016). Also, previous experimental studies have suggested that hosts of avian brood parasites may respond plastically to risk of parasitism through changes in defenses based on resistance (Davies and Brooke 1988; Moksnes et al. 1993; Welbergen and Davies 2012). Moreover, a recent study has relied on the reaction norm approach to estimate individual tolerance in the Soay sheep (Ovis aries) in response to a gastrointestinal nematode parasite (Hayward et al. 2014). However, although it should be at the core of the study of tolerance mechanisms, it remains unstudied whether variable levels of brood parasitism may induce plastic changes in life-history, behavioral or physiological traits of their hosts that may help them to minimize the harmful effects of parasitism. I argue that adopting a phenotypic plasticity framework to simultaneously study host traits and fitness as individual-specific reaction norms related to intensity of parasitism is critical to achieve a full understanding of tolerance mechanisms and the adaptive value of tolerance. In this context, the reaction norm would be the repertoire of phenotypic and fitness responses of a host genotype along a gradient of brood parasitism, and hence a property of individuals. I have summarized in Figure 3 how to study host tolerance to brood parasitism based on reaction norm approach (Figure 3). Figure 3 View largeDownload slide A reaction norm approach for the study of tolerance mechanisms in hosts of avian brood parasites. The figure shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the individual reaction norm in 1) resource allocation and 2) fitness of these 2 individuals. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In panel a, slope of the individual 1 is stepper than slope of the individual 2, implying that individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than individual 2. In panel b, however, slope of the relationship between parasitism level and fitness is stepper for individual 2 than for individual 1, meaning that the former is the less tolerant. Figure 3 View largeDownload slide A reaction norm approach for the study of tolerance mechanisms in hosts of avian brood parasites. The figure shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the individual reaction norm in 1) resource allocation and 2) fitness of these 2 individuals. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In panel a, slope of the individual 1 is stepper than slope of the individual 2, implying that individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than individual 2. In panel b, however, slope of the relationship between parasitism level and fitness is stepper for individual 2 than for individual 1, meaning that the former is the less tolerant. Figure 3 shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the reaction norm in 1) resource allocation and 2) fitness of each individual host. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In the panel a, the slope of the individual 1 is stepper than the slope of the individual 2, meaning that the individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than the individual 2. In the panel b, however, the slope of the relationship between parasitism level and fitness is steeper for the individual 2 than for the individual 1, meaning that the former is the less tolerant. The reaction norm approach described in the Figure 3 contributes to the study of tolerance mechanisms in at least 3 fundamental ways: 1) First, it allows studying tolerance defenses at the individual level, and, therefore, to differentiate between more or less tolerant hosts within a population, such as it has been largely done for defenses based on resistance (Figure 3). Hence, this approach place tolerance and resistance at the same level and provides an unique opportunity for testing whether host plasticity in resource allocation (i.e., tolerance) may have limited the evolution of resistance defenses as some theoretical models have proposed (e.g., Svensson and Råberg 2010). 2) Second, the combined visualization and analysis of host individual reaction norms in phenotype and in fitness in relation to parasitism level provides a unique opportunity for identifying the mechanistic basis behind tolerance defenses. Moreover, this will allow testing the very relevant question of whether the most plastic host individuals are the most tolerant as well. 3) Third, this approach allow quantifying genetic variation in tolerance in the population based on variation in slopes and height of all fitness reaction norms of the individuals in the population (e.g., Ghalambor et al. 2010), which is necessary in any attempt of quantifying the genetic basis of differences in tolerance defenses among populations and species. HOW TO STUDY MECHANISMS OF TOLERANCE IN THE WILD? Two main kinds of studies at the population level may help to shed light on the mechanistic basis of tolerance: Longitudinal studies on marked host individuals Several seminal studies in the field of phenotypic plasticity have acknowledged that the reaction norm is ultimately a property of genotypes (e.g., Stearns 1989; Agrawal 2001; Ghalambor et al. 2010). Therefore, to study host tolerance defenses based on the reaction norm paradigm one would need to sample behavioral, life-history and physiological traits and fitness of individual hosts along a gradient of parasitism. In practice, this would mean marking host individuals in a population and monitoring every breeding attempt in their life. Moreover, for every breeding attempt, it should be necessary to record the intensity of parasitism (i.e., number of parasite eggs found in the nest), the final reproductive outcome (i.e., a fitness correlate), and to quantify all possible life-history, behavioral and physiological traits likely to play a role as tolerance mechanisms listed in Figure 1. Finally, an additional thing to measure would be if and how much variation in host traits thought to be mechanism of tolerance also impact the success of the brood parasite. If the responses harm the parasite then the trait may actually be a subtle form of resistance rather than tolerance. The longitudinal approach has been used by Hayward et al. (2014), who applied random regression models to longitudinal data of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. This study revealed that individuals greatly differ in tolerance, and that the more tolerant ones produced more offspring over the course of their lives (Hayward et al. 2014). A recent longitudinal study in magpie hosts parasitized by the great spotted cuckoo in Spain has shown the importance of sampling several times across the lifetime of individuals to attain a reliable assessment of defenses based on resistance (Molina-Morales et al. 2014). Extending studies like this to include life-history, behavior and physiological features of hosts appears a logical next step to achieve a full understanding of defenses based on tolerance. Experimental studies Plasticity in resistance defenses has been widely studied through manipulation of perceived risk of parasitism at the host nest during laying and incubation (Davies and Brooke 1988; Moksnes et al. 1993; Welbergen and Davies 2012). A similar experimental approach combined with the quantification of life-history, behavior and physiological responses of the hosts may greatly enhance our understanding of the role of plastic responses and tolerance defenses against brood parasites. This approach would require having previous understanding of the natural history of the system and the physiological mechanisms that underlie the behavioral responses, as without this it would be possible to do experiments that yield negative results, which can lead to the incorrect conclusion that nothing interesting is going on. Another possibility is manipulating the level of parasitism itself in host nests and assessing the direct effect of parasite removal on host physiology, behavior, and fitness. Experimental removal of parasites has now successfully been used to study tolerance to ectoparasites in a study on mockingbirds Mimus parvulus and medium ground finches Geospiza fortis parasitized by the nest fly Philornis downsi in the Galapago islands (Knutie et al. 2016). Interestingly, parasitized mockingbird nestlings begged more than nonparasitized mockingbird nestlings, which induced higher parental provisioning that compensated for parasite damage. In this example, however, begging is a trait that happens to provide tolerance to mockingbirds but that was not evolved to deal with the cost of