Title: Evolutionary genomics of anthroponosis in Cryptosporidium

54 Human is the protozoan cause of diarrhoeal worldwide, and a preponderance of is caused Cryptosporidium hominis and C. parvum . 56 Both species consist of several subtypes with distinct geographic distributions and host 57 preferences (i.e. generalist zoonotic and specialist anthroponotic subtypes). The evolutionary 58 processes driving the adaptation to human host, and the population structure remain 59 unknown. In this study, we analyse 21 whole genome sequences to elucidate the evolution of 60 anthroponosis. We show that C. parvum splits into two subclades, and that the specialist 61 anthroponotic subtype IIc-a shares a subset of loci with C. hominis that are undergoing rapid 62 convergent evolution driven by positive selection. Subtype IIc-a also has an elevated level of 63 insertion-deletion (indel) mutations in the peri-telomeric genes, which is characteristic also 64 for other specialist subtypes. Genetic exchange between subtypes plays a prominent role 65 throughout the evolution of Cryptosporidium . Interestingly, recombinant regions are enriched 66 for positively selected genes and potential virulence factors, which indicates adaptive 67 introgression. Analysis of 467 gp60 sequences collected across the world shows that the 68 population genetic structure differs markedly between the main zoonotic subtype (isolation- 69 by-distance) and the anthroponotic subtype (admixed population structure). Finally, we show 70 that introgression between the four anthroponotic Cryptosporidium subtypes and species 71 included in this study has occurred recently, probably within the past millennium.