Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA
Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA
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DOI：
10.1002/humu.20378
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发表时间：
2006-11-01
期刊：
影响因子：
3.9
通讯作者：
Wallace, Douglas C.
中科院分区：
文献类型：
--
作者：
Ruiz-Pesini, Eduardo;Wallace, Douglas C.
为了鉴定假定的适应性人类线粒体DNA（mtDNA）、转运RNA（tRNA）和核糖体RNA（rRNA）变体，我们从2，460个人类mtDNA编码序列中组装了一个连续突变树，从而提供了所有mtDNA序列变体的相对年龄。有害突变影响进化上保守的核苷酸，并且已经通过纯化选择从树的较老的内部分支中消除，而有益突变也改变保守的核苷酸，但是已经通过适应性选择在树的内部分支中富集。中性多态性改变保守性差的核苷酸，并分布在整个树。茎核苷酸比环核苷酸更受限制。通过与所有已知致病性tRNA突变的平均进化保守指数（CI）进行比较来评估这两种类型的核苷酸变体的功能重要性，从而允许区分内部分支中性和适应性tRNA变体。这表明，19%的茎和13%的环内部分支tRNA变体是潜在的适应性。由于已知的致病性rRNA突变很少，适应性rRNA变异的证据通过内支与外支中更高的茎环变体比率和升高的CI来揭示。此外，茎非典型并置碱基之间的变体主要产生新的沃森-克里克（WC）碱基对，因此也表明适应性选择。在假定的适应性tRNA和rRNA多态性中，发现一些发生在树的分支的基部，多次复发，并与改变的人类表型相关。因此，很大一部分古老的tRNA和rRNA多态性似乎是适应性的，这些都影响着今天的人类健康。穆拉特27（11），1072-1081，2006年。2006年出版Wiley-Liss，Inc.
In order to identify putative adaptive human mitochondrial DNA (mtDNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) variants, we assembled a sequential mutational tree from 2,460 human mtDNA coding sequences, thus providing the relative age of all mtDNA sequence variants. Deleterious mutations affect evolutionarily conserved nucleotides and have been eliminated from the older internal branches of the tree by purifying selection, while beneficial mutations also alter conserved nucleotides but have been enriched in the internal branches of the tree by adaptive selection. Neutral polymorphisms alter poorly conserved nucleotides and are distributed throughout the tree. Stem nucleotides are more constrained than loop nucleotides. The functional importance of both types of nucleotide variants was assessed by comparison to the average evolutionary conservation index (CI) of all known pathogenic tRNA mutations, thus permitting discrimination between internal branch neutral and adaptive tRNA variants. This revealed that 19% of the stem and 13% of the loop internal branch tRNA variants were potentially adaptive. Since few pathogenic rRNA mutations are known, evidence for adaptive rRNA variation was revealed by higher stem to loop variant ratios and elevated CIs in the internal branches vs. external branches. Moreover, variants among stem noncanonical apposition bases predominantly created new Watson-Crick (WC) base pairs, thus also suggesting adaptive selection. Among the putative adaptive tRNA and rRNA polymorphisms, a number were found to occur at the base of the branches of the tree, to have recurred multiple times, and to be associated with altered human phenotypes. Therefore, a significant portion of ancient tRNA and rRNA polymorphisms appear to have been adaptive, and these are affecting human health today. Hum Murat 27(11), 1072-1081, 2006. Published 2006 Wiley-Liss, Inc.