the nest fly which was a novel disease (Knutie et al. 2016). Tolerance traits should be those evolved specifically to deal with the costs of the parasite (Read et al. 2008; Råberg et al. 2009), hence mockingbirds can be considered as a tolerant species although this would not constitute an example of the evolution of tolerance. As noted above, it can be difficult to assign host responses to brood parasitism to resistance or tolerance. Therefore, in combination with manipulations of parasitism (i.e., either risk or true) and the assessment of host responses, it is critical to assess whether host responses (i.e., changes in life-history, behavioral and physiological traits) impacts the parasite. If the trait affects the parasite then it is at least in part resistance, and it might be hard to make the case for tolerance. However, if the trait improves host fitness without impacting the parasite, then it is clearly tolerance. Experiments could get at this for some putative tolerance traits: for example, alter hatching synchrony or clutch size and look at whether parasite fitness is decreased, host fitness is increased or both. Summing up, a logical experimental pathway for the study of tolerance defenses would be first identifying candidate host traits playing a role in tolerance throughout manipulations of parasitism load, and, secondly, the manipulation of those host traits and the study of fitness consequences for the host and parasite, which would help assessing whether host responses are due to tolerance or resistance. CONCLUSIONS Identifying the mechanistic basis of tolerance defenses remains a major challenge in the study of brood parasite–host interactions as it will help merging currently separated theoretical and empirical evidence to provide a more integrative framework for the study of cuckoo–host evolutionary dynamics. Current evidence of tolerance is inconclusive and scarce and experimental studies controlling for possible confounding variables are needed to critically assess to what extent hosts of avian brood parasites may compensate for the costs of raising parasitic chicks. Once parasitized, hosts may buffer the harmful effect of parasitism through modification of an array of behavioral, life-history and physiological traits, most of them never studied in the framework of tolerance defenses. Hosts may tolerate brood parasites using different strategies of breeding investment: Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impacts on host fitness. Alternatively, hosts may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with host offspring. Adopting a phenotypic plasticity framework to simultaneously study host traits and fitness as individual-specific reaction norms related to intensity of parasitism is critical to achieve a full understanding of tolerance mechanisms, and the adaptive value of tolerance. FUNDING I was supported by the Spanish Ministry of Economy and Competitiveness during the redaction of this manuscript (Projects CGL2014-56769-P). I am grateful to D. Parejo, J.G. Martínez, and M. Exposito-Granados for very helpful discussion during the elaboration of the manuscript. I am also deeply grateful to L Simmons by inviting me to write this review and to B. Lyon, and 2 anonymous reviewers for very constructive comments and suggestions. REFERENCES Agrawal AA. 2001. Ecology - Phenotypic plasticity in the interactions and evolution of species. Science . 294: 321– 326. Google Scholar CrossRef Search ADS PubMed  Anderson MG Gill BJ Briskie JV Brunton DH Hauber ME. 2013. 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Popul Ecol . 53: 187– 193. Google Scholar CrossRef Search ADS   Welbergen JA Davies NB. 2009. Strategic variation in mobbing as a front line of defense against brood parasitism. Curr Biol . 19: 235– 240. Google Scholar CrossRef Search ADS PubMed  Welbergen JA Davies NB. 2012. Direct and indirect assessment of parasitism risk by a cuckoo host. Behav Ecol . 23: 783– 789. Google Scholar CrossRef Search ADS   © The Author(s) 2017. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Behavioral Ecology Oxford University Press

Can hosts tolerate avian brood parasites? An appraisal of mechanisms

Behavioral Ecology , Volume Advance Article (3) – Nov 22, 2017

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Abstract

Abstract Theoretical work has long stressed the need of studying in concert defenses based on resistance (i.e., mechanisms minimizing the frequency of effective parasite attacks) and tolerance (i.e., mechanisms minimizing the impact of parasites after a successful attack) to achieve a full understanding of host–parasite evolutionary dynamics. The study of tolerance can be particularly illuminating in the comprehension of avian brood parasite–host interactions because if hosts can tolerate parasitism this may resolve the long-lasting paradox of why some hosts do not reject parasite eggs despite costly parasitism. Surprisingly, although the study of host defenses against brood parasites is a hot spot for research in behavioral ecology, empirical studies of tolerance are very rare. Here, I first identify the main reasons explaining reluctance to incorporate tolerance in the study of avian brood parasite–host interactions. Tolerance defenses have been neglected because: 1) behavioral ecologists have primarily targeted on antagonistic coevolution which is most likely selected by resistance; 2) because tolerance (contrary to resistance) cannot be easily measured on host individuals; and 3) because there is a limited knowledge about the mechanisms of tolerance. In a second step, I review current evidence about tolerance in hosts and propose yet unexplored mechanisms to be studied based on parental investment theory. Finally, I propose an experimental framework based on well-established knowledge about phenotypic plasticity that can help detecting the effects of tolerance in future studies. I urge behavioral ecologists to embark on suggested mechanistic approaches to study tolerance defenses to achieve a better comprehension of avian brood parasite–host coevolution. INTRODUCTION Once faced with parasites hosts can protect themselves from their harmful effects through defenses based on resistance and/or tolerance (Svensson and Råberg 2010). Resistance involves defensive mechanisms minimizing the frequency of effective parasite attacks either by avoiding the parasite or directly attacking it (Read et al. 2008; Råberg et al. 2009), and it is operationally measured as the inverse of parasitism load (i.e., the lower the number of parasites per host, the more resistant is the host) (Råberg et al. 2009). Tolerance includes defensive mechanisms minimizing the negative impact of the parasite after a successful attack (Read et al. 2008; Råberg et al. 2009), and it is operationally measured as the slope of a regression between host fitness against parasitism load (i.e., the stepper the slope, less tolerant is the host) (Råberg et al. 2009). In other words, tolerance can be defined as the rate of change in host fitness as parasite burden increases (Råberg et al. 2009). Both resistance and tolerance are costly traits for hosts, but contrary to resistance, tolerance diminishes the impact of parasite without causing direct negative effects in the parasite (Roy and Kirchner 2000; Svensson and Råberg 2010). Due to its negative effect on parasite fitness, resistance can select for counter-defenses in parasites, which, in turn, may also select for improved host resistance, thereby resulting in a coevolutionary arms race of defenses and counter-defenses (Chisholm et al. 2006). Tolerance, however, will not select for parasite counter-defenses and rarely result in a coevolutionary arms race (Råberg et al. 2009; Svensson and Råberg 2010). Based on this difference, theoreticians have long stressed the need of considering separate costs and effects of tolerance and resistance to attain a wider comprehension of epidemiological dynamics and host–parasite coevolution (Roy and Kirchner 2000; Restif and Koella 2004; Read et al. 2008; Råberg et al. 2009; Svensson and Råberg 2010). However, studies of animal victim–enemy interactions focusing on tolerance defenses are scarce and confined to report variation in operational tolerance in infection experiments with tadpoles (Rohr et al. 2010; Sears et al. 2015), and monarch butterflies (Sternberg et al. 2013). Therefore, we know very little about the possible mechanisms of tolerance in wild animals, and understanding how victims might tolerate their enemies remains a major gap in animal