Genetic effects on molecular network states explain complex traits
File(s)
Author(s)
Type
Journal Article
Abstract
The complexity of many cellular and organismal traits results from the integration of genetic and environmental factors via molecular networks. Network structure and effect propagation are best understood at the level of functional modules, but so far, no concept has been established to include the global network state. Here, we show when and how genetic perturbations lead to molecular changes that are confined to small parts of a network versus when they lead to modulation of network states. Integrating multi‐omics profiling of genetically heterogeneous budding and fission yeast strains with an array of cellular traits identified a central state transition of the yeast molecular network that is related to PKA and TOR (PT) signaling. Genetic variants affecting this PT state globally shifted the molecular network along a single‐dimensional axis, thereby modulating processes including energy and amino acid metabolism, transcription, translation, cell cycle control, and cellular stress response. We propose that genetic effects can propagate through large parts of molecular networks because of the functional requirement to centrally coordinate the activity of fundamental cellular processes.
Date Issued
2023-08-08
Date Acceptance
2023-07-04
Citation
Molecular Systems Biology, 2023, 19 (8)
ISSN
1744-4292
Publisher
EMBOpress
Journal / Book Title
Molecular Systems Biology
Volume
19
Issue
8
Copyright Statement
© 2023 The Authors. Published under the terms of the CC BY 4.0 license
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:001033738700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Biochemistry & Molecular Biology
complex traits
COORDINATION
EXPRESSION
FUNCTIONAL GENOMICS
GROWTH
Life Sciences & Biomedicine
METABOLISM
MULTIPLE
network effects
PHOSPHORYLATION
PKA signaling
PROTEIN-KINASE-A
QTL mapping
Science & Technology
TOR
TOR signaling
YEAST
Publication Status
Published
Article Number
e11493
Date Publish Online
2023-07-24