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

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2319211121. doi: 10.1073/pnas.2319211121. Epub 2024 May 2.

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.

Keywords: gene regulation; genetic control; pQTL; quantitative proteomes; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Fungal*
  • Genetic Variation
  • Genotype
  • Phenotype
  • Proteome* / genetics
  • Proteome* / metabolism
  • Proteomics / methods
  • Quantitative Trait Loci*
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Transcriptome*

Substances

  • Proteome
  • Saccharomyces cerevisiae Proteins