Genome-wide survey of natural selection on functional, structural, and network properties of polymorphic sites in Saccharomyces paradoxus.
Genome-wide survey of natural selection on functional, structural, and network properties of polymorphic sites in Saccharomyces paradoxus.
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DOI：
10.1093/molbev/msr085
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发表时间：
2011-09
影响因子：
10.7
通讯作者：
A. Vishnoi;P. Sethupathy;D. Simola;J. Plotkin;S. Hannenhalli
中科院分区：
文献类型：
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作者：
A. Vishnoi;P. Sethupathy;D. Simola;J. Plotkin;S. Hannenhalli
背景：为了描述表型进化的遗传基础，许多研究已经确定了可能在自然选择下进化的单个基因。然而，表型变化可能代表了类似的进化力量作用于功能相关的基因群的累积效应。对不同酵母菌种的系统发育分析已经确定了以显著不同的速度进化的基因功能群，这表明在功能特性上存在差异选择。然而，由于在漫长的进化时间尺度上的环境异质性，在单一谱系中进行的选择可能会有很大的不同，而且仅通过种间比较是无法检测到的。此外，种间研究通常使用D(n)/D(s)比率来量化蛋白质编码区域的选择，这很难扩展到研究非编码区域或同义位点的选择。在单一谱系中进行的基于群体遗传学的选择分析改善了这些局限性。研究人员通过分析28株Saccharomyces paradoxus菌株的单核苷酸多态性（snp）等位基因频谱，研究了与基因、启动子或多态性位点相关的几种特性的选择。我们发现了许多功能相关类别的snp之间存在显著差异选择的证据，强调了以功能为中心的方法在发现自然选择特征方面的实用性。当比较时，我们的发现与先前基于种间比较的研究基本一致，但有一个值得注意的例外：我们的研究发现，从一个古老的氨基酸到一个相对新的氨基酸的突变是选择性地不利的，而种间比较发现选择不利于古老的氨基酸。我们的一些发现尚未通过先前的种间研究得到解决：我们发现从首选密码子到非首选密码子的同义突变被选择反对，并且蛋白质连接区域的同义snp相对较少受到蛋白质结构域内的约束。结论：我们提出了第一个全球调查的选择作用于各种功能性质的悖论。我们发现，以前在漫长的进化时间尺度上发现的选择压力也塑造了悖论螺的进化。重要的是，我们还通过传统的种间分析做出了新的发现。
BACKGROUND To characterize the genetic basis of phenotypic evolution, numerous studies have identified individual genes that have likely evolved under natural selection. However, phenotypic changes may represent the cumulative effect of similar evolutionary forces acting on functionally related groups of genes. Phylogenetic analyses of divergent yeast species have identified functional groups of genes that have evolved at significantly different rates, suggestive of differential selection on the functional properties. However, due to environmental heterogeneity over long evolutionary timescales, selection operating within a single lineage may be dramatically different, and it is not detectable via interspecific comparisons alone. Moreover, interspecific studies typically quantify selection on protein-coding regions using the D(n)/D(s) ratio, which cannot be extended easily to study selection on noncoding regions or synonymous sites. The population genetic-based analysis of selection operating within a single lineage ameliorates these limitations. FINDINGS We investigated selection on several properties associated with genes, promoters, or polymorphic sites, by analyzing the derived allele frequency spectrum of single nucleotide polymorphisms (SNPs) in 28 strains of Saccharomyces paradoxus. We found evidence for significant differential selection between many functionally relevant categories of SNPs, underscoring the utility of function-centric approaches for discovering signatures of natural selection. When comparable, our findings are largely consistent with previous studies based on interspecific comparisons, with one notable exception: our study finds that mutations from an ancient amino acid to a relatively new amino acid are selectively disfavored, whereas interspecific comparisons have found selection against ancient amino acids. Several of our findings have not been addressed through prior interspecific studies: we find that synonymous mutations from preferred to unpreferred codons are selected against and that synonymous SNPs in the linker regions of proteins are relatively less constrained than those within protein domains. CONCLUSIONS We present the first global survey of selection acting on various functional properties in S. paradoxus. We found that selection pressures previously detected over long evolutionary timescales have also shaped the evolution of S. paradoxus. Importantly, we also make novel discoveries untenable via conventional interspecific analyses.