# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz These results imply that, early in their evolutionary history, duplicate genes tend to be under moderate selective constraints with the rate of amino acid substitution averaging about 43% of the neutral expectation. The efficiency of purifying selection subsequently increases approximately 10-fold, to the point at which only about 5% of amino acid–changing mutations are able to rise to fixation. 这些结果表明，重复基因在其进化史的早期，往往处于中等选择性的约束下，氨基酸替代率平均约为 43% ，接近中性预期。纯化选择的效率随后增加约 10 倍，到只有约 5% 的改变氨基酸的突变能够被固定的程度。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155.
# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz Under the assumption that silent substitutions are largely immune from selection and accumulate at a stochastic rate that is proportional to time, we take the number of substitutions per silent site, S, separating two members of a pair of duplicates to be a measure of the relative age of the pair. Letting R denote the number of substitutions per replacement site, a net (cumulative) selective constraint since the time of origin of a pair of duplicates will be reflected in an R/S ratio 1, whereas a net acceleration of protein evolution will be revealed by an R/S ratio 1. Complete relaxation of selection will result in R/S ≈ 1. For the duplicate genes that we have identified, there is often considerable scatter around the neutral expectation when S 0.05 (Fig. 1), suggesting that early in their history, many gene duplicates experience a phase of relaxed selection or even accelerated evolution at replacement sites. The progressive decline of R/S beyond this point reflects a gradual increase in the magnitude of selective constraint. The vast majority of gene duplicates with S 0.1 exhibits an R/S ratio 1. 假设沉默突变在很大程度上不受选择的影响，并且以与时间成正比的随机速率累积，我们取每个沉默位点的替换数为 S 。将 S 作为一对重复基因分化相对时间的度量。如果 R 表示每个错义突变位点的替换数量，则自一对重复基因产生开始的净（累积）选择性约束将反映为 R/S 1 中，而蛋白质进化的发生由 R/S 1 表示。完全的松弛选择将导致 R/S ≈ 1 。对于我们已经鉴定的重复基因，当 S0.05 （图 1 ）时，通常在中性预期周围有相当大的散点分布，这表明在它们的历史早期，许多基因重复经历了一个宽松的选择阶段，甚至在错义突变位点加速进化。超过这一点的 R/S 的逐渐下降反映了选择性约束的程度逐渐增加。当 S0.1 时绝大多数基因重复序列的 R/S 比小于 1 。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155.
# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz The traditional approach to inferring the magnitude of selective constraint on protein evolution focuses on codons, comparing the rates of nucleotide substitution at replacement and silent sites (7, 15, 16). With this sort of analysis, only the cumulative pattern of nucleotide substitution is identified, making it difficult to determine whether duplicate genes typically undergo different phases of evolutionary divergence, e.g., an early phase of near neutrality followed by a later phase of selective constraint. Some clarification of this issue can be achieved by considering the features of sets of gene duplicates separated by an array of divergence times. 传统的推断蛋白质进化的选择性限制的方法集中在密码子上，比较功能变化位点和沉默位点的核苷酸替换比率（ 7 ， 15 ， 16 ）。通过这种分析，仅识别出核苷酸替换的累积模式，使得很难确定重复基因是否典型地经历不同的进化分化阶段，例如，接近中性的早期阶段，随后是选择性限制的后期阶段。通过考虑由一系列分化时间不同的重复基因（见编者注），可以对这个问题进行一些澄清。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155. （编者注：某一时刻，可以检测到很多组不同的重复基因，不同的重复基因产生的时间点有所不同，这样就可观察到在不同的分化时间阶段，重复基因的不同表现。就好比，要观察人类的一生，可以采用选取某个时点上，婴儿、孩童、青春期少年、青年、中年、老年等人群来了解人的一生不同阶段的具体表现）
# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz Further insight into the rates of origin of.duplicate genes and their evolutionary fates can now be acquired by using the genomic databases that have emerged for several species. We focused on nine taxa for which large numbers of protein-coding sequences are available through electronic databases: human (Homo sapiens), mouse (Mus musculus), chicken (Gallus gallus), nematode (Caenorhabditis elegans), fly(Drosophila melanogaster), the plants Arabidopsis thaliana and Oryza sativa (rice), and the yeast Saccharomyces cerevisiae. For each of.these species, the complete set of available open reading frames was screened to eliminate sequences that were unlikely to be functional. proteins (21). Each sequence retained after this initial filtering was then compared against all other members of the intraspecific set to identify pairs of gene duplicates, which were then analyzed for the degree of nucleotide divergence (21). The analyses for C. elegans, D. melanogaster, and S. cerevisiae were based on the complete genomic sequences available for these species.. 现在可以通过使用已经出现的几个物种的基因组数据库来进一步了解重复基因的发生率及其进化命运。我们重点研究了 9 个类群的基因组电子数据库，其中有大量的蛋白质编码序列。这个类群分别是：人类（ Homo sapiens ）、小鼠（ Mus musculus ）、鸡（ Gallus Gallus ）、线虫（ Caenorhabditis elegans ）、果蝇（ Drosophila melanogaste ）、拟南芥（ Arabidopsis thaliana ）、水稻（ Oryza sativa ）和酿酒酵母（ Saccharo myces cerevisiae ）。对于其中每一个物种，筛选出一整套可用的开放式阅读框，以消除不可能是功能性蛋白质的序列（ 21 ）。然后，将初始筛选后保留的每个序列与组内的所有其他成员进行比较，以识别成对的基因重复，然后分析这些重复的核苷酸差异程度（ 21 ）。对线虫、黑腹果蝇和酿酒酵母的分析基于这些物种的完整基因组序列。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155.
# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz These theoretical expectations are only partially consistent with the limited data that we have on gene duplication. First, comparative studies of nucleotide sequences suggest that although both copies of a gene may often accumulate degenerative mutations at an accelerated rate following a duplication event, selection may not be relaxed completely (14– 16). Second, the frequency of duplicate-gene preservation following ancient polyploidization events, often suggested to be in the neighborhood of 30 to 50% over periods of tens to hundreds of millions of years (17–20), is unexpectedly high. 这些理论假设只是部分地与我们在基因复制方面的有限数据相一致。首先，对核苷酸序列的比较研究表明，尽管一个基因的两个拷贝在重复事件发生后往往会加速积累退行性突变，但选择压力可能不会完全放松（ 14-16 ）。第二，在古代多倍体化事件之后，在几千万到数亿年（ 17-20 年）的时间里，重复基因的保存频率出人意料地高，通常被认为大约在 30% 到 50% 。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155.
# 编者信息 熊荣川 明湖实验室 xiongrongchuan@126.com http://blog.sciencenet.cn/u/Bearjazz Theory suggests three alternative outcomes in the evolution of duplicate genes: (i) one copy may simply become silenced by degenerative mutations (nonfunctionalization); (ii) one copy may acquire a novel, beneficial function and become preserved by natural selection, with the other copy retaining the original function (neofunctionalization); or (iii) both copies may become partially compromised by mutation accumulation to the point at which their total capacity is reduced to the level of the single-copy ancestral gene (subfunctionalization) (1–12). Because the vast majority of mutations affecting fitness are deleterious (13), and because gene duplicates are generally assumed to be functionally redundant at the time of origin, virtually all models predict that the usual fate of a duplicate-gene pair is the nonfunctionalization of one copy. The expected time that elapses before a gene is silenced is thought to be relatively short, on the order of the reciprocal of the null mutation rate per locus (a few million years or less), except in populations with enormous effective sizes (11, 12). 理论表明，在重复基因的进化过程中，有三种不同的结果：（ i ）一个拷贝可能被退化的突变（非功能化）所沉默；（ ii ）一个拷贝可能获得一种新的、有益的功能（新功能化），并被自然选择所保留，而另一个拷贝则保留了原来的功能；或（ iii ）两个拷贝可能因突变累积而部分表达，直至其总容量降低到单拷贝祖先基因的水平（子功能化）（ 1-12 ）。因为影响适应能力的绝大多数突变是有害的（ 13 ），并且由于基因重复在起源时通常被认为是功能上的冗余，几乎所有的模型都预测一个重复基因对的通常命运是一个拷贝的非功能化。除了具有巨大个体数的群体（ 11 ， 12 ），考虑每个基因座的不同无义突变率级别（几百万年或更少），基因沉默前的预期时间被认为是相对较短的。 Lynch, M. The Evolutionary Fate and Consequences of Duplicate Genes . Science, 2000, 290(5494):1151-1155.
标签: 复制基因
