Sympatric Recombination in Zoonotic Cryptosporidium Leads to Emergence of Populations with Modified Host Preference

Abstract

Genetic recombination plays a critical role in the emergence of pathogens with phenotypes such as drug resistance, virulence, and host adaptation. Here, we tested the hypothesis that recombination between sympatric ancestral populations leads to the emergence of divergent variants of the zoonotic parasite Cryptosporidium parvum with modified host ranges. Comparative genomic analyses of 101 isolates have identified seven subpopulations isolated by distance. They appear to be descendants of two ancestral populations, IIa in northwestern Europe and IId from southwestern Asia. Sympatric recombination in areas with both ancestral subtypes and subsequent selective sweeps have led to the emergence of new subpopulations with mosaic genomes and modified host preference. Subtelomeric genes could be involved in the adaptive selection of subpopulations, while copy number variations of genes encoding invasion-associated proteins are potentially associated with modified host ranges. These observations reveal ancestral origins of zoonotic C. parvum and suggest that pathogen import through modern animal farming might promote the emergence of divergent subpopulations of C. parvum with modified host preference.

Comparative genomics reveals the emergence of an outbreak-associatedCryptosporidium parvumpopulation in Europe and its spread to the USA

“…The large-scale topology was consistent with the orthologous genes-based phylogeny. Corroborating indications from previous studies (Corsi et al 2023; T. Wang et al 2022), we observed that the host species and gp60 subtypes were “scattered” along the tree, the latter indicative of limited predictive power for the deep phyletic relationships within C. parvum . However, a partial correlation with the geographical origin was found, as isolates sampled from the same region/country, from a single farm, or collected within a narrow temporal window, formed evident subclusters (e.g., all but one of the Finnish isolates formed a monophyletic clade).…”

“…Table S1 lists the information available for the 195 C. parvum isolates from humans and ruminants included in this study. The dataset comprised 123 isolates sequenced in the present study, 71 isolates from previous studies (Hadfield et al 2015; Troell et al 2016; Feng et al 2017; Corsi et al 2023; T. Wang et al 2022), and the recently assembled IOWA-ATCC genome (Baptista et al 2022), which was used as a reference genome.…”

“…Another work analysed 101 WGSs and hypothesised the existence of two ancestral populations, represented by IId isolates from China and IIa isolates from Europe. The authors proposed that the IId and IIa populations recently became sympatric in Europe, and generated hybrid genomes through recombination, possibly influencing biological traits such as host preference (T. Wang et al 2022).…”

“…Recent studies based on whole genome sequence (WGS) comparisons have started to explore the evolutionary genetics of C. parvum (Corsi et al 2023; T. Wang et al 2022; Feng et al 2017). In the work of Corsi et al (2023), analysis of 32 WGSs indicated a clear separation between European and non-European (Egypt and China) isolates, and highlighted the occurrence of recombination events between these populations.…”

“…In this study, we generated WGSs for 123 human-or ruminant-derived C. parvum isolates collected across Europe, and retrieved publicly available WGS data of 71 isolates from Europe, Egypt, China and the USA (Corsi et al 2023; T. Wang et al 2022; Feng et al 2017; Hadfield et al 2015; Troell et al 2016). Based on the largest comparative study to date, our main aim was to understand the evolution of this important zoonotic pathogen in Europe and in the USA.…”