Comparative genome analysis of two Cryptosporidium parvum isolates
with different host range
, Yongsun Lee
, Paul Hunt
, Axel Martinelli
, Max Tolkoff
, Kip Bodi
Tufts Cummings School of Veterinary Medicine, Division of Infectious Diseases, North Grafton, MA 01536, USA
Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK
Centro de Malária e Outras Doenças Tropicais, UEI Biologia Molecular, Lisbon, Portugal
Tufts University, Department of Computer Sciences, Medford, MA 02155, USA
Tufts University Core Facility, Boston, MA 02111, USA
Received 15 November 2011
Received in revised form 27 March 2012
Accepted 29 March 2012
Available online 12 April 2012
Parasites of the genus Cryptosporidium infect the intestinal and gastric epithelium of different vertebrate
species. Some of the many Cryptosporidium species described to date differ with respect to host range;
whereas some species’ host range appears to be narrow, others have been isolated from taxonomically
unrelated vertebrates. To begin to investigate the genetic basis of Cryptosporidium host speciﬁcity, the
genome of a Cryptosporidium parvum isolate belonging to a sub-speciﬁc group found exclusively in
humans was sequenced and compared to the reference C. parvum genome representative of the zoonotic
group. Over 12,000 single-nucleotide polymorphisms (SNPs), or 1.4 SNP per kilobase, were identiﬁed. The
genome distribution of SNPs was highly heterogeneous, but non-synonymous and silent SNPs were sim-
ilarly distributed. On many chromosomes, the most highly divergent regions were located near the ends.
Genes in the most diverged regions were almost twice as large as the genome-wide average. Transport-
ers, and ABC transporters in particular, were over-represented among these genes, as were proteins with
predicted signal peptide. Possibly reﬂecting the presence of regulatory sequences, the distribution of
intergenic SNPs differed according to the function of the downstream open reading frame. A 3-way com-
parison of the newly sequenced anthroponotic C. parvum, the reference zoonotic C. parvum and the
human parasite Cryptosporidium hominis identiﬁed genetic loci where the anthroponotic C. parvum
sequence is more similar to C. hominis than to the zoonotic C. parvum reference. Because C. hominis
and anthroponotic C. parvum share a similar host range, this unexpected observation suggests that pro-
teins encoded by these genes may inﬂuence the host range.
Ó 2012 Elsevier B.V. All rights reserved.
Apicomplexan parasites of the genus Cryptosporidium multiply
in the epithelium of the intestinal tract and are transmitted by
the dispersal of oocysts in the environment and particularly in
water. Many Cryptosporidium species are thought to have a narrow
host range. This is reﬂected in the name of several species, such as
Cryptosporidium canis (Fayer et al., 2001), Cryptosporidium felis or
Cryptosporidium hominis (Morgan-Ryan et al., 2002). In contrast,
other species appear to lack host speciﬁcity as they are naturally
found in a wide range of host species or can be transmitted
experimentally among taxonomically unrelated host species.
Notable examples in the latter category are Cryptosporidium par-
vum, a zoonotic parasite of humans and livestock, Cryptosporidium
meleagridis, which infects mammals and birds (Akiyoshi et al.,
2003) and the newly described species Cryptosporidium ubiquitum
(Fayer et al., 2010). In contrast to our expanding knowledge of the
complexity of the genus Cryptosporidium, little progress has been
made in identifying genetic loci controlling phenotypic traits
(Okhuysen and Chappell, 2002). The advent of methods to rapidly
re-sequence entire genomes may offer an alternative approach to
the identiﬁcation of genes controlling phenotypes in these para-
sites. This approach is enabled by the availability of the complete
sequence of a C. parvum reference isolate (Abrahamsen et al.,
2004), the partially complete sequence of the C. hominis genome
(Xu et al., 2004) and the more recently sequenced Cryptosporidium
Because C. parvum and C. hominis do not appear to recombine in
nature, genome-wide association studies to ﬁnd genetic determi-
nants of host range are not feasible. A major polymorphic trait in
C. parvum is host range. It has been known for some time that
1567-1348/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
Abbreviations: SNP, single-nucleotide polymorphism;kb, kilobase; nt,nucleotide.
Corresponding author. Address: 200 Westboro Road, North Grafton, MA 01536,
USA. Tel.: +1 508 839 79 44; fax: +1 508 839 79 11.
E-mail address: email@example.com (G. Widmer).
Present address: University of Edinburgh, Edinburgh, UK.
Present address: UCLA, Department of Biostatistics, Los Angeles, CA 90024, USA.
Infection, Genetics and Evolution 12 (2012) 1213–1221
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