Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str. 2, 24306 Plön, Germany.
Evolution. 2011 Aug;65(8):2380-90. doi: 10.1111/j.1558-5646.2011.01288.x. Epub 2011 Apr 20.
The major histocompatibility complex (MHC), coding for antigen presenting molecules of the adaptive immune system, represents one of the most polymorphic regions in the vertebrate genome. The exceptional polymorphism, which is potentially maintained by balancing selection under host-parasite coevolution, comprises excessive sequence divergence among alleles as well as ancient allelic lineages that predate species divergence (trans-species polymorphism). Here, the mechanisms that are proposed to maintain such sequence divergence and ancient lineages are investigated. Established computational antigen-binding prediction algorithms, which are based on empirical databases, are employed to determine the overlap in bound antigens among individual MHC class IIB alleles. The results show that genetically more divergent allele pairs experience less overlap and thus present a broader range of potential antigens. These findings support the divergent allele advantage hypothesis and furthermore suggest an evolutionary advantage explaining the maintenance of divergent allelic lineages, that is, trans-species polymorphism. In addressing a quantitative rather than qualitative aspect of MHC alleles, these insights highlight a new direction for future research on MHC evolution.
主要组织相容性复合体 (MHC) 编码适应性免疫系统的抗原呈递分子，是脊椎动物基因组中多态性最高的区域之一。这种特殊的多态性可能是由宿主-寄生虫共同进化下的平衡选择维持的，包括等位基因之间的过度序列分化以及早于物种分化的古老等位基因谱系（跨物种多态性）。在这里，研究了维持这种序列分化和古老谱系的机制。采用基于经验数据库的成熟计算性抗原结合预测算法，确定个体 MHC 类 IIB 等位基因之间结合抗原的重叠。结果表明，遗传上更为分化的等位基因对之间的重叠较少，因此呈现出更广泛的潜在抗原范围。这些发现支持了分化等位基因优势假说，并进一步表明了维持分化等位基因谱系（即跨物种多态性）的进化优势。这些发现强调了 MHC 进化未来研究的一个新方向，即解决 MHC 等位基因的定量而非定性方面的问题。
