Genetic Influences on Translation in Yeast
Genetic Influences on Translation in Yeast
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DOI：
10.1371/journal.pgen.1004692
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发表时间：
2014-10-01
期刊：
影响因子：
4.5
通讯作者：
Kruglyak, Leonid
中科院分区：
文献类型：
--
作者：
Albert, Frank W.;Muzzey, Dale;Kruglyak, Leonid
个体之间基因表达的遗传差异是表型变异的重要来源。遗传变异对蛋白质水平的影响与 mRNA 水平的影响有多密切这一问题仍然悬而未决。在这里，我们通过使用核糖体分析来检查两种酿酒酵母菌株之间的遗传差异如何影响翻译来解决这个问题。观察到数百个基因的翻译差异。两个菌株之间的二倍体杂种的等位基因特异性测量显示，对翻译的顺式作用影响大约是在 mRNA 水平上观察到的一半。在亲本和杂种中，对翻译的大多数影响都很小，因此 mRNA 差异的方向通常反映在一致的足迹差异中。顺式和反式作用变异对足迹水平的相对重要性与 mRNA 水平的相对重要性相似。鉴于各自 mRNA 的差异，翻译倾向于导致比预期更大的足迹差异。这与酵母物种之间的翻译差异形成鲜明对比，据报道，酵母物种之间的翻译差异往往会阻碍而不是加强 mRNA 差异。最后，我们对两种酵母菌株中过早翻译终止的实例进行了编目，还发现了几个实例，其中错误的参考基因注释导致明显的无义突变，这些突变实际上位于翻译的基因体之外。总体而言，遗传对翻译的影响微妙地调节了基因表达差异，并且翻译不会在遗传对 mRNA 和蛋白质水平的影响之间产生强烈的差异。
Heritable differences in gene expression between individuals are an important source of phenotypic variation. The question of how closely the effects of genetic variation on protein levels mirror those on mRNA levels remains open. Here, we addressed this question by using ribosome profiling to examine how genetic differences between two strains of the yeast S. cerevisiae affect translation. Strain differences in translation were observed for hundreds of genes. Allele specific measurements in the diploid hybrid between the two strains revealed roughly half as many cis-acting effects on translation as were observed for mRNA levels. In both the parents and the hybrid, most effects on translation were of small magnitude, such that the direction of an mRNA difference was typically reflected in a concordant footprint difference. The relative importance of cis and trans acting variation on footprint levels was similar to that for mRNA levels. There was a tendency for translation to cause larger footprint differences than expected given the respective mRNA differences. This is in contrast to translational differences between yeast species that have been reported to more often oppose than reinforce mRNA differences. Finally, we catalogued instances of premature translation termination in the two yeast strains and also found several instances where erroneous reference gene annotations lead to apparent nonsense mutations that in fact reside outside of the translated gene body. Overall, genetic influences on translation subtly modulate gene expression differences, and translation does not create strong discrepancies between genetic influences on mRNA and protein levels.