Deep mutational scanning reveals the molecular determinants of RNA polymerase-mediated adaptation and tradeoffs

Autor: Alaksh Choudhury, Benoit Gachet, Zoya Dixit, Roland Faure, Ryan T. Gill, Olivier Tenaillon
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-41882-7
Popis: Abstract 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.
Databáze: Directory of Open Access Journals