Mammalian evolution has been influenced by viruses for millions of years, leaving signatures of adaptive evolution within genes encoding for viral interacting proteins. Synaptogyrin-2 (SYNGR2) is a transmembrane protein implicated in promoting bacterial and viral infections. A genome-wide association study of pigs experimentally infected with porcine circovirus type 2b (PCV2b) uncovered a missense mutation (SYNGR2 p.Arg63Cys) associated with viral load. In this study, CRISPR/Cas9-mediated gene editing of the porcine kidney 15 (PK15, wtSYNGR2+p.63Arg) cell line generated clones homozygous for the favorable SYNGR2 p.63Cys allele (emSYNGR2+p.63Cys). Infection of edited clones resulted in decreased PCV2 replication compared to wildtype PK15 (P<0.05), with consistent effects across genetically distinct PCV2b and PCV2d isolates. Sequence analyses of wild and domestic pigs (n>700) revealed the favorable SYNGR2 p.63Cys allele is unique to domestic pigs and more predominant in European than Asian breeds. A haplotype defined by the SYNGR2 p.63Cys allele was likely derived from an ancestral haplotype nearly fixed within European (0.977) but absent from Asian wild boar. We hypothesize that the SYNGR2 p.63Cys allele arose post-domestication in ancestral European swine. Decreased genetic diversity in homozygotes for the SYNGR2 p.63Cys allele compared to SYNGR2 p.63Arg, corroborates a rapid increase in frequency of SYGNR2 p.63Cys via positive selection. Signatures of adaptive evolution across mammalian species were also identified within SYNGR2 intraluminal loop domains, coinciding with the location of SYNGR2 p.Arg63Cys. Therefore, SYNGR2 may reflect a novel component of the host-virus evolutionary arms race across mammals with SYNGR2 p.Arg63Cys representing a species-specific example of putative adaptive evolution.

中文翻译：

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宿主 Synaptogyrin-2 在猪圆环病毒 2 型易感性中的功能和进化分析。

数百万年来，哺乳动物的进化一直受到病毒的影响，在编码病毒相互作用蛋白的基因中留下了适应性进化的特征。Synaptogyrin-2 (SYNGR2) 是一种跨膜蛋白，与促进细菌和病毒感染有关。对实验感染 2b 型猪圆环病毒 (PCV2b) 的猪进行的全基因组关联研究发现了与病毒载量相关的错义突变 (SYNGR2 p.Arg63Cys)。在这项研究中，对猪肾 15（PK15，wtSYNGR2+p.63Arg）细胞系进行 CRISPR/Cas9 介导的基因编辑，生成了与有利的 SYNGR2 p.63Cys 等位基因（emSYNGR2+p.63Cys）纯合的克隆。与野生型 PK15 相比，编辑克隆的感染导致 PCV2 复制减少 (P<0.05)，并且在遗传上不同的 PCV2b 和 PCV2d 分离株中具有一致的效果。对野猪和家猪 (n>700) 的序列分析表明，有利的 SYNGR2 p.63Cys 等位基因是家猪所独有的，并且在欧洲品种中比在亚洲品种中更占主导地位。由 SYNGR2 p.63Cys 等位基因定义的单倍型可能源自欧洲野猪中几乎固定的祖先单倍型 (0.977)，但在亚洲野猪中不存在。我们假设 SYNGR2 p.63Cys 等位基因是在欧洲祖先猪驯化后出现的。与 SYNGR2 p.63Arg 相比，SYNGR2 p.63Cys 等位基因纯合子的遗传多样性降低，证实了 SYGNR2 p.63Cys 频率通过正选择快速增加。哺乳动物物种的适应性进化特征也在 SYNGR2 腔内环域内被识别，与 SYNGR2 p.Arg63Cys 的位置一致。因此，SYNGR2可能反映了哺乳动物之间宿主病毒进化军备竞赛的一个新组成部分，SYNGR2 p.Arg63Cys代表了假定的适应性进化的物种特异性例子。