Recent origin of HLA-DRB1 alleles and implications for human evolution
Recent origin of HLA-DRB1 alleles and implications for human evolution
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DOI：
10.1038/ng0398-237
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发表时间：
1998-03-01
期刊：
影响因子：
30.8
通讯作者：
Gyllensten, U
中科院分区：
文献类型：
--
作者：
Bergström, TF;Josefsson, A;Gyllensten, U
HLA I类和II类基因座是人类基因组中最高度多态性的编码区。基于物种之间等位基因编码序列的相似性，已经声称HLA多态性是古老的，并且早于人类（Homo）和黑猩猩（Pan）的分离，4- 740万年前。然而，内含子序列的分析，提供了一个更近的起源和快速生成的等位基因在HLA II类DRB 1基因座的支持。人类的DRB 1等位基因可以分成几个组（等位基因谱系）;这些谱系中的大多数在人属和泛人种分离之前就已经彼此分化了。然而，这样一个谱系中的等位基因似乎平均有25万年的历史，这意味着当代人类135个以上的DRB 1等位基因中的绝大多数（超过90%）是在人属和泛人种分离之后产生的。等位基因谱系内等位基因的合并时间表明，早期原始人类（过去100万年）的有效人口规模（N-e）约为10（4）个个体，与基于其他核基因座和线粒体DNA的估计相似。除了一个例外，使外显子2序列多样化的遗传机制（基因转换和点突变）似乎没有延伸到相邻的内含子序列。编码β折叠的外显子2的部分与周围的内含子一起进化，而α螺旋似乎经历了类似基因转换的事件，这表明这种交换事件是高度局部化的，并且发生在极短的序列段上。
The HLA class I and class II loci are the most highly polymorphic coding regions in the human genome. Based on the similarity of the coding sequences of alleles between species, it has been claimed that the HLA polymorphism is ancient and predates the separation of human (Homo) and chimpanzee (Pan), 4-7.4 Myr ago. Analysis of intron sequences, however, provides support for a more recent origin and for rapid generation of alleles at the HLA class II DRB1 locus. The human DRB1 alleles can be divided into groups (allelic lineages); most of these lineages have diverged from each other before the separation of Homo and Pan. Alleles within such a lineage, however, appear to be, on average, 250,000 years old, implying that the vast majority (greater than 90%) of the more than 135 contemporary human DRB1 alleles have been generated after the separation of Homo and Pan. The coalescence time of alleles within allelic lineages indicates that the effective population size (N-e) for early hominids (over the last 1 Myr) was approximately 10(4) individuals, similar to estimates based on other nuclear loci and mitochondrial DNA. With a single exception, the genetic mechanisms (gene conversion and point mutation) that have diversified the exon-2 sequences do not appear to extend into the adjacent intron sequences. The part of exon 2 encoding the beta-sheet evolves in concert with the surrounding introns, while the alpha-helix appears to have been subjected to gene conversion-like events, suggesting that such exchange events are highly localised and occur over extremely short sequence tracts.