Gene duplication and divergence produce divergent MHC genotypes without disassortative mating

Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leach's storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good statistical power, we consistently found random assortment of mates at MHC. Despite random mating, birds had MHC genotypes with functionally diverged alleles, averaging 13 amino acid differences in pairwise comparisons of exon 2 alleles within individuals. To test whether this high MHC diversity in individuals is driven by evolutionary divergence of the two duplicated genes, we built a phylogenetic permutation model. The model showed that genotypic diversity was strongly impacted by sequence divergence between the most common allele of each gene, with a smaller additional impact of monophyly of the two genes. Divergence of allele sequences between genes may have reduced the benefits of actively seeking MHC-dissimilar mates, in which case the evolutionary history of duplicated genes is shaping the adaptive landscape of sexual selection.

主要组织相容性复合体（major histocompatibility complex, MHC）基因在免疫防御过程中展现出杂合子优势，这一优势反过来可推动演化出偏好MHC异型交配的配偶选择策略。然而，诸多物种并未呈现出预期的MHC异型交配模式。一种可行的解释源自基因复制后的进化进程：若两个复制产生的MHC基因发生功能分化，即便在随机交配的条件下，后代也能够继承多样化的多位点基因型。我们针对白腰叉尾海燕（Oceanodroma leucorhoa）的两个表达型MHC II类B基因，采用位点特异性引物（locus-specific primers）开展高通量测序，发现外显子2（exon 2）的等位基因可划分为两个基因特异性的单系群分支。我们借助多种度量指标以及不同的外显子2序列数据子集，针对这两个功能分化的II类B基因，检验了异型交配与随机交配的发生情况。在具备充足统计效力的前提下，我们始终一致地观测到，个体在MHC位点上呈现随机的配偶选择模式。尽管交配模式为随机，但海燕个体所拥有的MHC基因型却携带功能分化的等位基因，对个体内的外显子2等位基因开展两两比较时，平均存在13个氨基酸的差异。为检验个体内这种高水平的MHC多样性是否由两个复制基因的进化分化所驱动，我们构建了系统发育置换模型（phylogenetic permutation model）。该模型结果显示，基因型多样性主要受两个基因最常见等位基因间的序列分化影响，而两个基因的单系性也会带来较小的额外影响。基因间等位基因序列的分化或许降低了主动寻求MHC异型配偶的演化收益，在此情形下，复制基因的进化历史正塑造着性选择的适应性景观。