MHC DQA基因的分子进化研究——Ⅱ.基于核苷酸替换和SCU偏移的系统发育的分析

Molecular Evolution of MHC DQA Genes——Ⅱ. Phylogenetic Analysis Based on Nucleotide Substitution and SCU Bias

根据23个等位基因不同外显子(EN)的核苷酸(NT)替换及同义密码子使用谱(SCU)偏移研究了哺乳类7种动物MHC DQA座位的系谱发育关系。发现:(1)在大时间尺度内,MHC DQA基因进化速率(1.0×10^(-9),其中EN2为1.3×10^(-9)9NT/位点/年)与一般核基因相似;鼠类DQA基因的NT替换速率大致是其他哺乳类的2倍;(2)证实DQA等位基因多态性是在哺乳动物分化以后才逐渐形成的;推测牛类也存在与绵羊DQA2即OLA-DQA(c17-2)对等的具有最近共同祖先的DQA2基因座位有待发现;HLA-DQA2系谱与HLA-DQA1祖先的分化年代在20～12Mya(百万年前),HLA-DQA1各等位基因分化时间在24Mya至1Mya以内,因此产生HLA-DQA2座位的基因重组发生在HLA-DQA1产生少数几个等位基因之后;(3)基于SCU分化度的进化树从一个新的角度体现了DQA基因的系统发育关系,并显示HLA-DQA2具有特殊的SCU,提示在DQA基因的进化中产生了SCU的分化,SCU系统树在进化上有重要价值和特殊意义。改进了基因的SCU分化度和SCU相似系数的估算方法。

Phylogenetics of 23 alleles at MHC DQA loci in 7 mammalian species wasstudied based on their nucleotide (NT) substitution and synonymous codon usage (SCU)bias. (1) It was demonstrated that the NT substitution rates are 1.0×10^(-9)NT/ site /yr for exon2 and 1.3×10^(-9) NT / site / yr for exon2-4 in a large time scale, which issimilar to other nuclear genes, while for mouse and rat the rates are nearly twice ashigh as above mentioned. (2) The DQA locus diversity and their interallelic diversitydeveloped long after the radiation of mammalian 80Mya (million years ago). Thebovine counterpart, of, and with the same recent ancestor of ovine DQA2, remains tobe discovered. HLA-DQA2 locus split from HLA-DQA1 ancestor at the time between12～20 Mya while allele diversity of HLA-DQA1 emerged and developed from 24Mya to less than 1 Mya. (3)The phylogenetic trees based on SCU divergence reflectthe phylogenetics of MHC DQA genes quite well generally in a new respect andreveal that HLA-DQA2 has a distinctive SCU bias different from all other MHC DQAlocianalyzed. It indicates that SCU statistics plays an important and unique role inphylbgenetic analysis of orthologous genes. The method to estimate the SCUdivergence and SCU similarity was improved in this research.