Takahata N
National Institute of Genetics, Mishima, Japan.
Proc Biol Sci. 1991 Jan 22;243(1306):13-8. doi: 10.1098/rspb.1991.0003.
The extent of amino acid differences of major histocompatibility complex molecules within species is unusually high, consistent with the finding that some pairs of alleles have persisted for more than ten million years and the view that the polymorphism has been maintained by natural selection. The disparity between synonymous and non-synonymous substitutions in the antigen recognition site, however, suggests that some non-synonymous sites have undergone a number of substitutions whereas others have little or none. To describe statistically such an overdispersed underlying process, commonly used Poisson processes are inadequate. An alternative process leads to the surprising conclusion that each non-synonymous site has accumulated as many as 2.6 substitutions, on the average, in the two lineages leading to humans and mice. The standard deviation is also very large (6.6) and the dispersion index (the ratio of the variance to the mean) is at least 17. The substitution process thus inferred qualitatively agrees with the disposition (a boomerang pattern) of substitutions between HLA-A2 and Aw68 alleles, and quantitatively agrees well with that expected where the evolution of major histocompatibility complex molecules has long been driven mostly by balancing selection.
主要组织相容性复合体分子在物种内的氨基酸差异程度异常高，这与某些等位基因对已持续存在超过一千万年的发现以及多态性由自然选择维持的观点一致。然而，抗原识别位点中同义替换和非同义替换之间的差异表明，一些非同义位点经历了多次替换，而其他位点则很少或没有替换。为了从统计学上描述这种过度分散的潜在过程，常用的泊松过程并不适用。另一种过程得出了惊人的结论：在导致人类和小鼠的两个谱系中，每个非同义位点平均积累了多达2.6次替换。标准差也非常大（6.6），离散指数（方差与均值之比）至少为17。由此推断出的替换过程在定性上与HLA - A2和Aw68等位基因之间替换的分布（一种回飞镖模式）一致，在定量上与主要组织相容性复合体分子的进化长期以来主要由平衡选择驱动时预期的情况非常吻合。
