Mhc haplotype H6 is associated with sustained control of SIVmac251 infection in Mauritian cynomolgus macaquesMee, Edward T.; Berry, Neil; Ham, Claire; Sauermann, Ulrike; Maggiorella, Maria T.; Martinon, Frédéric; Verschoor, Ernst J.; Heeney, Jonathan L.; Le Grand, Roger; Titti, Fausto; Almond, Neil; Rose, Nicola J.
doi: 10.1007/s00251-009-0369-8pmid: 19337730
The restricted diversity of the major histocompatibility complex (MHC) of Mauritian cynomolgus macaques provides powerful opportunities for insight into host-viral interactions and cellular immune responses that restrict lentiviral infections. However, little is known about the effects of Mhc haplotypes on control of SIV in this species. Using microsatellite-based genotyping and allele-specific PCR, Mhc haplotypes were deduced for 35 macaques infected with the same stock of SIVmac251. Class I haplotype H6 was associated with a reduction in chronic phase viraemia (p = 0.0145) while a similar association was observed for H6 class II (p = 0.0063). An increase in chronic phase viraemia, albeit an insignificant trend, was observed in haplotype H5-positive animals. These results further emphasise the value of genetically defined populations of non-human primates in AIDS research and provide a foundation for detailed characterisation of MHC restricted cellular immune responses and the effects of host genetics on SIV replication in cynomolgus macaques.
Identification of Igσ and Igλ in channel catfish, Ictalurus punctatus, and Igλ in Atlantic cod, Gadus morhuaEdholm, Eva-Stina; Wilson, Melanie; Sahoo, Manoranjan; Miller, Norman; Pilström, Lars; Wermenstam, Niklas; Bengtén, Eva
doi: 10.1007/s00251-009-0365-zpmid: 19333591
Immunoglobulin light (IGL) chain genes encoding σ and λ from channel catfish, Ictalurus punctatus, and λ from Atlantic cod, Gadus morhua, were identified by mining of expressed sequence tag databases, 5′-RACE and RT-PCR protocols. cDNAs for each of these IGL chains encode typical variable (V), joining (J), and constant (C) regions and Southern blot analyses and genomic sequencing show that genes encoding these isotypes, like other teleost IGL genes, are found in a cluster organization of one or two V gene segments, followed by single J and C gene segments, all in the same transcriptional orientation. However, unlike the teleost κ genes, genes encoding catfish σ and λ are few in number and the two isotypes are each encoded by only two clusters. Similarly, Atlantic cod λ genes are predicted to be encoded by two or three clusters. As expected, sequence and phylogenetic analyses comparisons demonstrate that catfish Vσ and Cσ genes are most similar to Vσ and Cσ genes of other ectothermic vertebrates. Although catfish and Atlantic cod Vλ genes cluster with other vertebrate Vλ genes, their Cλ sequences cluster in a distinct group separate from other vertebrate IGL C sequences. However, support for classifying these sequences as λ, is their V and J recombination signal sequence (RSS) organization. The catfish and Atlantic cod genes have typical λ-like RSS with the Vλ RSS consisting of heptamer-23 bp spacer-nonamer and the Jλ RSS consisting of heptamer-12 bp spacer-nonamer. This is the first report demonstrating the presence of Igλ in teleosts.
Regulator of complement activation (RCA) gene cluster in Xenopus tropicalisOshiumi, Hiroyuki; Suzuki, Yuzuru; Matsumoto, Misako; Seya, Tsukasa
doi: 10.1007/s00251-009-0368-9pmid: 19319518
Genome and expressed sequence tag information of Xenopus tropicalis suggested that short-consensus repeat (SCR)-containing proteins are encoded by three genes that are mapped within a 300-kb downstream of PFKFB2, which is a marker gene for the regulator of complement activation (RCA) loci in human and chicken. Based on this observation, we cloned the three cDNAs of these proteins using 3′- or 5′-RACE technique. Since their primary structures and locations of the proximity to the PFKFB2 locus, we named them amphibian RCA protein (ARC) 1, 2, and 3. Expression in human HEK293 or CHO cells suggested that ARC1 is a soluble protein of Mr ∼67 kDa, ARC2 is a membrane protein with Mr 44 kDa, and ARC3 a secretary protein with a putative transmembrane region. They were N-glycosylated during maturation. In human and chicken RCA clusters, the order in which genes for soluble, GPI-anchored, and membrane forms of SCR proteins are arranged is from the distant to proximity to the PFKFB2 gene. However, the amphibian ARC1, 2, and 3 resembled one another and did not reflect the same order found in human and chicken RCA genes. This may be due to self-duplication of ARCs to form a family, and it evolved after the amphibia separated from the ancestor of the amniotes, which possessed soluble, GPI-anchored, and membrane forms of SCR protein members. Taken together, frog possesses a RCA locus, but the constitution of the ARC proteins differs from that of the amniotes with a unique self-resemblance.
