Gene Expression Evolves under a House-of-Cards Model of Stabilizing Selection
Gene Expression Evolves under a House-of-Cards Model of Stabilizing Selection
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DOI：
10.1093/molbev/msv094
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发表时间：
2015-08-01
影响因子：
10.7
通讯作者：
Townsend, Jeffrey P.
中科院分区：
文献类型：
--
作者：
Hodgins-Davis, Andrea;Rice, Daniel P.;Townsend, Jeffrey P.
基因调控的差异被假设为表型进化的基础，但自然选择在塑造基因表达的分子表型中的作用仍有争议。为了解决基因表达的模式，进化需要对长时间尺度上的选择效应进行可行的理论预测。表型进化的进化定量遗传模型可以提供这样的预测，但这些预测依赖于突变和选择效应分布的基本假设，而这些假设是众所周知的难以解开的。在这里，我们利用不同的基因组数据集，包括自然遗传变异和突变积累线的表达谱，基因组突变率的经验估计，和遗传结构的推断，以区分对比假设的作用，稳定的选择和突变在塑造自然表达变异。我们的分析表明，基因表达演变的表型空间域很好地拟合的纸牌屋（HC）模型。虽然推断出的选择强度对控制基因表达的基因座的数量敏感，但该模型并不敏感。这些结果在从芽殖酵母到果蝇的进化时间中的一致性意味着这种模型是通用的，并且突变对基因表达的影响相对较大。基因表达性状的遗传结构的经验估计意味着选择对大多数基因的基因表达水平提供适度的限制，但调节进化的潜力很高。我们的预测使用的数据从实验室环境中应鼓励收集额外的数据集，允许更细致入微的参数化HC模型的基因表达。
Divergence in gene regulation is hypothesized to underlie much of phenotypic evolution, but the role of natural selection in shaping the molecular phenotype of gene expression continues to be debated. To resolve the mode of gene expression, evolution requires accessible theoretical predictions for the effect of selection over long timescales. Evolutionary quantitative genetic models of phenotypic evolution can provide such predictions, yet those predictions depend on the underlying hypotheses about the distributions of mutational and selective effects that are notoriously difficult to disentangle. Here, we draw on diverse genomic data sets including expression profiles of natural genetic variation and mutation accumulation lines, empirical estimates of genomic mutation rates, and inferences of genetic architecture to differentiate contrasting hypotheses for the roles of stabilizing selection and mutation in shaping natural expression variation. Our analysis suggests that gene expression evolves in a domain of phenotype space well fit by the House-of-Cards (HC) model. Although the strength of selection inferred is sensitive to the number of loci controlling gene expression, the model is not. The consistency of these results across evolutionary time from budding yeast through fruit fly implies that this model is general and that mutational effects on gene expression are relatively large. Empirical estimates of the genetic architecture of gene expression traits imply that selection provides modest constraints on gene expression levels for most genes, but that the potential for regulatory evolution is high. Our prediction using data from laboratory environments should encourage the collection of additional data sets allowing for more nuanced parameterizations of HC models for gene expression.