Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this part of the immune system have been limited. Using a population sample of whole-genome resequencing data from wild bank voles (n = 31), we estimated the extent of genetic diversity and tested for signatures of balancing selection in multiple complement genes (n = 44). Complement genes showed higher values of standardised β (a statistic expected to be high under balancing selection) than the genome-wide average of protein coding genes. One complement gene, FCNA, a pattern recognition molecule that interacts directly with pathogens, was found to have a signature of balancing selection, as indicated by the Hudson-Kreitman-Aguadé test (HKA) test. Scans for localised signatures of balancing selection in this gene indicated that the target of balancing selection was found in exonic regions involved in ligand binding. The present study adds to the growing evidence that balancing selection may be an important evolutionary force on components of the innate immune system. The identified target in the complement system typifies the expectation that balancing selection acts on genes encoding proteins involved in direct interactions with pathogens.

中文翻译：

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野生啮齿动物补体系统的平衡选择

病原体施加的选择压力会影响宿主的遗传多样性模式。特别是在免疫系统中，许多基因编码与病原体发生拮抗相互作用的蛋白质，为共同进化铺平了道路，这种共同进化由于平衡选择而导致遗传多样性增加。补体系统是先天免疫的关键组成部分。许多补体蛋白直接与病原体相互作用，要么通过识别病原体分子激活补体，要么通过充当病原体免疫逃避机制的目标。因此，可以预期补体基因是病原体介导的平衡选择的重要目标，但对免疫系统这一部分的这种选择的分析是有限的。使用来自野生银行田鼠 (n = 31) 的全基因组重测序数据的群体样本，我们估计了遗传多样性的程度并测试了多个补体基因 (n = 44) 中平衡选择的特征。补体基因显示出比蛋白质编码基因的全基因组平均值更高的标准化 β 值（在平衡选择下预计该统计数据会很高）。一个补体基因 FCNA 是一种直接与病原体相互作用的模式识别分子，被发现具有平衡选择的特征，如 Hudson-Kreitman-Aguadé 检验 (HKA) 检验所示。扫描该基因中平衡选择的局部特征表明平衡选择的目标存在于参与配体结合的外显子区域。本研究增加了越来越多的证据，表明平衡选择可能是先天免疫系统组成部分的重要进化力量。补体系统中确定的目标代表了平衡选择作用于编码与病原体直接相互作用的蛋白质的基因的预期。