Comparative genomic analysis of the major histocompatibility complex class I region in the teleost genus OryziasMehta, Ratnesh; Nonaka, Mayumi; Nonaka, Masaru
doi: 10.1007/s00251-009-0371-1pmid: 19350233
The major histocompatibility complex (MHC) class I region of teleosts harbors a tight cluster of the class IA genes and several other genes directly involved in class I antigen presentation. Moreover, the dichotomous haplotypic lineages (termed d- and N- lineages) of the proteasome subunit beta genes, PSMB8 and PSMB10, are present in this region of the medaka, Oryzias latipes. To understand the evolution of the Oryzias MHC class I region at the nucleotide sequence level, we analyzed bacterial artificial chromosome clones covering the MHC class I region containing the d- lineage of Oryzias luzonensis and the d- and N- lineages of Oryzias dancena. Comparison among these three elucidated sequences and the published sequences of the d- and N- lineages of O. latipes indicated that the order and orientation of the encoded genes were completely conserved among these five genomic regions, except for the class IA genes, which showed species-specific variation in copy number. The PSMB8 and PSMB10 genes showed trans-species dimorphism. The remaining regions flanking the PSMB10, PSMB8, and class IA genes showed high degrees of sequence conservation at interspecies as well as intraspecies levels. Thus, the three independent evolutionary patterns under apparently distinctive selective pressures are recognized in the Oryzias MHC class I region.
Comparative genomics indicates the mammalian CD33rSiglec locus evolved by an ancient large-scale inverse duplication and suggests all Siglecs share a common ancestral regionCao, Huan; Bono, Bernard; Belov, Katherine; Wong, Emily; Trowsdale, John; Barrow, Alexander
doi: 10.1007/s00251-009-0372-0pmid: 19337729
The CD33-related sialic acid binding Ig-like lectins (CD33rSiglecs) are predominantly inhibitory receptors expressed on leukocytes. They are distinguishable from conserved Siglecs, such as Sialoadhesin and MAG, by their rapid evolution. A comparison of the CD33rSiglec gene cluster in different mammalian species showed that it can be divided into subclusters, A and B. The two subclusters, inverted in relation to each other, each encode a set of CD33rSiglec genes arranged head-to-tail. Two regions of strong correspondence provided evidence for a large-scale inverse duplication, encompassing the framework CEACAM-18 (CE18) and ATPBD3 (ATB3) genes that seeded the mammalian CD33rSiglec cluster. Phylogenetic analysis was consistent with the predicted inversion. Rodents appear to have undergone wholesale loss of CD33rSiglec genes after the inverse duplication. In contrast, CD33rSiglecs expanded in primates and many are now pseudogenes with features consistent with activating receptors. In contrast to mammals, the fish CD33rSiglecs clusters show no evidence of an inverse duplication. They display greater variation in cluster size and structure than mammals. The close arrangement of other Siglecs and CD33rSiglecs in fish is consistent with a common ancestral region for Siglecs. Expansion of mammalian CD33rSiglecs appears to have followed a large inverse duplication of a smaller primordial cluster over 180 million years ago, prior to eutherian/marsupial divergence. Inverse duplications in general could potentially have a stabilizing effect in maintaining the size and structure of large gene clusters, facilitating the rapid evolution of immune gene families.