Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations.

ABSTRACT: Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, many resistance mutations have a substantial fitness cost and are subject to purifying selection. How emerging resistant lineages may escape purifying selection via subsequent compensatory mutations is still unclear due to the difficulty of tracking such evolutionary rescue dynamics in space and time. Here, we introduce a system of fluorescence-coupled synthetic mutations to show that the probability of evolutionary rescue, and the resulting long-term persistence of drug resistant mutant lineages, is dramatically increased in dense microbial populations. By tracking the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies we un

SUBMITTER: Aif S 

PROVIDER: S-EPMC9789051 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature