Species-wide quantitative transcriptomes and proteomes reveal distinct genetic control of gene expression variation in yeast

Author:

Teyssonnière Elie Marcel1,Trébulle Pauline2,Muenzner Julia3,Loegler Victor1,Ludwig Daniela34,Amari Fatma34,Mülleder Michael4,Friedrich Anne1ORCID,Hou Jing1,Ralser Markus235,Schacherer Joseph16ORCID

Affiliation:

1. UMR 7156 Génétique Moléculaire, Génomique et Microbiologie, Université de Strasbourg, CNRS, Strasbourg 67000, France

2. The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom

3. Department of Biochemistry, Charitéplatz 1, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany

4. Core Facility High-Throughput Mass Spectrometry, Charitéplatz 1, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany

5. Max Planck Institute for Molecular Genetics, Berlin 14195, Germany

6. Institut Universitaire de France, Paris 75000, France

Abstract

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 Saccharomyces cerevisiae 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.

Funder

HHS | National Institutes of Health

EC | ERC | HORIZON EUROPE European Research Council

Wellcome Trust

Publisher

Proceedings of the National Academy of Sciences

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