Journal article

Collateral fitness effects of mutations

Jacob D Mehlhoff, Frank W Stearns, Dahlia Rohm, Buheng Wang, Erh-Yeh Tsou, Nisita Dutta, Meng-Hsuan Hsiao, Courtney E Gonzalez, Alan F Rubin, Marc Ostermeier

Proceedings of the National Academy of Sciences | NATL ACAD SCIENCES | Published : 2020

Abstract

The distribution of fitness effects of mutation plays a central role in constraining protein evolution. The underlying mechanisms by which mutations lead to fitness effects are typically attributed to changes in protein specific activity or abundance. Here, we reveal the importance of a mutation's collateral fitness effects, which we define as effects that do not derive from changes in the protein's ability to perform its physiological function. We comprehensively measured the collateral fitness effects of missense mutations in the Escherichia coli TEM-1 β-lactamase antibiotic resistance gene using growth competition experiments in the absence of antibiotic. At least 42% of missense mutation..

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University of Melbourne Researchers

Grants

Awarded by National Science Foundation


Awarded by Australian National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

We thank Michael Stiffler for providing the sequencing count data from which we determined the primary fitness effects and Christian Kaiser, Dan Tawfik, and Wayne Patrick for comments on a draft version of the manuscript. This research was supported by National Science Foundation Grants DEB-1353143 and MCB-1817646 to M.O. A.F.R benefited from an Australian National Health and Medical Research Council (NHMRC) Program Grant (1054618). The research benefited by support from the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support.