Changes in gene expression predictably shift and switch genetic interactions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 08 2019
29 08 2019
Historique:
received:
10
04
2019
accepted:
29
07
2019
entrez:
31
8
2019
pubmed:
31
8
2019
medline:
7
1
2020
Statut:
epublish
Résumé
Non-additive interactions between mutations occur extensively and also change across conditions, making genetic prediction a difficult challenge. To better understand the plasticity of genetic interactions (epistasis), we combine mutations in a single protein performing a single function (a transcriptional repressor inhibiting a target gene). Even in this minimal system, genetic interactions switch from positive (suppressive) to negative (enhancing) as the expression of the gene changes. These seemingly complicated changes can be predicted using a mathematical model that propagates the effects of mutations on protein folding to the cellular phenotype. More generally, changes in gene expression should be expected to alter the effects of mutations and how they interact whenever the relationship between expression and a phenotype is nonlinear, which is the case for most genes. These results have important implications for understanding genotype-phenotype maps and illustrate how changes in genetic interactions can often-but not always-be predicted by hierarchical mechanistic models.
Identifiants
pubmed: 31467279
doi: 10.1038/s41467-019-11735-3
pii: 10.1038/s41467-019-11735-3
pmc: PMC6715729
doi:
Substances chimiques
Repressor Proteins
0
Viral Regulatory and Accessory Proteins
0
phage repressor proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3886Commentaires et corrections
Type : ErratumIn
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