Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness
Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness
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DOI：
10.1038/nature08691
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发表时间：
2010-03-11
期刊：
影响因子：
64.8
通讯作者：
Kondrashov, Fyodor A.
中科院分区：
文献类型：
--
作者：
Meer, Margarita V.;Kondrashov, Alexey S.;Kondrashov, Fyodor A.
进化生物学中一个长期存在的争议是，进化谱系是否可以跨越低适应度基因型的适应度低谷，从而最终使它们达到孤立的适应度峰值（1-9）。本文研究了83种哺乳动物线粒体转移RNA干区互补位点不同AU和GC沃森-克里克核苷酸对切换所经历的适应度景观。我们发现这种沃森-克里克开关的发生速度比对中性替换慢30-40倍，并且与GU和AC非沃森-克里克中间状态相对应的等位基因在人群中以低频率分离，类似于非同音等位基因。导致沃森克里克开关的替换是密切相关的，特别是在线粒体基因组富含gt核苷酸链上编码的线粒体trna中。使用这些数据，我们估计典型的沃森-克里克开关涉及跨越深度约为10（-3）甚至约为10（-2）的适应度谷，其中AC中间体比GU中间体稍微更有害。这种代偿性进化必须通过罕见的中间变异进行，这些中间变异从未达到固定状态(2)。哺乳动物线粒体trna和其他分子中普遍存在的代偿性进化（10,11）表明，在分子水平上，同时固定两个单独有害的等位基因可能是一种普遍现象。
A long-standing controversy in evolutionary biology is whether or not evolving lineages can cross valleys on the fitness landscape that correspond to low-fitness genotypes, which can eventually enable them to reach isolated fitness peaks(1-9). Here we study the fitness landscapes traversed by switches between different AU and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles corresponding to GU and AC non-Watson-Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles. Substitutions leading to a Watson Crick switch are strongly correlated, especially in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial genome. Using these data we estimate that a typical Watson-Crick switch involves crossing a fitness valley of a depth of about 10(-3) or even about 10(-2), with AC intermediates being slightly more deleterious than GU intermediates. This compensatory evolution must proceed through rare intermediate variants that never reach fixation(2). The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules(10,11) implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.