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.

中文翻译：

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比较基因组学揭示非洲人隐孢子虫的适应性混合


隐孢子虫病是非洲儿童腹泻病的主要原因，与儿童死亡率、营养不良、认知发育和生长迟缓有关。人型隐孢子虫是非洲的主要病原体，糖蛋白 60 ( gp60 ) 基因的基因分型揭示了非洲大陆不同亚型的复杂分布。然而，基于全基因组数据对亚种群结构和进化的全面探索仍有待进行。在这里，我们对 26 C的基因组进行了测序和分析。人分离株，代表不同的gp60亚型，收集于加蓬、加纳、马达加斯加和坦桑尼亚的农村地区。基于单核苷酸多态性的系统发育和聚类分析表明，分离株主要按原产国聚类，无论其gp60亚型如何。我们发现了显着的距离隔离特征，显示了本地传播的重要性，但我们也发现了不同地理区域的分离株之间杂交的证据。我们鉴定了 37 个具有极高核苷酸多样性的离群基因，并且该组编码胞外蛋白和信号肽的基因显着富集。此外，这些基因在重组区域中的发现频率比预期的要高，并且它们显示出正选择或平衡选择的独特特征。我们的结论是：（1） C.的集合种群结构。 人类只能通过全基因组分析才能准确捕获； (2) 当地人为传播是该病原体在非洲传播的基础； (3)不同地理谱系之间发生杂交； (4)基因渗入为参与宿主-寄生虫协同进化的基因的正选择或平衡选择提供了新的底物。