Shared epitopes among HLA class II alleles: gene conversion, common ancestry and balancing selection.
Shared epitopes among HLA class II alleles: gene conversion, common ancestry and balancing selection.
复制标题
HLA II 类等位基因之间的共享表位：基因转换、共同祖先和平衡选择。
DOI：
10.1016/0167-5699(91)90143-h
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
U. Gyllensten
中科院分区：
文献类型：
--
作者：
H. Erlich;U. Gyllensten
HLA II类序列多态性的程度和模式提出了各种各样的进化问题，特别是那些关于产生多样性的遗传机制，变化率和保持这种变化的选择压力的性质。灵长类MHC II类序列的系统发育分析表明，等位基因谱系是古老的，早在类人猿物种分离之前就已经分化。然而，对于f3链基因座，在这些谱系中，相当大的等位基因多样性发生在物种形成之后。不同等位基因含有共同序列基序的多态性的惊人拼凑模式可以解释为共同的祖先，基因转换或趋同进化，这取决于位置的共享epiterate.The起源的主要组织相容性复合体（MHC）基因座观察到的广泛的多态性一直是相当大的争议和猜测的主题1 6。负责序列变异的遗传机制以及维持多态性的选择压力仍然是MHC进化领域的开放性问题。“跨物种进化”的假说6提出，在当代物种中观察到的丰富的多态性来自祖先物种中存在的等位基因多样性，并已维持了数百万年（通过选择，或者像最初的提议一样，通过遗传漂变），几乎没有物种形成后的多样化。这一假说将多态性起源的问题推到了几百万年前，但并没有解决多态性产生的机制。尽管如此，这是一种非常有价值和有影响力的思考MHC进化的方式。在提出祖先多态性之前，普遍的观点是多态性反映了高突变率;点突变和序列交换机制被认为产生多样性，然后被选择所青睐。这个模型预测最近（即后物种形成）蚀变多样化。一般来说，这些模型不需要相互排斥;事实上，不同的解释似乎可以解释不同MHC基因座甚至同一基因座不同部分的多态性。
The extent and pattern of HLA class II sequence polymorphism raise a variety of evolutionary questions, notably those concerning the genetic mechanisms for generating diversity, the rate of change and the nature of the selection pressure maintaining this variation. Phylogenetic analysis of primate MHC class ii sequences suggests that the allelic lineages are ancient, having diverged long before separation of the hominoid species. For the f3-chain loci, however, considerable allelic diversification within these lineages has occurred after speciation. The striking patchwork pattern of polymorphism with different alleles containing common sequence motifs can be accounted for by common ancestry, by gene conversion or by convergent evolution, depending on the location of the shared epitope.The origin of the extensive polymorphism observed at the major histocompatibility complex (MHC) loci has been the subject of considerable controversy and speculation 1 6. The genetic mechanisms responsible for sequence variation as well as the selective pressures for maintaining the polymorphism remain open questions in the field of MHC evolution. The hypothesis of'trans-species evolution'6 proposes that the wealth of polymorphism observed in contemporary species is derived from the allelic diversity present in the ancestral species and has been maintained over millions of years (by selection or, as in the initial proposal, by genetic drift) with little postspeciation diversification. This hypothesis pushes the question of the origin of polymorphism back several million years, but does not address the mechanism by which it is generated. Nonetheless, it has been a very valuable and influential way of thinking about MHC evolution. Prior to the proposal of ancestral polymorphism, a common view was that the polymorphism reflected high mutation rates; point mutations and sequence exchange mechanisms were thought to generate diversity which was then favored by selection. This model predicted recent (that is post-speciation) altetic diversification. In general, these models need not be mutually exclusive; in fact, different explanations appear to account for the polymorphism at different MHC loci and even in different parts of the same locus.