Deep mutational scanning reveals the molecular determinants of RNA polymerase-mediated adaptation and tradeoffs.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 10 2023
09 10 2023
Historique:
received:
23
02
2023
accepted:
21
09
2023
medline:
11
10
2023
pubmed:
10
10
2023
entrez:
9
10
2023
Statut:
epublish
Résumé
RNA polymerase (RNAP) is emblematic of complex biological systems that control multiple traits involving trade-offs such as growth versus maintenance. Laboratory evolution has revealed that mutations in RNAP subunits, including RpoB, are frequently selected. However, we lack a systems view of how mutations alter the RNAP molecular functions to promote adaptation. We, therefore, measured the fitness of thousands of mutations within a region of rpoB under multiple conditions and genetic backgrounds, to find that adaptive mutations cluster in two modules. Mutations in one module favor growth over maintenance through a partial loss of an interaction associated with faster elongation. Mutations in the other favor maintenance over growth through a destabilized RNAP-DNA complex. The two molecular handles capture the versatile RNAP-mediated adaptations. Combining both interaction losses simultaneously improved maintenance and growth, challenging the idea that growth-maintenance tradeoff resorts only from limited resources, and revealing how compensatory evolution operates within RNAP.
Identifiants
pubmed: 37813857
doi: 10.1038/s41467-023-41882-7
pii: 10.1038/s41467-023-41882-7
pmc: PMC10562459
doi:
Substances chimiques
DNA-Directed RNA Polymerases
EC 2.7.7.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6319Informations de copyright
© 2023. Springer Nature Limited.
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