Multiple targets of balancing selection in Leishmania donovani complex parasites

The Leishmania donovani species complex, comprising L. donovani and L. infantum, are the causative agents of visceral leishmaniasis, which cause 20-40,000 fatalities a year. Here, we conduct a screen for balancing selection in these species. We sequence 93 isolates of L. infantum from Brazil and used 387 publicly-available L. donovani and L. infantum genomes, to describe the global diversity of this species complex. We identify five genetically-distinct populations that are sufficiently represented by genomic data to search for signatures of selection. We show that Betascan2 and NCD2 metrics identified multiple genes with robust signatures of balancing selection. We produce a curated set of 19 genes with the most robust signatures, including zeta toxin, nodulin-like and flagellum attachment proteins. Candidates were generally not shared between populations, consistent with divergent rather than long-term balancing selection in these species. This study highlights the extent of genetic divergence between L. donovani complex parasites and provides a small list of candidate genes that appear to be subject to strong diversifying selection.

杜氏利什曼原虫物种复合体（Leishmania donovani species complex）涵盖杜氏利什曼原虫（L. donovani）与婴儿利什曼原虫（L. infantum），是内脏利什曼病的致病原，每年造成2万至4万例死亡。本研究针对该类物种开展平衡选择筛选：我们对源自巴西的93株婴儿利什曼原虫分离株进行全基因组测序，并整合387株公开可得的杜氏利什曼原虫与婴儿利什曼原虫基因组数据，以解析该物种复合体的全球遗传多样性格局。我们鉴定出5个遗传特征迥异的种群，其基因组数据覆盖度足以开展选择信号搜寻分析。研究表明，Betascan2与NCD2两种统计指标可筛选出多个携带稳健平衡选择信号的基因。我们经人工筛选整理得到19个具有最强稳健平衡选择信号的候选基因，涵盖ζ毒素（zeta toxin）、类结瘤蛋白（nodulin-like）与鞭毛附着蛋白（flagellum attachment proteins）等类型。候选基因在不同种群间普遍不存在共享现象，这与该类物种所经历的歧化选择而非长期平衡选择的特征相符。本研究阐明了杜氏利什曼原虫复合体寄生虫间的遗传分化程度，并提供了一份受强烈歧化选择的候选基因清单。