Grossen Christine, Keller Lukas, Biebach Iris, Croll Daniel
Institute of Evolutionary Biology and Environmental Studies, University of Zürich, Zürich, Switzerland; Department of Zoology, University of British Columbia, Vancouver, Canada.
Institute of Evolutionary Biology and Environmental Studies, University of Zürich, Zürich, Switzerland.
PLoS Genet. 2014 Jun 19;10(6):e1004438. doi: 10.1371/journal.pgen.1004438. eCollection 2014 Jun.
The major histocompatibility complex (MHC) is a crucial component of the vertebrate immune system and shows extremely high levels of genetic polymorphism. The extraordinary genetic variation is thought to be ancient polymorphisms maintained by balancing selection. However, introgression from related species was recently proposed as an additional mechanism. Here we provide evidence for introgression at the MHC in Alpine ibex (Capra ibex ibex). At a usually very polymorphic MHC exon involved in pathogen recognition (DRB exon 2), Alpine ibex carried only two alleles. We found that one of these DRB alleles is identical to a DRB allele of domestic goats (Capra aegagrus hircus). We sequenced 2489 bp of the coding and non-coding regions of the DRB gene and found that Alpine ibex homozygous for the goat-type DRB exon 2 allele showed nearly identical sequences (99.8%) to a breed of domestic goats. Using Sanger and RAD sequencing, microsatellite and SNP chip data, we show that the chromosomal region containing the goat-type DRB allele has a signature of recent introgression in Alpine ibex. A region of approximately 750 kb including the DRB locus showed high rates of heterozygosity in individuals carrying one copy of the goat-type DRB allele. These individuals shared SNP alleles both with domestic goats and other Alpine ibex. In a survey of four Alpine ibex populations, we found that the region surrounding the DRB allele shows strong linkage disequilibria, strong sequence clustering and low diversity among haplotypes carrying the goat-type allele. Introgression at the MHC is likely adaptive and introgression critically increased MHC DRB diversity in the genetically impoverished Alpine ibex. Our finding contradicts the long-standing view that genetic variability at the MHC is solely a consequence of ancient trans-species polymorphism. Introgression is likely an underappreciated source of genetic diversity at the MHC and other loci under balancing selection.
主要组织相容性复合体（MHC）是脊椎动物免疫系统的关键组成部分，具有极高的遗传多态性。这种非凡的遗传变异被认为是通过平衡选择维持的古老多态性。然而，最近有人提出，来自相关物种的基因渗入是另一种机制。在这里，我们提供了阿尔卑斯野生山羊（Capra ibex ibex）MHC发生基因渗入的证据。在一个通常高度多态的参与病原体识别的MHC外显子（DRB外显子2）上，阿尔卑斯野生山羊仅携带两个等位基因。我们发现其中一个DRB等位基因与家山羊（Capra aegagrus hircus）的一个DRB等位基因相同。我们对DRB基因的编码区和非编码区的2489 bp进行了测序，发现携带山羊型DRB外显子2等位基因的纯合阿尔卑斯野生山羊与一种家山羊品种的序列几乎相同（99.8%）。使用桑格测序和RAD测序、微卫星和SNP芯片数据，我们表明，包含山羊型DRB等位基因的染色体区域在阿尔卑斯野生山羊中具有近期基因渗入的特征。一个包括DRB基因座在内的约750 kb区域在携带一份山羊型DRB等位基因的个体中显示出高杂合率。这些个体与家山羊和其他阿尔卑斯野生山羊共享SNP等位基因。在对四个阿尔卑斯野生山羊种群的调查中，我们发现DRB等位基因周围的区域显示出强烈的连锁不平衡、强烈的序列聚类以及携带山羊型等位基因的单倍型之间的低多样性。MHC的基因渗入可能具有适应性，并且基因渗入显著增加了遗传上贫乏的阿尔卑斯野生山羊的MHC DRB多样性。我们的发现与长期以来的观点相矛盾，即MHC的遗传变异性仅仅是古老的跨物种多态性的结果。基因渗入可能是MHC和其他处于平衡选择下的基因座遗传多样性的一个未被充分认识的来源。
