Origin and evolution of HLA class I pseudogenes.
Origin and evolution of HLA class I pseudogenes.
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DOI：
10.1093/oxfordjournals.molbev.a040201
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发表时间：
1995-03
影响因子：
10.7
通讯作者：
Austin L. Hughes
中科院分区：
文献类型：
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作者：
Austin L. Hughes
HLA（人类主要组织相容性复合体，或MHC）区域包括三种类型的I类MHC基因：(1)Ia类位点（HLA- a， -B和-C），它们是高表达和多态的；(2) Ib类基因座，表达和多态性显著降低；(3)未表达的I类假基因。系统发育分析表明，Ib类和I类假基因都是由Ia类基因座的重复产生的。在Ia类基因中保守的5'调控元件在Ib类和I类假基因中都不保守，但前者显示出在编码区非同义位点的纯化选择，而后者缺乏这种选择。在HLA I类区域，图谱距离和系统发育距离之间几乎没有对应关系，表明存在复杂的串联基因重复历史。此外，对不同基因区域的系统发育分析表明，一些I类基因是进化链，可能是基因座间重组过程的结果。例如，HLA-92假基因的5'侧区是由与HLA-B和-C相关的基因提供的；当与HLA-B和-C相关的基因将外显子1-3（以及中间的内含子）捐献给与HLA-70假基因相关的基因时，HLA-A基因就产生了。
The HLA (human major histocompatibility complex, or MHC) region includes three types of class I MHC genes: (1) class Ia loci (HLA-A, -B, and -C), which are highly expressed and polymorphic; (2) class Ib loci, which have much reduced expression and polymorphism; and (3) unexpressed class I pseudogenes. Phylogenetic analysis suggests that both class Ib loci and class I pseudogenes arose by duplication of class Ia loci. 5' regulatory elements conserved in class Ia genes are not conserved in either class Ib or class I pseudogenes, but the former show evidence of purifying selection at nonsynonymous sites in coding regions that is lacking in the latter. In the HLA class I region, there is little correspondence between map distance and phylogenetic distance, suggesting a complex history of tandem gene duplications. Furthermore, separate phylogenetic analysis of different gene regions suggests that several class I genes are evolutionary chaemeras, which presumably have arisen as a result of a process of interlocus recombination. For example, the 5' flanking region of the HLA-92 pseudogene was donated by a gene related to HLA-B and -C; and the HLA-A gene arose when exons 1-3 (and intervening introns) were donated to a gene related to the HLA-70 pseudogene by a gene related to HLA-B and -C.