ecology. The interaction between avian brood parasites and their hosts provides fascinating examples of the evolution of defenses based on resistance (Davies 2000). Interspecific brood parasitism is a reproductive strategy in which the parasitic species lays its eggs in the nest of another species, the host, which carries out the parental duties, from the incubation of eggs to chick feeding (Davies 2000; Feeney et al. 2014). Brood parasitism often imposes large costs to hosts due to egg breakage during egg laying by parasite females, rejection of host eggs and/or chicks from the nest by the parasite chick, and starvation of host chicks due to parasite chick monopolization of parental feeds (Rothstein 1990). Consequently, natural selection has favored the evolution of certain behaviors preventing cuckoo parasitism (i.e., resistance mechanisms) such as mobbing of parasites before laying (e.g., Røskaft et al. 2002; Welbergen and Davies 2009), parasite egg discrimination and rejection (e.g., Davies and Brooke 1988; Soler and Møller 1990; Avilés et al. 2010; Spottiswoode and Stevens 2010), or nestling discrimination (e.g., Langmore et al. 2003; Grim 2007; Sato et al. 2010). Resistance defenses have selected for further counter-defenses in the brood parasites, such as hawk-like cuckoo plumage to avoid host aggression (Davies and Welbergen 2008), more accurate host egg mimicry (Avilés 2008; Stoddard and Stevens 2010) or nestling phenotype matching (Langmore et al. 2011) to avoid egg or fledging rejection, resulting, in many instances, in a coevolutionary arms race (Davies 2000). Although a clear model system for the study of host defenses based on resistance, avian brood parasites may have selected for host tolerance as well (Svensson and Råberg 2010). This is so because defenses based on resistance can be costly due to recognition and rejection errors (Lotem et al. 1995), or because parasites may destroy host eggs after being aware of host resistance (i.e., mafia behavior)(Soler et al. 1995; Hoover and Robinson 2007), a scenario likely to promote the evolution of defenses based on tolerance (Svensson and Råberg 2010). In their seminal review Svensson and Råberg (2010) argued that hosts of avian brood parasites may defend against cuckoo parasites by modifying their breeding strategy to minimize the costs of brood parasitism. In theory, there are 2 ways that tolerance adaptations could work. One is a fixed response involving a genetic change in a host trait that minimizes the cost of brood parasitism, and another is plasticity in the suggested trait that turns on a tolerance mechanism only when it is needed. In the first scenario the cost of parasitism would select for changes in the life-history strategy of the host to optimize allocation over the entire life-time of the host. Fixed responses can be detectable with comparative analysis that involves comparisons among species or populations exposed to different level of parasitism. Indeed, prevailing empirical support for tolerance would come from a handful of studies comparing host life-history traits in parasitized and nonparasitized populations and showing increased clutch size (Soler et al. 2001; Cunningham and Lewis 2006) or smaller clutches combined with several nesting attempts (Petit 1991; Brooker and Brooker 1996; Anderson et al. 2013; Louder et al. 2015) in parasitized host populations. Plastic responses, however, would allow reducing the impact of a specific brood parasite in the current reproduction, but their role have been neglected despite compiling evidence that variation in phenotipic plasticity within species may strongly contribute to parasite dynamics (e.g., Gervasi et al. 2015). Previous theoretical work has suggested that tolerance and resistance in host of avian brood parasites are not mutually exclusive evolutionary responses to costly brood parasitism (Medina and Langmore 2016), and empirical evidence on magpie host parasitized by great spotted cuckoos suggest that tolerance and resistance can be present within the same population (Soler et al. 2011). Host life-history adjustments may reduce the survival of the parasite as well as mitigate the cost of parasitism when the parasite does survive, which makes difficult to ascribe them to tolerance or resistance. The fact that resistance and tolerance responses might not be mutually exclusive components of host defense against brood parasites has not been previously considered, but may have depth implications for the study of host tolerance, which I describe more fully below. Svensson and Råberg (2010) stressed that tolerance is likely to play a fundamental role in the evolutionary dynamic of brood–parasitic interactions because whether a host can tolerate cuckoos, this may help explaining the classic paradox of why some hosts exhibit a noticeable absence of resistance defenses despite costly parasitism (see also Kilner and Langmore 2011). The theoretical consequences of considering tolerance defenses have been recently expanded in 2 review articles. Medina and Langmore (2016) have stressed that whether a host resist or tolerate a brood parasite will determine the chance of detecting antagonistic coevolution (i.e., coevolution will be a less likely outcome when the hosts tolerate). Moreover, Soler and Soler (2017) have argued that the diversification rate of avian brood parasites should be lower whether host defenses are based on tolerance. Surprisingly, despite recent advances in theoretical grounds about consequences of considering tolerance in the study of cuckoo–host interactions, we still have very few examples of tolerance defenses, and a very poor understanding of the possible mechanisms behind tolerance defenses (Medina and Langmore 2016). Identifying the mechanistic basis of tolerance remains a logical next step as it will help balancing currently disproportioned theoretical and empirical evidence to provide a more integrative framework for the study of cuckoo–host evolutionary dynamics. Hence, here I will focus on a fundamental issue that was not treated in depth in previous reviews, namely the study of the mechanistic basis of tolerance defenses in hosts of avian brood parasites. In a first step I will identify the main reasons explaining reluctance to incorporate tolerance in empirical studies of cuckoo–host interactions. In a second step I will thoroughly review current evidence of tolerance mechanisms in hosts of avian brood parasites and propose yet unexplored alternative mechanisms to be investigated based on parental investment theory. Finally, I will propose a novel experimental framework based on well-established knowledge about phenotypic plasticity that can help detecting the subtle effects of tolerance in future studies of avian brood parasitism. WHY DOES RELUCTANCE TO STUDY TOLERANCE PERSIST? Despite recent theoretical advances in the understanding of the evolutionary consequences of considering tolerance defenses (Svensson and Råberg 2010; Feeney et al. 2014; Medina and Langmore 2016; Soler and Soler 2017), yet the concept and the study of tolerance have only been minimally integrated in the study of the evolutionary interactions between avian brood parasites and their hosts. In the only explicit test of the adaptive value of tolerance in a brood parasitic system, Soler et al. (2011) found that operational tolerance (i.e., the slope of the regression between the number of cuckoo eggs in a clutch and the number of fledglings produced) in the European Magpie (Pica pica), host of the great spotted cuckoo (Clamator glandarius), differed among host populations. In addition, tolerance was found to be larger in magpie populations suffering high levels of parasitism, suggesting that it may have evolved as an adaptive response to cuckoo parasitism in magpies (Soler et al. 2011). Also, and based on a modeling approach, Takasu and Moskat (2011) concluded that host tolerance together with host immigration may explain the long-term persistence of heavy cuckoo parasitism on Hungarian great reed warblers (Acrocephalus arundinaceus). Although these studies provide some evidence of the adaptive value of tolerance in compensating brood parasitism costs, the mechanistic basis of tolerance defenses against avian brood parasites remains elusive. Indeed examination of published items in the WEB OF SCIENCE reveals a lack of studies considering the role of host defenses based on tolerance. Only 6 out of 250 papers published after publication of the Svensson and Råberg (2010) review including the search term “avian brood parasitism” either in the