Human cryptosporidiosis is the leading protozoan cause of diarrhoeal mortality worldwide, and a preponderance of infections is caused by Cryptosporidium hominis and C. parvum. Both species consist of several subtypes with distinct geographical distributions and host preferences (that is, generalist zoonotic and specialist anthroponotic subtypes). The evolutionary processes that drive the adaptation to the human host and the population structures of Cryptosporidium remain unknown. In this study, we analyse 21 whole-genome sequences to elucidate the evolution of anthroponosis. We show that Cryptosporidium parvum splits into two subclades and that the specialist anthroponotic subtype IIc-a shares a subset of loci with C. hominis that is undergoing rapid convergent evolution driven by positive selection. C. parvum subtype IIc-a also has an elevated level of insertion and deletion mutations in the peri-telomeric genes, which is also a characteristic of other specialist subtypes. Genetic exchange between Cryptosporidium subtypes plays a prominent role throughout the evolution of the genus. Interestingly, recombinant regions are enriched for positively selected genes and potential virulence factors, which indicates adaptive introgression. Analysis of 467 gp60 sequences collected from locations across the world shows that the population genetic structure differs markedly between the main zoonotic subtype (isolation-by-distance) and the anthroponotic subtype (admixed population structure). We also show that introgression between the four anthroponotic Cryptosporidium subtypes and species included in this study has occurred recently, probably within the past millennium.
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This work was supported by funds awarded to K.M.T. and R.M.C. from the FP7-KBBE EU project AQUAVALENS, grant agreement 311846 from the European Union was awarded to P.R.H. and a Biotechnology and Biological Sciences Research Council grant (BB/N02317X/1) awarded to C.v.O., as well as support from the Earth & Life Systems Alliance. P.R.H. is supported by the National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool, in partnership with Public Health England and in collaboration with University of East Anglia, University of Oxford and the Institute of Food Research. P.R.H. is based at the University of East Anglia. The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health or Public Health England. J.A.P. and M.T.S. were supported by funding from the Knowledge Economy Skills Scholarships and received strategic funding from the Biotechnology and Biological Sciences Research Council. We thank G. Pérez-Cordón for VNTR validation of isolates.
K.M.T., R.M.C., P.R.H., J.L.N. and C.v.O. conceived the study. J.L.N. and C.v.O. designed the analyses. J.L.N., J.A.P., G.R., M.T.S., P.R.H., K.M.T. and R.M.C. were involved in the acquisition of data. J.L.N. conducted the meta-analysis. J.L.N. and C.v.O. conducted the evolutionary genetic analyses with input from T.C.M. for the phylogenetic analysis and B.J.W. for the recombinant analyses. J.L.N., T.C.M and C.v.O. drafted the submitted manuscript. All authors contributed to revising the draft, had full access to all the data and read and approved the final manuscript.
The authors declare no competing interests.
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Nader, J.L., Mathers, T.C., Ward, B.J. et al. Evolutionary genomics of anthroponosis in Cryptosporidium. Nat Microbiol 4, 826–836 (2019). https://doi.org/10.1038/s41564-019-0377-x
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