Meyer-Lucht Y, Sommer S
Department Animal Ecology & Conservation, Biozentrum Grindel, University of Hamburg, Martin-Luther-King-Platz 3, D - 20146 Hamburg, Germany.
Mol Ecol. 2005 Jun;14(7):2233-43. doi: 10.1111/j.1365-294X.2005.02557.x.
In vertebrates, the genes of the major histocompatibility complex (MHC) are among the most debated candidates accounting for co-evolutionary processes of host-parasite interaction at the molecular level. The exceptionally high allelic polymorphism found in MHC loci is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or rare allele advantage (= frequency dependent selection). While investigations under natural conditions are still very rare, studies on humans or mice under laboratory conditions revealed support for both hypotheses. We investigated nematode burden and allelic diversity of a functional important MHC class II gene (DRB exon2) in free-ranging yellow-necked mice (Apodemus flavicollis). Twenty-seven distinct Apfl-DRB alleles were detected in 146 individuals with high levels of amino acid sequence divergence, especially at the antigen binding sites (ABS), indicating selection processes acting on this locus. Heterozygosity had no influence on the infection status (being infected or not), the number of different nematode infections (NNI) or the intensity of infection, measured as the individual faecal egg count (FEC). However, significant associations of specific Apfl-DRB alleles to both nematode susceptibility and resistance were found, for all nematodes as well as in separate analyses of the two most common nematodes. Apodemus flavicollis individuals carrying the alleles Apfl-DRB5 or Apfl-DRB15 revealed significantly higher FEC than individuals with other alleles. In contrast, the allele Apfl-DRB*23 showed a significant association to low FEC of the most common nematode. Thus, our results provide evidence for pathogen-driven selection acting through rare allele advantage under natural conditions.
在脊椎动物中，主要组织相容性复合体（MHC）的基因是分子水平上宿主 - 寄生虫相互作用共同进化过程中最具争议的候选基因之一。MHC基因座中发现的异常高的等位基因多态性被认为是由病原体驱动的选择所维持的，这种选择通过杂合优势或稀有等位基因优势（=频率依赖性选择）介导。虽然在自然条件下的研究仍然非常罕见，但在实验室条件下对人类或小鼠的研究为这两种假设都提供了支持。我们调查了自由放养的黄颈鼠（Apodemus flavicollis）中一个功能重要的MHC II类基因（DRB外显子2）的线虫负荷和等位基因多样性。在146个个体中检测到27个不同的Apfl - DRB等位基因，氨基酸序列差异水平较高，尤其是在抗原结合位点（ABS），表明该基因座受到选择作用。杂合性对感染状态（是否感染）、不同线虫感染的数量（NNI）或感染强度（以个体粪便虫卵计数（FEC）衡量）没有影响。然而，发现特定的Apfl - DRB等位基因与线虫易感性和抗性都有显著关联，包括所有线虫以及对两种最常见线虫的单独分析。携带等位基因Apfl - DRB5或Apfl - DRB15的黄颈鼠个体的FEC显著高于携带其他等位基因的个体。相比之下，等位基因Apfl - DRB*23与最常见线虫的低FEC有显著关联。因此，我们的结果为自然条件下通过稀有等位基因优势起作用的病原体驱动选择提供了证据。
