The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

中文翻译：

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天然小鼠群体中自身免疫敏感性等位基因的流行和进化起源。

SLAM / CD2基因簇中遗传多样性的进化起源，涉及小鼠自身免疫性狼疮易感性，是通过对来自全球小鼠群体的48只野生小鼠样品中来自该簇六种成员的外显子进行序列分析而研究的。在所分析的六个基因中总共鉴定出80个编码区SNP，表明该基因簇在天然小鼠种群中高度多态。这些等位基因序列的系统进化分析显示，来自多个Mus物种和亚种的等位基因聚类，表明在物种形成之前，祖先Mus种群中存在多个SLAM / CD2基因座的等位基因，并且作为多态性已经存在了超过一百万年。使用可能性密码子替换模型的非同义/同义比率的分析确定了Cd229，Cd48和Cd84中的几个片段受到正多样化选择压力的影响。这些发现支持这样的解释，即有利于功能性多态性的产生和保留的选择在倾向于自身免疫的遗传多态性的进化起源中发挥了作用。