Open AccessThe impact of genomic variation on protein phosphorylation states and regulatory networks
Author(s) -
Grossbach Jan,
Gillet Ludovic,
ClémentZiza Mathieu,
Schmalohr Corinna L,
Schubert Olga T,
Schütter Maximilian,
Mawer Julia S P,
Barnes Christopher A,
Bludau Isabell,
Weith Matthias,
Tessarz Peter,
Graef Martin,
Aebersold Ruedi,
Beyer Andreas
Publication year - 2022
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.202110712
Subject(s) - biology , variation (astronomy) , phosphorylation , computational biology , genetics , genomics , gene , genome , physics , astrophysics
Genomic variation impacts on cellular networks by affecting the abundance (e.g., protein levels) and the functional states (e.g., protein phosphorylation) of their components. Previous work has focused on the former, while in this context, the functional states of proteins have largely remained neglected. Here, we generated high‐quality transcriptome, proteome, and phosphoproteome data for a panel of 112 genomically well‐defined yeast strains. Genetic effects on transcripts were generally transmitted to the protein layer, but specific gene groups, such as ribosomal proteins, showed diverging effects on protein levels compared with RNA levels. Phosphorylation states proved crucial to unravel genetic effects on signaling networks. Correspondingly, genetic variants that cause phosphorylation changes were mostly different from those causing abundance changes in the respective proteins. Underscoring their relevance for cell physiology, phosphorylation traits were more strongly correlated with cell physiological traits such as chemical compound resistance or cell morphology, compared with transcript or protein abundance. This study demonstrates how molecular networks mediate the effects of genomic variants to cellular traits and highlights the particular importance of protein phosphorylation.