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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
rpoB variants under multiple conditions and genetic backgrounds, to find
that adaptive mutations cluster in two separate 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.
45 views reported since publication in 2023.