Maximum likelihood methods for detecting adaptive protein evolution
Maximum likelihood methods for detecting adaptive protein evolution
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DOI：
10.1007/0-387-27733-1_5
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Yang, ZH
中科院分区：
文献类型：
--
作者：
Bielawski, JP;Yang, ZH
蛋白质进化;编码它们的基因经历突变，新突变的进化命运由随机遗传漂变以及净化或正（达尔文）选择决定。分析这一过程的能力是在20世纪70年代后期实现的，当时开发了在序列水平上测量遗传变异的技术。分子序列数据的到来也加剧了关于中性漂变和正选择对分子进化过程的相对重要性的争论[17]。从那以后，人们对记录分子适应的案例产生了相当大的兴趣。尽管自20世纪70年代以来，可用的核苷酸序列数据量有了惊人的增长，但此类已确立的病例数量仍然相对较少[9，38]。这很大程度上是由于难以开发针对适应性分子进化的强大统计测试。虽然已经开发了几种强有力的非中性进化测试[33]，但在这些测试下的显著结果并不一定表明通过正选择进行的进化。通过正选择检测分子进化的一种强有力的方法来自同义和非同义取代的相对速率的比较[22]。同义突变不改变氨基酸序列;因此它们的取代率（dS）相对于基因蛋白产物的选择压力是中性的。非同义突变确实改变了氨基酸序列，因此它们的取代率（dN）是蛋白质选择压力的函数。这些速率的比率（ω= dN/dS）是选择压力的量度。例如，如果非同义突变是有害的，则纯化选择将降低它们的固定速率，并且dN/dS将小于1，而如果非同义突变是有利的，则它们将以比同义突变更高的速率被固定，并且dN/dS将大于1。dN/dS比等于1符合中性演化。
Proteins evolve; the genes encoding them undergo mutation, and the evolutionary fate of the new mutation is determined by random genetic drift as well as purifying or positive (Darwinian) selection. The ability to analyze this process was realized in the late 1970s when techniques to measure genetic variation at the sequence level were developed. The arrival of molecular sequence data also intensified the debate concerning the relative importance of neutral drift and positive selection to the process of molecular evolution [17]. Ever since, there has been considerable interest in documenting cases of molecular adaptation. Despite a spectacular increase in the amount of available nucleotide sequence data since the 1970s, the number of such well-established cases is still relatively small [9, 38]. This is largely due to the difficulty in developing powerful statistical tests for adaptive molecular evolution. Although several powerful tests for nonneutral evolution have been developed [33], significant results under such tests do not necessarily indicate evolution by positive selection.A powerful approach to detecting molecular evolution by positive selection derives from comparison of the relative rates of synonymous and nonsynonymous substitutions [22]. Synonymous mutations do not change the amino acid sequence; hence their substitution rate (dS) is neutral with respect to selective pressure on the protein product of a gene. Nonsynonymous mutations do change the amino acid sequence, so their substitution rate (dN) is a function of selective pressure on the protein. The ratio of these rates (ω= dN/dS) is a measure of selective pressure. For example, if nonsynonymous mutations are deleterious, purifying selection will reduce their fixation rate and dN/dS will be less than 1, whereas if nonsynonymous mutations are advantageous, they will be fixed at a higher rate than synonymous mutations, and dN/dS will be greater than 1. A dN/dS ratio equal to one is consistent with neutral evolution.