The budding yeast, Saccharomyces cerevisiae, is the workhorse of the brewing industry. Brewers have domesticated a vast array of different strains with traits that complement the beers they wish to br...

Most mutations are neutral or deleterious, and mutator alleles that increase the mutation rate of an organism are considered rare and short-lived. Here, we report a genomic signature consistent with t...

In simple microbial populations, the fitness effects of most selected mutations are generally taken to be constant, independent of genotype frequency. This assumption underpins predictions about evolutionary dynamics, epistatic interactions, and the maintenance of genetic diversity in populations. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli Long-Term Evolution Experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in approximately 80\% of strain pairs tested. Most competitions exhibit negative frequency-dependence, where fitness advantages decline as mutant frequency increases. Furthermore, we demonstrate that the strength of frequency-dependence is predictable from invasion fitness measurements, with invasion fitness explaining approximately half of the biological variation in frequency-dependent slopes. Additionally, we observe violations of fitness transitivity in several strain combinations, indicating that competitive relationships cannot always be predicted from fitness relative to a single reference strain alone. Through high-resolution measurements of within-growth cycle dynamics, we show that simple resource competition explains a substantial portion of the frequency-dependence: when faster-growing genotypes dominate populations, they deplete shared resources more rapidly, reducing the time available for fitness differences to accumulate. Our results demonstrate that even in a simple model system designed to minimize ecological complexity, subtle ecological interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary dynamics. ### Competing Interest Statement The authors have declared no competing interest.

A Bit About Us: We are Arcadia Science, an evolutionary biology company founded and led by scientists. Our mission is to turn natural innovations into real-world solutions by developing systematic, an...

Are you ready to lead groundbreaking research in Genome Biology? Join us at EMBL! We are seeking a motivated scientist to lead an independent research group addressing exciting and original biological...

Join us! Our lab is based at the University of California, Berkeley, embedded in the vibrant and multicultural San Francisco Bay Area, surrounded by astonishing nature!

In this Review, Ascensao and Desai discuss how methodological advances in genotype and phenotype manipulation are transforming experimental evolution approaches and providing new insights into the und...

University of California, Irvine is hiring. Apply now!

Postdoctoral positions in structural biology of macromolecular complexes are available in the laboratory of Dr. Eva Kowalinski at the EMBL Grenoble, France. We are looking for highly motivated and amb...