Comparative genomics revealed adaptive admixture in Cryptosporidium hominis in Africa

Abstract

Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 (gp60) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C. hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide diversity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses; (2) local anthroponotic transmission underpins the spread of this pathogen in Africa; (3) hybridization occurs between distinct geographical lineages; and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host–parasite coevolution.

Global population genomics of two subspecies ofCryptosporidium hominisduring 500 years of evolution

“…In particular, we show that the orthologs of mucin encoding protein CHUDE2_430 and a hypothetical protein CHUDE6_5270 are consistently identified as being under positive selection (Ka/Ks > 1) in the evolution of C. hominis subspecies. These findings corroborate similar conclusions made in previous studies on C. hominis in Africa 19 , and between C. parvum parvum zoonotic vs C. parvum anthroponosum subspecies 14 . Altogether, these data strongly suggest that these genes are directly related to invasion and human-host adaptation, presenting potential targets for diagnostics to discriminate the subspecies.…”

“…In this study, we examined the evolutionary genomics of a human associated parasite, C. hominis, studying whole genome sequence data from over a hundred C. hominis isolates from 16 low-and high-income countries across five continents. We thereby expand on earlier studies that analysed the population genomics of C. hominis in Africa 19 , and population genetic studies that used selected genomic markers 25 . In particular, we examined the evolution of two main subtype populations i.e., whole genome sequences with gp60 subtype IbA10G2, versus those that did not contain this particular gp60 sequence ("not-IbA10G2").…”

“…Relatedly, a recent genomic study of C. hominis infecting children in Bangladesh indicated that the high transmission rate and likelihood of mixed infections may be driving higher recombination levels within this species 18 . Moreover, a study in Africa also highlighted evidence of geographically isolated lineages with limited population admixture, which were also likely driven by the exchange of genetic information through recombination 19 .…”

Evolutionary epidemiology of a zoonosis

“…If two or more Cryptosporidium strains infect a single host, recombination can rapidly generate evolutionary novelty. Several recent whole genome sequencing studies [9][10][11] have explored the evolutionary genetics of Cryptosporidium. For example, a study of C. hominis in children from a Bangladeshi community found high levels of genomic recombination, possibly due to the high transmission rate and likelihood of mixed infections [9].…”

“…For example, a study of C. hominis in children from a Bangladeshi community found high levels of genomic recombination, possibly due to the high transmission rate and likelihood of mixed infections [9]. Tichkule et al [10] found evidence of population admixture between distinct geographical lineages of C. hominis in Africa, showing that these lineages have been exchanging genetic information through recombination.…”