title, abstract or keywords also included the term “tolerance defense”, representing a meagre 0.02% of all studies (search performed on 9 February 2017). Below I identify 3 mutually nonexclusive reasons that may help explaining this bias against the study of tolerance defenses. Historical reasons Tolerance against parasites do not generally result in coevolution (Svensson and Råberg 2010), whereas avian brood parasitism has largely been recognized as an ideal model system for studying antagonistic coevolution (Rothstein 1990; Davies 2000; Kilner and Langmore 2011; Soler 2014). As a consequence, evolutionary biologists have largely targeted the study of resistance which is likely to select for new forms of counter-resistance in brood parasites, which may subsequently select for more elaborated forms of host resistance. Hence, an impressive body of empirical evidence about host resistance mechanisms and parasite trickeries has been accumulated in different avian brood–parasite–host systems, whereas evidence for tolerance is only very recent and anecdotal. Mistreatment of tolerance may also be due to the fact that most early seminar empirical work was based on the interaction between the evicting common cuckoo and their hosts (e.g., Davies and Brooke 1988; Lotem et al. 1995). It is hard to imagine how tolerance may evolve if the cuckoo chick evicted all the host eggs or nestlings from the nest. Achieving a better knowledge of the full array of tolerance mechanisms exhibited by different hosts, and, of the evolutionary consequences of having evolved tolerance for the dynamics of their interactions with their avian brood parasites will probably help to change the misconception that avian brood parasite–host systems mostly serve to study coevolution. Operational tolerance is a feature of populations not of individuals Quantifying tolerance is a major issue in studies of animal victim–enemy interactions in general (Råberg et al. 2009), and of avian brood parasite–host interactions in particular (Medina and Langmore 2016). Two main approaches have been proposed, both requiring studying the fitness outcome of avian brood parasite–host interactions in several populations (reviewed in Medina and Langmore 2016). On one hand, tolerance can be operationally estimated as the reaction norm of host fitness against level of parasitism, the steeper the slope of the regression is, the lower the tolerance (“range tolerance” sensu Medina and Langmore 2016; Svensson and Råberg 2010). Alternatively, host fitness could be compared in 2 populations exposed to the same level of parasitism, the one with the highest fitness being the more tolerant (“point tolerance” sensu Medina and Langmore 2016). These approaches, however, may lead to flawed conclusions about the role of tolerance if the populations a priori differed in the qualities of the hosts, because, in such a case, differences in fitness between the populations would have nothing to do with defenses against brood parasites (see discussion in Svensson and Råberg 2010). Calculation of operational tolerance is a prerequisite for studying the adaptive value of host defenses against brood parasites (e.g., Soler et al. 2011), but mechanisms cannot be elucidated based on operational tolerance and tolerance mechanisms need to feasibly underlie patterns of operational tolerance. In addition range and point tolerance do not allow identifying whether individual hosts within parasitized population may differ in tolerance as they do in resistance. Previous theoretical work has suggested that the evolution of tolerance defenses may limit the evolution of resistance (Svensson and Raberg 2010), which can be tested by assessing if tolerance and resistance are correlated across host individuals within a given population. I argue that reluctance to study tolerance is partly due to the fact that evolutionary biologists working on brood parasitism have not been able to feasibly envisage how to test for tolerance at the individual level, and that a more mechanistic conception of the study of tolerance defenses may contribute to alleviate this issue (see below). Mechanisms of tolerance are unknown and evidence for true tolerance is not conclusive We have a very poor understanding of tolerance mechanisms in hosts of avian brood parasites, possibly due to the fact that defenses based on tolerance are much more subtle and, thus, less detectable than those based on resistance. In Table 1, I have summarized published studies where a mechanism of tolerance to brood parasites was reported by Medina and Langmore (2016), as well as other previously noncited studies that may also suggest host tolerance. Aiming to discern whether costs of brood parasitism may relate to a particular tolerance mechanism, I have classified these studies based on whether parasites share the nests with host offspring or not. I also have reported whether evidence of a resistance mechanism exists for that host, so that I can tentatively assess if there exists a relationship between resistance and tolerance mechanisms. Table 1 Evidence of mechanisms of tolerance against avian brood parasites Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  *Rejection behavior has not been studied. View Large Table 1 Evidence of mechanisms of tolerance against avian brood parasites Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Host  Brood parasite  Parasite share nest with host young  Approach for inference  Result  Tolerance mechanism  Reported resistance (rejection)  Alternative explanation to tolerance  Reference  Pica pica  Clamator glandarius  Yes  Within population -correlative  Host clutch size was positively related to host breeding success in parasitized Magpies  Increased clutch size  Yes  High quality magpies are better parents or preferred by cuckoos  Soler et al. (2001)  Pica pica  Clamator glandarius  Yes  Across populations- correlative  Sympatric magpie populations had significantly larger clutches and smaller eggs than allopatric populations  Increased clutch size  Yes  Cuckoo exploit magpies population with particular breeding parameters  Soler et al. (2001)  Psarocolius montezuma  Scaphidura oryzivora  Yes  Within population- correlative  Two-egg nests were more likely to produce one fledging than one- egg nests.  Increased clutch size  Yes  1)High quality host are better parents. 2)Host clutch size and brood success are age dependent  Cunningham and Lewis (2006)  Malurus splendens  Chalcites basalis  No  Within population- correlative  Parasitized birds laid more clutches than those not parasitized.  Decreased clutch size, Multiple brooding  No  Cuckoo exploit individuals with particular breeding parameters  Brooker and Brooker (1996)  Gerygone igata  Chalcites lucidus  No  Across- population - correlative  Populations suffering high parasitism have more nesting attempts  Multiple brooding  No  Cuckoos exploit population with particular breeding parameters  Anderson et al. (2013)  29 host species  Molothrus ater  Yes  Comparative study  Old hosts have lower clutch size and larger number of breeding attempts than new hosts  Decreased clutch size, Multiple brooding  Some species  Cowbirds exploit species with particular breeding features  Hauber (2003a)  134 host species  Molothrus ater  Yes  Comparative study  Species suffering high parasitism have shorter nesting periods  Faster nestling growth  Some species  Cowbirds exploit species with shorter nesting periods  Remeš (2006)  Melospiza melodia  Molothrus ater  Yes  Within population- correlative  Song sparrows that were parasitized one or more times during a breeding season raised as many young as females that were not parasitized  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Smith (1981)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative  Females that accepted parasitism and produced 2 broods had higher fitness than females that raised only one unparasitized brood  Multiple brooding  No  Cowbirds exploit individuals with particular breeding features  Petit (1991)  Protonotoria citrea  Molothrus ater  Yes  Within population- correlative and experimental  Experimentally parasitized warblers increased double- brooding behavior  Multiple brooding  No  Cowbirds are manipulating hosts to increase their fitness  Louder et al. (2015)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  *  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  Setophaga ruticilla  Molothrus ater  Yes  Within population- correlative  Host eggs in naturally parasitized nests had elevated yolk testosterone  Increased maternal