Compensatory trans-regulatory alleles minimizing variation in TDH3 expression are common within Saccharomyces cerevisiae.
Compensatory trans-regulatory alleles minimizing variation in TDH3 expression are common within Saccharomyces cerevisiae.
复制标题
补偿性反式调节等位基因可最大限度地减少 TDH3 表达的变异，这在酿酒酵母中很常见。
DOI：
10.1002/evl3.137
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发表时间：
2019
影响因子：
5
通讯作者：
Wittkopp,PatriciaJ
中科院分区：
文献类型：
--
作者：
Metzger,BrianPH;Wittkopp,PatriciaJ
基因表达的遗传变异在物种中很常见。这种变异的大部分是由于基因表达和转录的改变引起的基因外的遗传差异。这种反式调节变异通常是多基因的，单个变异通常影响很小，使得反式调节变异的遗传结构和进化研究具有挑战性。因此，关于反式调节变异的关键问题仍然存在，包括物种内反式调节变异的变异性，选择如何影响反式调节变异，以及反式调节变异如何分布在整个基因组和物种内。为了解决这些问题，我们分离并测量了56株酿酒酵母中影响TDH 3启动子活性的反式调节差异，发现反式调节背景对TDH 3启动子活性的影响约为2倍。将这种变化与基于突变效应的经验测量的中性模型oftrans-regulatory进化进行比较，发现尽管trans-regulatory背景的影响存在这种变化，但稳定选择限制了该物种内的trans-regulatory差异。利用一种功能强大的数量性状位点定位方法，我们在与一个共同的参考菌株杂交的三个杂交组合中，分别鉴定了1000个反式表达数量性状位点，表明调控变异比以前的研究表明的更多基因。改变表达的位点位于整个基因组中，并且许多位点是菌株特异性的。这种等位基因的分布和流行与最近关于复杂性状遗传结构的理论是一致的。在所有作图实验中，非参考菌株等位基因以相似的频率增加和减少TDH 3启动子活性，表明稳定选择保持了许多具有相反效应的反式作用变体。这种变化可能提供了原材料的补偿性进化和更大规模的监管重新布线中观察到的发展系统之间的物种漂移。
Heritable variation in gene expression is common within species. Much of this variation is due to genetic differences outside of the gene with altered expression and istrans-acting. Thistrans-regulatory variation is often polygenic, with individual variants typically having small effects, making the genetic architecture and evolution oftrans-regulatory variation challenging to study. Consequently, key questions abouttrans-regulatory variation remain, including the variability oftrans-regulatory variation within a species, how selection affectstrans-regulatory variation, and howtrans-regulatory variants are distributed throughout the genome and within a species. To address these questions, we isolated and measuredtrans-regulatory differences affectingTDH3promoter activity among 56 strains ofSaccharomyces cerevisiae, finding thattrans-regulatory backgrounds varied approximately twofold in their effects onTDH3promoter activity. Comparing this variation to neutral models oftrans-regulatory evolution based on empirical measures of mutational effects revealed that despite this variability in the effects oftrans-regulatory backgrounds, stabilizing selection has constrainedtrans-regulatory differences within this species. Using a powerful quantitative trait locus mapping method, we identified ∼100trans-acting expression quantitative trait locus in each of three crosses to a common reference strain, indicating that regulatory variation is more polygenic than previous studies have suggested. Loci altering expression were located throughout the genome, and many loci were strain specific. This distribution and prevalence of alleles is consistent with recent theories about the genetic architecture of complex traits. In all mapping experiments, the nonreference strain alleles increased and decreasedTDH3promoter activity with similar frequencies, suggesting that stabilizing selection maintained manytrans-acting variants with opposing effects. This variation may provide the raw material for compensatory evolution and larger scale regulatory rewiring observed in developmental systems drift among species.