The Roles of Mutation, Selection, and Expression in Determining Relative Rates of Evolution in Mitochondrial versus Nuclear Genomes
The Roles of Mutation, Selection, and Expression in Determining Relative Rates of Evolution in Mitochondrial versus Nuclear Genomes
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DOI：
10.1093/molbev/msw185
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发表时间：
2016-12-01
影响因子：
10.7
通讯作者：
Sloan，Daniel B.
中科院分区：
文献类型：
--
作者：
Havird，Justin C.;Sloan，Daniel B.
真核生物依赖于由核和线粒体（mt）基因组编码的蛋白质，这些蛋白质在多亚基复合体（如氧化磷酸化酶）中相互作用。虽然选择被认为在无性mt基因组上效率较低，但在双侧性动物中，与核编码的OXPHOS亚基相比，mt-中的非同义与同义取代的比率（ω）较低，这表明mt基因组中纯化选择的效果较强。由于高水平的基因表达限制了蛋白质序列的进化，因此有人提出解决这一矛盾的方法，即mt基因比核基因表达更高。为了验证这一假设，我们研究了84种不同真核生物mt基因含量和突变率不同的mt和核基因的表达和序列进化。我们发现mt和核ω值之间的关系在真核生物中变化很大。与此相反，转录丰度始终较高的mt基因比核基因，无论哪些基因发生在mt基因组。因此，表达水平不能对ω的差异负责。相反，mt和核基因之间ω值比值的84%的方差可以通过两个基因组之间突变率的差异来解释。我们将这些发现与高比率的mt突变选择核基因组中的补偿性变化的假设联系起来。我们还提出了一个解释，为什么线粒体转录本始终超过他们的核同行，与线粒体蛋白质失衡和衰老的影响。
Eukaryotes rely on proteins encoded by the nuclear and mitochondrial (mt) genomes, which interact within multisubunit complexes such as oxidative-phosphorylation enzymes. Although selection is thought to be less efficient on the asexual mt genome, in bilaterian animals the ratio of nonsynonymous to synonymous substitutions (ω) is lower in mt- compared with nuclear-encoded OXPHOS subunits, suggestingstrongereffects of purifying selection in the mt genome. Because high levels of gene expression constrain protein sequence evolution, one proposed resolution to this paradox is that mt genes are expressed more highly than nuclear genes. To test this hypothesis, we investigated expression and sequence evolution of mt and nuclear genes from 84 diverse eukaryotes that vary in mt gene content and mutation rate. We found that the relationship between mt and nuclearωvalues varied dramatically across eukaryotes. In contrast, transcript abundance is consistently higher for mt genes than nuclear genes, regardless of which genes happen to be in the mt genome. Consequently, expression levels cannot be responsible for the differences inω. Rather, 84% of the variance in the ratio ofωvalues between mt and nuclear genes could be explained by differences in mutation rate between the two genomes. We relate these findings to the hypothesis that high rates of mt mutation select for compensatory changes in the nuclear genome. We also propose an explanation for why mt transcripts consistently outnumber their nuclear counterparts, with implications for mitonuclear protein imbalance and aging.