The evolutionary genomics of anthroponosis in Cryptosporidium

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Type Article
Original languageEnglish
JournalNature Microbiology
Publication statusPublished - 04 Mar 2019
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Human cryptosporidiosis is a leading protozoan cause of diarrhoeal mortality worldwide, and a preponderance of infections is caused by anthroponotic Cryptosporidium hominis and zoonotic Cryptosporidium parvum. In this study, we analyse 21 whole genome sequences (WGS) to elucidate the evolution and phylogeny of strictly human-infecting strains and generalist zoonotic strains. In addition, we conduct a meta-analysis to establish the distribution of Cryptosporidium species and subtypes globally, and describe the evolutionary changes of this pathogen during its association with its human host. Here, we show that the C. parvum forms two sister groups; an anthroponotic and zoonotic phenotype. We propose to split these into two separate subspecies; C. parvum parvum (Cpp) and C. parvum anthroponosum (Cpa) for the following reasons. Firstly, Cpa possesses a common subset of loci undergoing rapid convergent evolution driven by positive selection. Secondly, a relative excess of frameshift indels in Cpa and other strains with narrow host range is consistent with adaptation to a single species, i.e. the human host. Thirdly, the population genetic structure in Europe differs markedly between Cpp (isolation-by-distance) and Cpa (admixed population structure). Finally, we detect an elevated level of genetic introgression in the Cpa genome around potential virulence factors, and in genes under positive selection. Our analyses show that genetic introgression between subtypes and species plays a prominent role throughout the evolution of Cryptosporidium, and that the four human-infective Cryptosporidium (sub)species included in this study speciated recently, possibly within the past millennium.