UMR 7156 Génétique Moléculaire, Génomique et Microbiologie, Université de Strasbourg, CNRS, Strasbourg 67000, France.
The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom.
Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2319211121. doi: 10.1073/pnas.2319211121. Epub 2024 May 2.
Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein coexpression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship.
基因表达在个体之间存在差异,对应于将基因型与表型联系起来的关键步骤。然而,我们对于蛋白质丰度的全物种遗传控制,包括其对转录水平的依赖性的了解非常有限。在这里,我们已经确定了 942 个多样化的天然酵母分离物的大型群体的定量蛋白质组。我们发现,mRNA 和蛋白质丰度在群体基因水平上相关性较弱。虽然蛋白质共表达网络再现了主要的生物学功能,但差异表达模式揭示了与特定群体相关的蛋白质组学特征。全面的遗传关联分析突出表明,与蛋白质(pQTL)和转录物(eQTL)水平变化相关的遗传变异很少重叠(3%)。我们的结果表明,转录组和蛋白质组受不同的遗传基础控制,这可能是由蛋白质周转解释的。它还强调了整合这些不同层次的基因表达以更好地理解基因型-表型关系的重要性。