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

par Choudhury, Alaksh;Gachet, Benoit;Dixit, Zoya;Faure, Roland ;Gill, Ryan R.T.;Tenaillon, Olivier
Référence Nature communications, 14, 1, 6319
Publication Publié, 2023-12

Article révisé par les pairs

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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.