Kupfermann H, Mayer W E, O'hUigin C, Klein D, Klein J
Department of Immunogenetics, Max-Planck Institute for Biology, Tübingen, Germany.
Hum Immunol. 1992 Aug;34(4):267-78. doi: 10.1016/0198-8859(92)90026-j.
A high degree of polymorphism and high nucleotide diversity mark the functional genes of the major histocompatibility complex (Mbc). Alleles at the different Mbc loci can be classified into distinct lineages that are shared between species and, therefore, are presumed to have been founded before speciation. We have sequenced the most polymorphic part of 25 gorilla Mbc-DRB genes from six individuals. (The DRB genes code for the beta-polypeptide chain of the alpha beta heterodimer that constitutes one family of the class II MHC molecules.) Fifteen of the sequences identify new alleles at four DRB loci; each of the six gorillas was heterozygous at one of the loci at least. Thirteen of the alleles could be assigned to lineages identified previously; the remaining two alleles represent new lineages. All the major human DRB allelic lineages are now known to be shared with apes, and all must have originated before the human-gorilla-chimpanzee divergence more than six million years (my) ago. The presence of some of the gorilla and human lineages in Old World monkeys suggests that these lineages emerged before the divergence of apes and cercopithecids. We argue that the major allelic lineages at the DRB1 locus began to diverge shortly after the rounds of duplication that generated the different DRB loci now found in the hominoids and that this event occurred more than 30 my ago. Comparison of closely related gorilla DRB sequences indicates that polymorphism may be generated by several mechanisms: point mutations, slippage during DNA replication, and recombination. Deduced gene linkages provide evidence for transspecies evolution of haplotype polymorphism.
高度的多态性和高核苷酸多样性是主要组织相容性复合体（Mhc）功能基因的特征。不同Mhc位点的等位基因可分为不同的谱系，这些谱系在物种间共享，因此推测在物种形成之前就已存在。我们对来自6只个体的25个大猩猩Mhc-DRB基因的最具多态性的部分进行了测序。（DRB基因编码构成II类MHC分子一个家族的αβ异二聚体的β多肽链。）其中15个序列在4个DRB位点鉴定出了新的等位基因；6只大猩猩中的每只至少在其中一个位点是杂合的。13个等位基因可归入先前确定的谱系；其余2个等位基因代表新的谱系。现在已知所有主要的人类DRB等位基因谱系都与猿类共享，并且所有这些谱系肯定在600多万年前人类-大猩猩-黑猩猩分化之前就已起源。旧世界猴中存在一些大猩猩和人类的谱系，这表明这些谱系在猿类和猕猴科动物分化之前就已出现。我们认为，DRB1位点的主要等位基因谱系在产生现在在类人猿中发现的不同DRB位点的复制轮次之后不久就开始分化，并且这一事件发生在3000多万年前。对密切相关的大猩猩DRB序列的比较表明，多态性可能由多种机制产生：点突变、DNA复制过程中的滑动和重组。推导的基因连锁为单倍型多态性的跨物种进化提供了证据。