androgens in eggs  Yes  Cowbirds exploit individuals with particular breeding features  Hahn et al. (2017)  *Rejection behavior has not been studied. View Large Examination of these 10 studies reveals that most evidence of tolerance came from a handful of studies reporting a modification of the host breeding strategy in parasitized nests (9 of 10 studies cited in Table 1). Specifically, changes in host breeding strategy may entail increasing (reported in 2 studies in 2 different brood parasite-host systems) or decreasing clutch size (reported in 2 studies, one with a host of one Australian cuckoo and another comparative study based on 29 brown-headed cowbird Molothrus ater hosts), increased proneness to multiple brooding (i.e., reported in 6 studies in several hosts of the brown-headed cowbird, but also in one host of one Australian cuckoo), increased maternal investment in host eggs (reported in one study with 2 brown-headed cowbird hosts) or acceleration of host nestling development (reported in one comparative study with 134 brown-headed cowbird hosts) (Table 1). Thus, except for 2 studies that reported an increase of clutch size (Table 1), all other sources of evidence would concur with a general host strategy of reducing parasitism costs by shortening and fractioning host reproductive events within a single season. It has been previously suggested that whether hosts will opt to increase or reduce their breeding investment in currently parasitized broods might ultimately depend on the extent of parasitism costs (Medina and Langmore 2016). For instance, where brood parasites are raised together with host nestlings, hosts may diminish the relatively small damage caused by laying brood parasites through increasing their clutch size. Laying extra eggs may thus function as an insurance strategy against this small damage. This appears to be the case of the Montezuma Oropendolas Psarocolius montezuma parasitized by the Giant cowbird Scaphidura oryzivora (Cunningham and Lewis 2006) (Table 1). The insurance hypothesis, however, would not apply to Eurasian magpie parasitized by the Great spotted cuckoo (Soler et al. 2001), because once the great spotted cuckoo nestling hatches it will invariably starve all the host offspring, and thus the fitness benefits of laying an extra eggs will disappear. In contrast, where costs of parasitism are large because host nestlings or eggs are evicted by the parasite, it would be advantageous for the hosts to reduce their clutches and to increase the number of broods to raise per breeding season, as it was reported for Splendid fairy-wren Malurus splendens parasitized by Horsfield’s Bronze-cuckoos Chalcites basalis in Autralia (Brooker and Brooker 1996) and for Gray warblers Gerygone igata parasitized by Shinning Bronze-cuckoos Chalcites lucidus in New Zealand (Anderson et al. 2013). However, multiple brooding linked to parasitism has also been reported in several hosts of brown headed cowbirds where parasites are raised together with host nestlings (Smith 1981; Petit 1991; Louder et al. 2015). Also, comparative evidence has shown that host species largely exposed to cowbird parasitism in North America have lower clutch sizes and larger number of breeding attempts than new hosts (Hauber 2003a). In a second comparative study, Remeš (2006) found that brown-headed cowbird host species suffering high rate of parasitism showed shorter nesting periods, which suggests that faster growing and shorter incubation may have been selected in evolutionary time as tolerance mechanisms to lessen the costs of cowbird parasitism. A global interpretation of these findings in terms of costs of parasitism, however, might be problematic as currently assumed low costs of parasitism in some systems may indeed reflect the effect of tolerance selected in the pass. Evidence of tolerance has accumulated in host species that do not reject parasitic eggs at all, as in some hosts of Australian Chalcites species or in brown-headed cowbird hosts, as well as in hosts that can reject model eggs (Table 1). Therefore, it seems that, in general, the evolution of resistance would have not limited the evolution of tolerance mechanisms in hosts of avian brood parasites. It must be highlighted, however, that although these studies provide tentative evidence of host tolerance in several different systems, none was specifically designed to study tolerance defenses. Indeed, a comprehensive analysis of the study designs in these studies reveals that in all cases one or several alternative explanations to the hypothesis of tolerance can account for the patterns found (see Table 1). In particular, selection by avian brood parasites of host individuals, populations and species with particular breeding attributes is a likely alternative explanation that held possible for all these studies (Table 1). Moreover, previous theoretical and empirical work has interpreted changes in host life-history traits in response to brood parasitism as evidence of tolerance (Svensson and Raberg 2010; Soler et al. 2011; Medina and Langmore 2016), which may have help expanding the false impression that there are distinct resistance responses and distinct tolerance responses toward brood parasites. This may be the case for some host responses like egg rejection, which can unambiguously be ascribed to resistance. However, most of host life-history adjustments in response to parasitism (e.g., hatch patterns or clutch size adjustments), which currently constitutes the basis of the empirical support for tolerance (see above), could in theory involve aspects of both—reduce the survival of the parasite (i.e., resistance) as well as mitigate the costs of parasitism when the parasite does survive (i.e., tolerance) (see above). Summing up, current evidence of tolerance is still inconclusive and very scarce and further experimental studies controlling for possible confounding variable are needed to critically assess to what extent hosts of avian brood parasites may compensate for the costs of raising parasitic chicks. An appraisal of mechanisms favoring cuckoo tolerance It is known that female birds may modify their reproductive investment affecting offspring phenotype in ways that increase female fecundity in response to changes in the environmental conditions (maternal effects sensu Mousseau and Fox 1998). Once successfully parasitized, hosts may potentially buffer the harmful effect of parasitism through modification of an array of behavioral, life-history and physiological traits, most of them never studied in the frame of tolerance defenses. I identify several different host traits that can potentially be modified after parasitism through pre- and postnatal maternal effects (Figure 1) and that may provide fitness benefits for the hosts worth exploring in future experiments. Figure 1 View largeDownload slide Measurable hosts traits that may potentially suggest evidence of a tolerance mechanism in relation to host reproductive cycle. Hosts can plastically modify behavioral, life-history and physiological traits after a parasitism event. Figure 1 View largeDownload slide Measurable hosts traits that may potentially suggest evidence of a tolerance mechanism in relation to host reproductive cycle. Hosts can plastically modify behavioral, life-history and physiological traits after a parasitism event. Experimental work has shown that birds have the potential to plastically adjust their reproductive behaviors (i.e., including incubation and feeding behaviors) in response to changes in risk of nest predation (Fontaine and Martin 2006; Martin and Briskie 2009). Also, in the context of brood parasitism, experiments have shown that in American coots Fulica americana parents are able to modify the intensity and direction of incubation (Lyon 2007; Shizuka and Lyon 2011). Therefore, a promising field to understand tolerance deeply in systems where host offspring is raised together with a parasite, is studying if parasitized individuals may modify their reproductive behaviors once parasitized to minimize the costs of parasitism. It is well known that through the modification of their incubation pattern, birds are able to modify the degree of hatching asynchrony of their clutches (reviewed in Magrath 1990). Moreover, comparative and experimental evidence suggest that hatching synchronously reduces the costs of parasitism in hosts of brown-headed cowbirds (Hauber 2003b). Thus, it can be hypothesized that hosts may minimize the losses of nestlings to parasitic chicks by producing synchronous broods. Another possibility explored theoretically is that host parents increased their feeding effort in parasitized nests to minimize the chance of starvation of their own offspring in their competition with the parasitic chick (Holen and Johnstone 2007). However, it could also be predicted that parents opted to reduce their feeding effort in parasitized nests saving energy for future breeding attempts (see Figure 2). Although expectations about how hosts may modify their behaviors to minimize the cost of raising a parasitic chick may ultimately depend on the tolerance strategy of the species (see Figure 2), the study of plasticity in reproductive behaviors in response to brood parasitism may open new avenues in our understanding of host tolerance against brood parasites. Figure 2 View largeDownload slide Host tolerance strategy in relation to brood parasitism virulence. Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impact on host fitness through outcompeting or complete eviction of their offspring. Alternatively, host may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with the host offspring. Tentative expectations of how host may modify behavioral, life-history and physiological traits in response to brood parasitism depending of one tolerance strategy or another are presented. Figure 2 View largeDownload slide Host tolerance strategy in relation to brood parasitism virulence. Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impact on host fitness through outcompeting or complete eviction of their offspring. Alternatively, host may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with the host offspring. Tentative expectations of how host may modify behavioral, life-history and physiological traits in response to brood parasitism depending of one tolerance strategy or another are presented. Several sources of evidence have shown that birds have the potential to plastically adjust their life-history traits (i.e., egg size and clutch size) in response to increased perceived predation risk (Lima 2009; Martin and Briskie 2009; LaManna and Martin 2016). In addition, experimental studies have shown that in birds, females have the potential to modify their investment on eggs (i.e., hormone composition and egg size) in response to a sudden change in environmental conditions during laying (Saino, Romano, Caprioli, et al. 2010; Saino, Romano, Rubolini, et al. 2010; Parejo et al. 2012). Therefore, in host species in which the offspring is raised together with a parasitic chick it might be advantageous to parasitized hosts increasing the size of their eggs, as it positively relates with the size and competitiveness of nestlings (Krist 2011). However, where parasitic chicks are raised alone, or where an increase in egg size does not reverse the highest competitiveness of the parasitic nestlings over the host ones, host could opt to save as much energy as possible for future reproductive events by reducing eggs and clutches. It is, thus, critical considering that in species where multiple brooding is possible, the study of tolerance should embrace all possible breeding attempts as the benefits of reducing the investment after being parasitized (i.e., a prerequisite for tolerance being detected) might only be detected by considering together host investment in current versus future breeding attempts. Finally, another poorly explored possibility is that tolerance primarily comes by physiological maternal effects. Hahn et al. (2017) have recently found that eggs of the American redstart Setophaga ruticilla and the Red-eye vireo Vireo olivaceus exhibited higher levels of yolk testosterone in nests that were parasitized by the brown-headed cowbird than in nonparasitized nests. Given compelling evidence showing that elevated levels of yolk testosterone in the eggs accelerate embryo development and nestling growth, shorten the incubation period and increase the intensity of begging behaviors in birds (Schwabl 1993, 1996), these findings are consistent with the possibility that hosts, through maternal effects, may modify their offspring phenotype to diminish the costs of sharing the nest with a parasite chick. The interpretation of Hahn et al. (2017)’s results is difficult, however, because hormone levels in the eggs were estimated on entire clutches and therefore it cannot be discarded that cowbirds were selecting nests by host qualities related to hormone levels. Another simple alternative hypothesis would be that parasitism is associated with aggressive encounters with the brood parasite, and that the elevated testosterone level in eggs is a simple side-effect of such an increase in aggression and testosterone in females. Moreover, some studies have found a relationship between maternal yolk hormones in the eggs and sex determination (Petrie et al. 2001; but see Eising et al. 2003), raising the yet neglected possibility that hosts may bias the sex of their offspring toward the more competitive sex, or the most dispersive one when being parasitized. Therefore, the study of maternal yolk hormones in the eggs in response to parasitism and of the possible effects of these hormones on the array of behavioral (i.e., begging intensity), life-history (i.e., growth rates) and physiological (i.e., nestling immunity) host traits likely related to fitness appear obvious next steps in our understating of tolerance mechanisms. It must be highlighted, however, that many of the putative mechanisms for host tolerance I have here described might potentially impose harm on the brood parasite and thus may lead to an evolutionary arms race of attack and host resistance. For example, hosts may attempt to synchronize hatching of the clutch and the parasite’s best response would then be to shorten its incubation period to get a head start and regain its competitive advantage. Testing if parasite fitness is decreased in response to the change in a host trait is a fundamental step to discard that “tolerance” leads to an escalation of the costs of parasitism and a likely switch to resistance in the host. Strategies of tolerance I envisage 3 possible host tolerance strategies depending on how much brood parasitism impacts on host fitness (see Figure 2). Each one has particular expectations regarding how behavioral, life-history and physiological traits of hosts should differ between parasitized and unparasitized nests in a population, which I have summarized in Figure 2. Whenever parasitism imposes high costs to hosts, that is, when differences in size between host and parasite nestlings raised together are large in favor of the parasitic nestling and, in systems where parasites are raised alone by the hosts, it may pay hosts following a strategy of “saving energy” for future breeding attempts through a reduction of current reproductive investment. The frequently reported observation that parasitized nests or populations of some brown-headed cowbird hosts, but also some Australian cuckoo hosts (Table 1), have lower clutch sizes that nonparasitized nests may suggest that the “saving energy” strategy could be a widely spread evolutionary solution to counteract costly brood parasitism. Besides reducing clutch size, hosts may save energy reducing egg size or the amount of costly maternal hormones deposited in their eggs, which may bias their offspring sex-ratio towards producing the less energetically demanding sex (Figure 2). The “save energy” strategy may also imply a lower attendance of nests during incubation and nestling provisioning in parasitized nests, which may potentially result in larger hatching asynchrony or decelerated growing (Figure 2). These possibilities have not yet been investigated. A second possible tolerance strategy when facing highly virulent brood parasites that impose intermediate cost is to shorten as much as possible the development of the offspring to increase the chance of having another breeding attempt in the season. Shortening might be achieved through prenatal maternal effects. For instance, female hosts may modify the amount of androgens in the eggs in parasitized nests (Hahn et al. 2017). High level of steroid hormones in the egg yolk accelerates embryo development and growth rates, and favors a more vigorous begging of nestlings, which may also induce higher levels of parental provisioning by hosts (Figure 2). Also, through modification of hormone levels in the eggs hosts may potentially bias their offspring sex-ratio towards the sex with a faster development (Figure 2). Behavior may also play a role in the “shortening” strategy. For instance, hosts may intensify their