Department of Biology, Lund University, Lund, Sweden.
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
Mol Ecol. 2020 Jun;29(11):1990-2003. doi: 10.1111/mec.15459. Epub 2020 Jun 3.
Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.
病原体介导的平衡选择通常被认为在维持遗传多样性方面发挥着重要作用，尤其是在免疫基因方面。然而，哪些免疫基因是这种选择的目标的因素在很大程度上是未知的。为了解决这个问题，我们在这里集中研究模式识别受体（PRR）信号通路，它在先天免疫中起着关键作用。我们使用来自一群 bank voles（Myodes glareolus）的全基因组重测序数据，测试了 123 个 PRR 信号通路基因中平衡选择、多效性和基因功能之间的关联。为了研究基因功能的影响，我们比较了编码（a）微生物配体受体与下游信号蛋白，以及（b）识别微生物细胞壁、鞭毛和衣壳成分的受体与识别微生物核酸特征的受体的基因。基于全编码序列的核苷酸多样性的分析表明，平衡选择主要针对多效性程度较低的受体基因。此外，编码识别微生物细胞壁等成分的受体的基因是平衡选择的更重要目标，而不是识别核酸的受体。在编码和非编码序列中对平衡选择局部特征的测试表明，这些特征主要位于内含子中，并且在 PRR 途径基因的不同功能类别中分布更加均匀。平衡选择在全编码序列中的特征主要发生在受体基因中，特别是那些编码识别微生物细胞壁等成分的受体的基因的发现，与宿主和病原体之间的共同进化是免疫基因上平衡选择的重要原因的观点一致。
