Unit of Human Evolutionary Genetics.
Hum Mol Genet. 2013 Dec 1;22(23):4829-40. doi: 10.1093/hmg/ddt335. Epub 2013 Jul 12.
The study of the genetic and selective landscape of immunity genes across primates can provide insight into the existing differences in susceptibility to infection observed between human and non-human primates. Here, we explored how selection has driven the evolution of a key family of innate immunity receptors, the Toll-like receptors (TLRs), in African great ape species. We sequenced the 10 TLRs in various populations of chimpanzees and gorillas, and analysed these data jointly with a human data set. We found that purifying selection has been more pervasive in great apes than in humans. Furthermore, in chimpanzees and gorillas, purifying selection has targeted TLRs irrespectively of whether they are endosomal or cell surface, in contrast to humans where strong selective constraints are restricted to endosomal TLRs. These observations suggest important differences in the relative importance of TLR-mediated pathogen sensing, such as that of recognition of flagellated bacteria by TLR5, between humans and great apes. Lastly, we used a population genetics-phylogenetics method that jointly analyses polymorphism and divergence data to detect fine-scale variation in selection pressures at specific codons within TLR genes. We identified different codons at different TLRs as being under positive selection in each species, highlighting that functional variation at these genes has conferred a selective advantage in immunity to infection to specific primate species. Overall, this study showed that the degree of selection driving the evolution of TLRs has largely differed between human and non-human primates, increasing our knowledge on their respective biological contribution to host defence in the natural setting.
研究灵长类动物的免疫基因遗传和选择景观，可以深入了解人类和非人类灵长类动物在易感性方面存在的差异。在这里，我们探讨了选择如何驱动非洲大猿物种中一类重要的先天免疫受体—— Toll 样受体（TLR）的进化。我们对各种黑猩猩和大猩猩种群中的 10 个 TLR 进行了测序，并与人类数据集联合分析了这些数据。我们发现，与人类相比，净化选择在大猿中更为普遍。此外，在黑猩猩和大猩猩中，无论 TLR 是内体还是细胞表面，净化选择都针对 TLR，而人类中，强烈的选择限制仅限于内体 TLR。这些观察结果表明，在 TLR 介导的病原体感应方面，人类和大猿之间存在重要差异，例如 TLR5 对鞭毛菌的识别。最后，我们使用一种群体遗传学-系统发生学方法，该方法联合分析多态性和分歧数据，以检测 TLR 基因内特定密码子处选择压力的精细变化。我们发现，每个物种的不同 TLR 上的不同密码子受到正选择，这突出表明这些基因的功能变异在感染免疫方面赋予了特定灵长类物种选择性优势。总的来说，这项研究表明，TLR 进化的选择程度在人类和非人类灵长类动物之间存在很大差异，增加了我们对它们在自然环境中对宿主防御的各自生物学贡献的了解。
