The Evolution of Gene Expression QTL in Saccharomyces cerevisiae

Understanding the evolutionary forces that influence patterns of gene expression variation will provide insights into the mechanisms of evolutionary change and the molecular basis of phenotypic diversity. To date, studies of gene expression evolution have primarily been made by analyzing how gene expression levels vary within and between species. However, the fundamental unit of heritable variation in transcript abundance is the underlying regulatory allele, and as a result it is necessary to understand gene expression evolution at the level of DNA sequence variation. Here we describe the evolutionary forces shaping patterns of genetic variation for 1206 cis-regulatory QTL identified in a cross between two divergent strains of Saccharomyces cerevisiae. We demonstrate that purifying selection against mildly deleterious alleles is the dominant force governing cis-regulatory evolution in S. cerevisiae and estimate the strength of selection. We also find that essential genes and genes with larger codon bias are subject to slightly stronger cis-regulatory constraint and that positive selection has played a role in the evolution of major trans-acting QTL.解析驱动基因表达变异模式的进化力量，可为进化改变的内在机制以及表型多样性的分子基础提供重要认知。迄今为止，基因表达进化相关研究主要通过分析基因表达水平在物种内部及物种间的变异模式展开。然而，转录本丰度可遗传变异的基本单位是其上游的调控等位基因，因此亟需在DNA序列变异层面解析基因表达的进化过程。本研究针对两株分化酿酒酵母（Saccharomyces cerevisiae）杂交组合中鉴定出的1206个顺式调控数量性状位点（cis-regulatory QTL），阐明了塑造其遗传变异模式的进化力量。研究表明，针对轻度有害等位基因的净化选择是酿酒酵母顺式调控进化的主导驱动力，并对选择强度进行了估算。此外，本研究还发现，必需基因以及密码子偏好性更强的基因受到的顺式调控约束更为严格，且正选择在主要反式作用数量性状位点（trans-acting QTL）的进化过程中扮演了重要角色。