{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:36:16Z","timestamp":1791909376388,"version":"4.3.4"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cryptosporidiosis is a major global health problem and a primary cause of diarrhea, particularly in young children in low- and middle-income countries (LMICs). The zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis cause most human infections. Here, we present a comprehensive whole-genome study of C. hominis, comprising 114 isolates from 16 countries within five continents. We detect two lineages with distinct biology and demography, which diverged circa 500 years ago. We consider these lineages two subspecies and propose the names C. hominis hominis and C. hominis aquapotentis (gp60 subtype IbA10G2). In our study, C. h. hominis is almost exclusively represented by isolates from LMICs in Africa and Asia and appears to have undergone recent population contraction. In contrast, C. h. aquapotentis was found in high-income countries, mainly in Europe, North America, and Oceania, and appears to be expanding. Notably, C. h. aquapotentis is associated with high rates of direct human-to-human transmission, which may explain its success in countries with well-developed environmental sanitation infrastructure. Intriguingly, we detected genomic regions of introgression following secondary contact between the subspecies. This resulted in high diversity and divergence in genomic islands of putative virulence genes, including muc5 (CHUDEA2_430) and a hypothetical protein (CHUDEA6_5270). This diversity is maintained by balancing selection, suggesting a co-evolutionary arms race with the host. Finally, we find that recent gene flow from C. h. aquapotentis to C. h. hominis, likely associated with increased human migration, maybe driving the evolution of more virulent C. hominis variants.<\/jats:p>","DOI":"10.1093\/molbev\/msac056","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T08:07:59Z","timestamp":1647418079000},"source":"Crossref","is-referenced-by-count":29,"title":["Global Population Genomics of Two Subspecies of\n                    <i>Cryptosporidium hominis<\/i>\n                    during 500 Years of Evolution"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2940-9961","authenticated-orcid":false,"given":"Swapnil","family":"Tichkule","sequence":"first","affiliation":[{"name":"Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone M.","family":"Cacci\u00f2","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Robinson","sequence":"additional","affiliation":[{"name":"Cryptosporidium Reference Unit, Public Health Wales Microbiology and Health Protection, Singleton Hospital, Swansea, UK"},{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Chalmers","sequence":"additional","affiliation":[{"name":"Cryptosporidium Reference Unit, Public Health Wales Microbiology and Health Protection, Singleton Hospital, Swansea, UK"},{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Mueller","sequence":"additional","affiliation":[{"name":"Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2984-0620","authenticated-orcid":false,"given":"Samantha J.","family":"Emery-Corbin","sequence":"additional","affiliation":[{"name":"Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eibach","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine Hamburg, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-8158","authenticated-orcid":false,"given":"Kevin M.","family":"Tyler","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK"},{"name":"Center of Excellence for Bionanoscience Research, King Abdul Aziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5653-738X","authenticated-orcid":false,"given":"Cock","family":"van Oosterhout","sequence":"additional","affiliation":[{"name":"School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron R.","family":"Jex","sequence":"additional","affiliation":[{"name":"Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia"},{"name":"Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"2022041313284950400_msac056-B1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1126\/science.1094786","article-title":"Complete genome sequence of the apicomplexan, Cryptosporidium parvum","volume":"304","author":"Abrahamsen","year":"2004","journal-title":"Science"},{"key":"2022041313284950400_msac056-B2","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/bioinformatics\/btu005","article-title":"estMOI: estimating multiplicity of infection using parasite deep sequencing data","volume":"30","author":"Assefa","year":"2014","journal-title":"Bioinformatics"},{"key":"2022041313284950400_msac056-B3","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2022041313284950400_msac056-B4","first-page":"012401","article-title":"DensiTree 2: seeing trees through the forest","author":"Bouckaert","year":"2014","journal-title":"bioRxiv"},{"key":"2022041313284950400_msac056-B5","doi-asserted-by":"crossref","first-page":"e1003537","DOI":"10.1371\/journal.pcbi.1003537","article-title":"BEAST 2: a software platform for Bayesian evolutionary analysis","volume":"10","author":"Bouckaert","year":"2014","journal-title":"PLoS Comput Biol."},{"key":"2022041313284950400_msac056-B6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/CMR.00076-12","article-title":"Cryptosporidium pathogenicity and virulence","volume":"26","author":"Bouzid","year":"2013","journal-title":"Clin Microbiol Rev."},{"key":"2022041313284950400_msac056-B7","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cmi.2016.04.021","article-title":"Human cryptosporidiosis in Europe","volume":"22","author":"Cacci\u00f2","year":"2016","journal-title":"Clin Microbiol Infect."},{"key":"2022041313284950400_msac056-B8","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.3201\/eid1410.071273","article-title":"Cryptosporidium species and subtypes and clinical manifestations in children, Peru","volume":"14","author":"Cama","year":"2008","journal-title":"Emerg Infect Dis."},{"key":"2022041313284950400_msac056-B9","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1096\/fj.201901898RR","article-title":"Presence and structure-activity relationship of intrinsically disordered regions across mucins","volume":"34","author":"Carmicheal","year":"2020","journal-title":"FASEB J."},{"key":"2022041313284950400_msac056-B10","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1128\/IAI.68.9.5167-5175.2000","article-title":"Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody","volume":"68","author":"Cevallos","year":"2000","journal-title":"Infect Immun."},{"key":"2022041313284950400_msac056-B11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13071-019-3354-6","article-title":"Analysis of the Cryptosporidium spp. and gp60 subtypes linked to human outbreaks of cryptosporidiosis in England and Wales, 2009 to 2017","volume":"12","author":"Chalmers","year":"2019","journal-title":"Parasit Vectors"},{"key":"2022041313284950400_msac056-B12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2166\/wh.2009.185","article-title":"Detection of Cryptosporidium species and sources of contamination with Cryptosporidium hominis during a waterborne outbreak in north west Wales","volume":"8","author":"Chalmers","year":"2010","journal-title":"J Water Health"},{"key":"2022041313284950400_msac056-B13","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1128\/EC.00288-09","article-title":"Evidence for mucin-like glycoproteins that tether sporozoites of Cryptosporidium parvum to the inner surface of the oocyst wall","volume":"9","author":"Chatterjee","year":"2010","journal-title":"Eukaryot Cell"},{"key":"2022041313284950400_msac056-B14","article-title":"Evolutionary epidemiology of a zoonosis","author":"Corsi","year":"2021","journal-title":"bioRxiv"},{"key":"2022041313284950400_msac056-B15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/j.1551-8833.1998.tb08500.x","article-title":"Waterborne outbreaks of cryptosporidiosis","volume":"90","author":"Craun","year":"1998","journal-title":"J AWWA"},{"key":"2022041313284950400_msac056-B16","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"2022041313284950400_msac056-B17","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/molbev\/msi103","article-title":"Bayesian coalescent inference of past population dynamics from molecular sequences","volume":"22","author":"Drummond","year":"2005","journal-title":"Mol Biol 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