Cryptosporidium is the second leading cause of death due to diarrhoeal disease worldwide, particularly among neonatal animals, young children and the immunocompromised. Despite the global health burden, its prevalence and transmission rates remain high due to a lack of treatment options and limited tools to accurately track transmission and identify infection sources in a local context.
Human cryptosporidiosis is caused by two major species, C. hominis and C. parvum. Current studies of the molecular epidemiology, species sub-structuring and transmission dynamics of these species are largely limited to single or multi-locus genotyping. However, there is no standardised approach for these markers.
Whole genome sequencing of faecal isolates presents an alternative for population and evolutionary analysis to improve our understanding of transmission and epidemiological distribution of Cryptosporidium worldwide. We have compiled and undertaken comprehensive genomic variant, population structure and genetic analysis of all currently available (N~95) and 27 newly sequenced C. hominis isolates. We assessed global variation in the genome, divergence hotspots, demographic history and overall population structuring within and among these isolates using whole genome data and compared this to existing ‘population’ marker loci for the species.
Our analysis is the first to demonstrate substantial population structuring within C. hominis at continental and national scales. We observed varying degrees of recombination and effective population sizes across the continents, which helped us to deduce the demographic history of C. hominis. We also show that this complex structure is not reflected by currently used population markers, such as the glycoprotein gene (gp60). Hence, we identified genomic regions under evolutionary forces and discuss their potential as novel, robust population markers for multi-locus genotyping. Furthermore, we identified additional markers that had undergone diversification and adapted to local populations.