Abstract
BackgroundCryptosporidium hominis is a dominant species for human cryptosporidiosis. Within the species, IbA10G2 is the most virulent subtype responsible for all C. hominis–associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. In this study, we sequenced the genomes of two field specimens from each of the two subtypes and conducted a comparative genomic analysis of the obtained sequences with those from the only fully sequenced Cryptosporidium parvum genome.ResultsAltogether, 8.59-9.05 Mb of Cryptosporidium sequences in 45–767 assembled contigs were obtained from the four specimens, representing 94.36-99.47% coverage of the expected genome. These genomes had complete synteny in gene organization and 96.86-97.0% and 99.72-99.83% nucleotide sequence similarities to the published genomes of C. parvum and C. hominis, respectively. Several major insertions and deletions were seen between C. hominis and C. parvum genomes, involving mostly members of multicopy gene families near telomeres. The four C. hominis genomes were highly similar to each other and divergent from the reference IaA25R3 genome in some highly polymorphic regions. Major sequence differences among the four specimens sequenced in this study were in the 5′ and 3′ ends of chromosome 6 and the gp60 region, largely the result of genetic recombination.ConclusionsThe sequence similarity among specimens of the two dominant outbreak subtypes and genetic recombination in chromosome 6, especially around the putative virulence determinant gp60 region, suggest that genetic recombination plays a potential role in the emergence of hyper-transmissible C. hominis subtypes. The high sequence conservation between C. parvum and C. hominis genomes and significant differences in copy numbers of MEDLE family secreted proteins and insulinase-like proteases indicate that telomeric gene duplications could potentially contribute to host expansion in C. parvum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1517-1) contains supplementary material, which is available to authorized users.
Highlights
Cryptosporidium hominis is a dominant species for human cryptosporidiosis
Genome coverage and bacterial contamination Among the two specimens sequenced by 454 technology, 424 of the 443 contigs generated from the IbA10G2 specimen 30974 and 767 of the 1,464 contigs from the IaA28R4 specimen 33537 mapped to the eight chromosomes of the C. parvum IOWA isolate, representing 8,816,174 and 8,590,919 bp, giving a 96.9% and 94.4% coverage of the genomes, respectively (Table 2, Additional file 1: Figure S1)
The C. parvum genome was used as the reference because it is the most complete genome fully assembled into eight chromosomes with the aid of a physical HAPPY map generated prior to the sequencing effort [27], and has ~97% sequence similarity to the reference C. hominis TU502 (IaA25R3) genome
Summary
Cryptosporidium hominis is a dominant species for human cryptosporidiosis. IbA10G2 is the most virulent subtype responsible for all C. hominis–associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. Cryptosporidium spp. inhabit the brush borders of the gastrointestinal and respiratory epithelium of various vertebrates, causing enterocolitis, diarrhea, and cholangiopathy in humans [1]. Cryptosporidiosis is one of the most important causes of moderate-to-severe diarrhea and diarrhea-associated deaths in children in developing countries [3] and a major cause for waterborne and foodborne outbreaks of human illness in industrialized nations [4,5]. It is estimated that there are approximately 750,000 annual cases of cryptosporidiosis in the United States [5]
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