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Epistasis as the primary factor in molecular evolution

机译：上位性是分子进化的主要因素

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摘要

在这篇论文中，Fyodor KondrasPiov及其同事对演化中被“上位效应”影响的氨基酸取代部分提供了定量估计。“上位效应”指在一个遗传背景基因型下被接受的取代在另一个中是有害的情形。对所选择的细胞器基因和核基因的一千多个直系同源基因所做比较显示，最近演化中的氨基酸取代速度要比中性演化的速度慢20倍，比在没有“上位效应”时所预期的速度慢一个数量级。这些结果表明，绝大多数氨基酸取代在不同物种中有不同适应性影响，“上位效应”为描述长期蛋白演化的模式和节奏提供了基本概念框架。%The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection1"4, 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.
机译：在这篇论文中，Fyodor KondrasPiov及其同事对演化中被“上位效应”影响的氨基酸取代部分提供了定量估计。“上位效应”指在一个遗传背景基因型下被接受的取代在另一个中是有害的情形。对所选择的细胞器基因和核基因的一千多个直系同源基因所做比较显示，最近演化中的氨基酸取代速度要比中性演化的速度慢20倍，比在没有“上位效应”时所预期的速度慢一个数量级。这些结果表明，绝大多数氨基酸取代在不同物种中有不同适应性影响，“上位效应”为描述长期蛋白演化的模式和节奏提供了基本概念框架。%The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection1"4, 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.

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  • 来源
    《Nature》 |2012年第7421期|p.535-538A3|共5页
  • 作者

    Michael S. Breen; Carsten Kemena; Peter K. Vlasov; Cedric Notredame; Fyodor A. Kondrashov;

  • 作者单位

    Bioinformatics and Genomics Programme, Centre for Genomic Regulation and Universitat Pompeu Fabra, 88 Dr Aiguader, Barcelona 08003, Spain;

    Bioinformatics and Genomics Programme, Centre for Genomic Regulation and Universitat Pompeu Fabra, 88 Dr Aiguader, Barcelona 08003, Spain;

    Bioinformatics and Genomics Programme, Centre for Genomic Regulation and Universitat Pompeu Fabra, 88 Dr Aiguader, Barcelona 08003, Spain;

    Bioinformatics and Genomics Programme, Centre for Genomic Regulation and Universitat Pompeu Fabra, 88 Dr Aiguader, Barcelona 08003, Spain;

    lnstituci6 Catalana de Recerca i Estudis Avancats (ICREA), 23 Passeig Lluis Companys, Barcelona 08010, Spain Bioinformatics and Genomics Programme, Centre for Genomic Regulation and Universitat Pompeu Fabra, 88 Dr Aiguader, Barcelona 08003, Spain;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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