Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites
Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites
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DOI：
10.1016/j.jtbi.2005.10.020
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发表时间：
2006-06-21
影响因子：
2
通讯作者：
Kondrashov, Alexey S.
中科院分区：
文献类型：
--
作者：
Kondrashov, Fyodor A.;Ogurtsov, Aleksey Y.;Kondrashov, Alexey S.
同义核苷酸替换对哺乳动物适应性的影响仍然存在争议。尽管有一些选择性约束的迹象，同义位点通常被认为是中性的，它们的进化速度被用作突变率的代表。我们根据可变的CpG上下文将所有位点细分为四类：nonCpG、postC、preG和postCpreG，并比较了四倍同义位点和位于转座元件外的内含子位点。所有同义地点的进化速率分布是三模态的。非cpg同义位点（前面没有C，后面也没有G）的进化速率比内含子位点低10%。相比之下，cpreg后同义位点的进化率比内含子位点高30%。最后，同义和内含子的后c和前g位点以相似的速率进化。在相应的同义位点和内含子位点的多态性水平之间的关系与它们的进化速度之间的关系非常相似。在每一类中，同义位点被G或C占据的频率远高于内含子位点，其核苷酸组成符合中性突变-漂移平衡。这些模式表明同音位点处于弱选择状态，有利于G和C，平均系数s近似于0.25/N-e近似于10(-5)，其中Ne为有效种群大小。这样的选择减缓了进化，减少了对称突变位点的变异，但在更易变的核苷酸位点则产生相反的效果。蛋白质的氨基酸组成决定了许多同义位点是CpGprone，这导致它们平均而言比内含子位点进化得更快，更具多态性。一个平均基因型在同义位点携带大约10(7)个次优核苷酸，这意味着在选择中对它们具有协同上位性。Elsevier Ltd.出版。
The impact of synonymous nucleotide substitutions on fitness in mammals remains controversial. Despite some indications of selective constraint, synonymous sites are often assumed to be neutral, and the rate of their evolution is used as a proxy for mutation rate. We subdivide all sites into four classes in terms of the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold synonymous sites and intron sites residing outside transposable elements. The distribution of the rate of evolution across all synonymous sites is trimodal. Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed by G, is similar to 10% below that at such intron sites. In contrast, rate of evolution at postCpreG synonymous sites is similar to 30% above that at such intron sites. Finally, synonymous and intron postC and preG sites evolve at similar rates. The relationship between the levels of polymorphism at the corresponding synonymous and intron sites is very similar to that between their rates of evolution. Within every class, synonymous sites are occupied by G or C much more often than intron sites, whose nucleotide composition is consistent with neutral mutation-drift equilibrium. These patterns suggest that synonymous sites are under weak selection in favor of G and C, with the average coefficient s similar to 0.25/N-e similar to 10(-5), where Ne is the effective population size. Such selection decelerates evolution and reduces variability at sites with symmetric mutation, but has the opposite effects at sites where the favored nucleotides are more mutable. The amino-acid composition of proteins dictates that many synonymous sites are CpGprone, which causes them, on average, to evolve faster and to be more polymorphic than intron sites. An average genotype carries similar to 10(7) suboptimal nucleotides at synonymous sites, implying synergistic epistasis in selection against them. Published by Elsevier Ltd.