来自西班牙法普拉大学的科学家日前通过研究表明近期进化中氨基酸替换率比在上位性缺乏中期望的要低一个数量级,表明基因上位性在蛋白进化过程中普遍存在。

-2012年10月25日《自然》


中文翻译


【题目】上位性是分子进化的主要因素

【译文】推动长期分子进化的主导力尚不清楚。 相当大部分的氨基酸替换似乎由位置选择性所固定,但还不清楚长期蛋白进化被上位性束缚的程度,也就是说,当在一种表型中被接收的替换在另一种表型中却是有害的。本研究利用14个细胞器蛋白中的氨基酸利用和2个核编码蛋白的数据结合它们短期进化率的数据,对长期蛋白进化过程中上位性的存在率做个定量评估。我们对这16个蛋白中每一个的至少1000个来自不同种系发育背景物种的同源基因进行多重序列比对,结果发现一个等位位点大约含有8个不同的氨基酸。因此,没有上位性,一个等位位点应该接受所有可能氨基酸的五分之二,并且氨基酸替换的平均率应该因此比中性进化低五分之三。然而,我们发现近期进化中氨基酸替换的测量值是中性进化的20倍,比期望的上位性缺失低了一个数量级。这些数据表明上位性遍布蛋白质的整个进化过程中:约90%的氨基酸替换仅在遗传背景中具有中性或有益的影响,而且因此必定在其他物种的不同背景下是有害的。我们的发现表明大多数氨基酸替换在不同物种中具有不同的适应效应,而上位性提供了描述长期蛋白进化速度和模式的基本概念框架。

英文原稿


[Title]: Epistasis as the primary factor in molecular evolution

[Authors]:Michael S. Breen,1 Carsten Kemena,1 Peter K. Vlasov,1 Cedric Notredame1 & Fyodor A. Kondrashov1, 2

[Abstract]The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.

原文地址

http://www.nature.com/nature/journal/v490/n7421/full/nature11510.html

 

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