incubation promoting lower hatching asynchrony and thus the shortening of the nestling dependence period if food conditions are good enough and parents can provide enough feedings (Figure 2). Finally, shortening might also arise from postnatal parental effects if parents increased their provisioning rate when parasitized irrespective of intensity of begging display (Figure 2). It must be considered that whether a host opt by a “save energy” or a “shortening” strategy is likely depending on environmental conditions. The “shortening” strategy implies higher breeding investment in the short time than the “save energy” strategy, and therefore will be a most likely tolerance strategy where hosts faced good environmental conditions. Also the pace of life of hosts is likely to determine the chance of these 2 strategies, with “slow-paced” hosts with slow development rates and long life spans being less able to opt by a “shortening” strategy than “fast-paced” hosts (e.g., Sears et al. 2015) Alternatively, where differences in size between parasite and host nestlings are small, and therefore where parasitism is not that costly, it may pay hosts increasing their breeding investment to enhance the competitiveness of their offspring in the battle with parasitic nest-mates. So far evidence for this “preparing for battle” strategy is scant, and indirectly came from a single study showing increased level of maternal androgens in the eggs of American redstart and red-eyed vireo nests parasitized by brown-headed cowbirds (Hahn et al. 2017). In these 2 species, a proportion of host nests fledge one or more host nestlings together with the cowbird fledging. Therefore, it could be argued that in parasitized nests parents may modify the amount of maternal androgens in the eggs aiming to accelerate growing and begging of their offspring, as this may increase their survival. In the same vein, in sexually dimorphic hosts, it would be expected that parent may bias the sex of their offspring toward the bigger sex, as this would have greater chance of not being outcompeted by the parasite nest-mate. It must me considered, however, that the “preparing for battle” strategy could also be a resistance strategy if the increase in competitiveness of host chicks impacts the parasite chicks. Therefore, it is critical to assess whether the host responses may harm the parasites to ensure that we are dealing with a true tolerance strategy (see below). The “preparing for battle” and the “shortening” strategies have identical expectations for growth rates and begging displays in parasitized nests (see Figure 2). This is so because a faster development of the offspring will give host parents more chance of having a second reproduction in the same season, but also will increase the survival of their offspring through early hatching and a more effective competition for parental food delivery with the parasite nestlings. Twofold benefit of a faster development is perhaps behind the general pattern of faster growth rate reported among hosts suffering higher level of parasitism in cowbird hosts Remeš (2006). However, the 2 strategies can be differentiated in the wild because they have different expectations regarding egg size and clutch size that are likely to increase in parasitized nests under a “preparing for battle” strategy. As reported above, laying extra eggs may function as an insurance strategy against small damage (Cunningham and Lewis 2006). Also larger eggs will produce bigger nestlings that will compete better with parasite nest-mates. Sex-ratio expectations also differ for the 2 strategies, being the more competitive sex (i.e., the bigger) over the one with a faster development, the more likely selected under a scenario of nestling competence. A reaction norm approach for the study of tolerance Tolerance could be achieved through plasticity in resource allocation in response to brood parasitism. Phenotypic plasticity is the property of a genotype to produce different phenotypes in response to different environmental conditions (Pigliucci 2005). Plasticity in resource allocation in response to environmental stress is among the most commonly studied tolerance mechanism in plants (reviewed in Strauss and Agrawal 1999), although their role is still poorly understood in animal-enemy interactions. Several sources of empirical evidence have shown that variable risk of predation may induce plasticity in life history, behavioral and physiological traits in birds (Martin and Briskie 2009; Lima 2009a; LaManna & Martin 2016). Also, previous experimental studies have suggested that hosts of avian brood parasites may respond plastically to risk of parasitism through changes in defenses based on resistance (Davies and Brooke 1988; Moksnes et al. 1993; Welbergen and Davies 2012). Moreover, a recent study has relied on the reaction norm approach to estimate individual tolerance in the Soay sheep (Ovis aries) in response to a gastrointestinal nematode parasite (Hayward et al. 2014). However, although it should be at the core of the study of tolerance mechanisms, it remains unstudied whether variable levels of brood parasitism may induce plastic changes in life-history, behavioral or physiological traits of their hosts that may help them to minimize the harmful effects of parasitism. I argue that adopting a phenotypic plasticity framework to simultaneously study host traits and fitness as individual-specific reaction norms related to intensity of parasitism is critical to achieve a full understanding of tolerance mechanisms and the adaptive value of tolerance. In this context, the reaction norm would be the repertoire of phenotypic and fitness responses of a host genotype along a gradient of brood parasitism, and hence a property of individuals. I have summarized in Figure 3 how to study host tolerance to brood parasitism based on reaction norm approach (Figure 3). Figure 3 View largeDownload slide A reaction norm approach for the study of tolerance mechanisms in hosts of avian brood parasites. The figure shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the individual reaction norm in 1) resource allocation and 2) fitness of these 2 individuals. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In panel a, slope of the individual 1 is stepper than slope of the individual 2, implying that individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than individual 2. In panel b, however, slope of the relationship between parasitism level and fitness is stepper for individual 2 than for individual 1, meaning that the former is the less tolerant. Figure 3 View largeDownload slide A reaction norm approach for the study of tolerance mechanisms in hosts of avian brood parasites. The figure shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the individual reaction norm in 1) resource allocation and 2) fitness of these 2 individuals. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In panel a, slope of the individual 1 is stepper than slope of the individual 2, implying that individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than individual 2. In panel b, however, slope of the relationship between parasitism level and fitness is stepper for individual 2 than for individual 1, meaning that the former is the less tolerant. Figure 3 shows the simple case of a host population composed of 2 individuals exposed to different intensities of parasitism. The lines would represent the reaction norm in 1) resource allocation and 2) fitness of each individual host. Lines have a slope that can be used to measure the degree of plasticity and tolerance. In the panel a, the slope of the individual 1 is stepper than the slope of the individual 2, meaning that the individual 1 is more plastic (i.e., it can modify more its phenotype in relation to parasitism) than the individual 2. In the panel b, however, the slope of the relationship between parasitism level and fitness is steeper for the individual 2 than for the individual 1, meaning that the former is the less tolerant. The reaction norm approach described in the Figure 3 contributes to the study of tolerance mechanisms in at least 3 fundamental ways: 1) First, it allows studying tolerance defenses at the individual level, and, therefore, to differentiate between more or less tolerant hosts within a population, such as it has been largely done for defenses based on resistance (Figure 3). Hence, this approach place tolerance and resistance at the same level and provides an unique opportunity for testing whether host plasticity in resource allocation (i.e., tolerance) may have limited the evolution of resistance defenses as some theoretical models have proposed (e.g., Svensson and Råberg 2010). 