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首页> 外文期刊>PLoS Genetics >The Impact of the Nucleosome Code on Protein-Coding Sequence Evolution in Yeast
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The Impact of the Nucleosome Code on Protein-Coding Sequence Evolution in Yeast

机译：核小体编码对酵母中蛋白质编码序列进化的影响

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Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free “linker” sequence to evolve on average 5–6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5′ end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread.
机译：编码序列的进化曾经被认为是单独选择最佳蛋白质功能的结果。但是，选择也可以在RNA水平起作用，例如，以促进快速翻译或确保正确的剪接。在这里，我们询问DNA的工作方式是否也对编码序列的进化施加了限制。我们确定核小体定位为可能建立这种DNA水平的选择制度的候选人，并在酵母中使用高分辨率的微阵列数据来比较与核小体结合或无核小体的编码序列的进化。控制基因表达和基因内位置，我们发现一个无核小体的“连接子”序列在同义位点处平均慢5–6％的进化。接头进化速度的降低在基因的5'端尤为明显，其影响延伸至非同义替代率。这与该区域中规则的核小体结构是一致的，这在基因表达控制的背景下是重要的。如所预测的，可能产生不利于核小体形成的序列的密码子富含接头序列。氨基酸含量也随着核小体的占有率而偏斜。我们得出结论，对DNA进行操作以维持核小体的正确定位的选择会影响密码子选择，氨基酸选择以及编码序列中同义和非同义进化速率。结果支持核小体定位的排除模型，并提供稀有密码子运行的替代解释。由于组蛋白和DNA的紧密结合是真核生物基因序列的普遍特征，因此，由核小体定位施加的编码序列组成的选择应在系统发育上广泛分布。

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