2) Second, the combined visualization and analysis of host individual reaction norms in phenotype and in fitness in relation to parasitism level provides a unique opportunity for identifying the mechanistic basis behind tolerance defenses. Moreover, this will allow testing the very relevant question of whether the most plastic host individuals are the most tolerant as well. 3) Third, this approach allow quantifying genetic variation in tolerance in the population based on variation in slopes and height of all fitness reaction norms of the individuals in the population (e.g., Ghalambor et al. 2010), which is necessary in any attempt of quantifying the genetic basis of differences in tolerance defenses among populations and species. HOW TO STUDY MECHANISMS OF TOLERANCE IN THE WILD? Two main kinds of studies at the population level may help to shed light on the mechanistic basis of tolerance: Longitudinal studies on marked host individuals Several seminal studies in the field of phenotypic plasticity have acknowledged that the reaction norm is ultimately a property of genotypes (e.g., Stearns 1989; Agrawal 2001; Ghalambor et al. 2010). Therefore, to study host tolerance defenses based on the reaction norm paradigm one would need to sample behavioral, life-history and physiological traits and fitness of individual hosts along a gradient of parasitism. In practice, this would mean marking host individuals in a population and monitoring every breeding attempt in their life. Moreover, for every breeding attempt, it should be necessary to record the intensity of parasitism (i.e., number of parasite eggs found in the nest), the final reproductive outcome (i.e., a fitness correlate), and to quantify all possible life-history, behavioral and physiological traits likely to play a role as tolerance mechanisms listed in Figure 1. Finally, an additional thing to measure would be if and how much variation in host traits thought to be mechanism of tolerance also impact the success of the brood parasite. If the responses harm the parasite then the trait may actually be a subtle form of resistance rather than tolerance. The longitudinal approach has been used by Hayward et al. (2014), who applied random regression models to longitudinal data of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. This study revealed that individuals greatly differ in tolerance, and that the more tolerant ones produced more offspring over the course of their lives (Hayward et al. 2014). A recent longitudinal study in magpie hosts parasitized by the great spotted cuckoo in Spain has shown the importance of sampling several times across the lifetime of individuals to attain a reliable assessment of defenses based on resistance (Molina-Morales et al. 2014). Extending studies like this to include life-history, behavior and physiological features of hosts appears a logical next step to achieve a full understanding of defenses based on tolerance. Experimental studies Plasticity in resistance defenses has been widely studied through manipulation of perceived risk of parasitism at the host nest during laying and incubation (Davies and Brooke 1988; Moksnes et al. 1993; Welbergen and Davies 2012). A similar experimental approach combined with the quantification of life-history, behavior and physiological responses of the hosts may greatly enhance our understanding of the role of plastic responses and tolerance defenses against brood parasites. This approach would require having previous understanding of the natural history of the system and the physiological mechanisms that underlie the behavioral responses, as without this it would be possible to do experiments that yield negative results, which can lead to the incorrect conclusion that nothing interesting is going on. Another possibility is manipulating the level of parasitism itself in host nests and assessing the direct effect of parasite removal on host physiology, behavior, and fitness. Experimental removal of parasites has now successfully been used to study tolerance to ectoparasites in a study on mockingbirds Mimus parvulus and medium ground finches Geospiza fortis parasitized by the nest fly Philornis downsi in the Galapago islands (Knutie et al. 2016). Interestingly, parasitized mockingbird nestlings begged more than nonparasitized mockingbird nestlings, which induced higher parental provisioning that compensated for parasite damage. In this example, however, begging is a trait that happens to provide tolerance to mockingbirds but that was not evolved to deal with the cost of the nest fly which was a novel disease (Knutie et al. 2016). Tolerance traits should be those evolved specifically to deal with the costs of the parasite (Read et al. 2008; Råberg et al. 2009), hence mockingbirds can be considered as a tolerant species although this would not constitute an example of the evolution of tolerance. As noted above, it can be difficult to assign host responses to brood parasitism to resistance or tolerance. Therefore, in combination with manipulations of parasitism (i.e., either risk or true) and the assessment of host responses, it is critical to assess whether host responses (i.e., changes in life-history, behavioral and physiological traits) impacts the parasite. If the trait affects the parasite then it is at least in part resistance, and it might be hard to make the case for tolerance. However, if the trait improves host fitness without impacting the parasite, then it is clearly tolerance. Experiments could get at this for some putative tolerance traits: for example, alter hatching synchrony or clutch size and look at whether parasite fitness is decreased, host fitness is increased or both. Summing up, a logical experimental pathway for the study of tolerance defenses would be first identifying candidate host traits playing a role in tolerance throughout manipulations of parasitism load, and, secondly, the manipulation of those host traits and the study of fitness consequences for the host and parasite, which would help assessing whether host responses are due to tolerance or resistance. CONCLUSIONS Identifying the mechanistic basis of tolerance defenses remains a major challenge in the study of brood parasite–host interactions as it will help merging currently separated theoretical and empirical evidence to provide a more integrative framework for the study of cuckoo–host evolutionary dynamics. Current evidence of tolerance is inconclusive and scarce and experimental studies controlling for possible confounding variables are needed to critically assess to what extent hosts of avian brood parasites may compensate for the costs of raising parasitic chicks. Once parasitized, hosts may buffer the harmful effect of parasitism through modification of an array of behavioral, life-history and physiological traits, most of them never studied in the framework of tolerance defenses. Hosts may tolerate brood parasites using different strategies of breeding investment: Hosts may more likely opt for saving energy or shortening their reproduction when parasitism severely impacts on host fitness. Alternatively, hosts may opt to increase their breeding investment to enhance the competitiveness of their offspring in nests where virulence is lower and the parasite is raised together with host offspring. Adopting a phenotypic plasticity framework to simultaneously study host traits and fitness as individual-specific reaction norms related to intensity of parasitism is critical to achieve a full understanding of tolerance mechanisms, and the adaptive value of tolerance. FUNDING I was supported by the Spanish Ministry of Economy and Competitiveness during the redaction of this manuscript (Projects CGL2014-56769-P). I am grateful to D. Parejo, J.G. Martínez, and M. Exposito-Granados for very helpful discussion during the elaboration of the manuscript. I am also deeply grateful to L Simmons by inviting me to write this review and to B. Lyon, and 2 anonymous reviewers for very constructive comments and suggestions. REFERENCES Agrawal AA. 2001. Ecology - Phenotypic plasticity in the interactions and evolution of species. Science . 294: 321– 326. Google Scholar CrossRef Search ADS PubMed  Anderson MG Gill BJ Briskie JV Brunton DH Hauber ME. 2013. 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Behavioral EcologyOxford University Press

Published: Nov 22, 2017

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