Stearns, F. W. | Search bioRxiv

bioRxiv2023

Scaling the fitness effects of mutations with respect to differentially adapted Arabidopsis thaliana accessions under natural conditions

Mutations are the ultimate source of genetic variation for natural selection to act upon. A major question in evolutionary biology is the extent to which new mutations can generate genetic variation under natural conditions to permit adaptive evolution over ecological time scales. Here we collected fitness data for chemically induced (ethylmethane sulfonate, EMS) mutant lines descended from two Arabidopsis thaliana ecotypes that show differential adaptation to the local environment of our common garden plot. Using a novel nonparametric Bayesian statistical approach, we found that both ecotypes accumulated substantial proportions of beneficial mutations. The poorly adapted ecotype showed higher variance in the fitness effect of mutations than the well-adapted ecotype. Furthermore, we predict that it takes less than 4000 generations for the fitness space of the two ecotypes to overlap through mutation accumulation, and that a single founder, through mutation accumulation, is able to achieve the species-wide genetic variation in less than 10,000 generations. Our results provide evidence for relatively rapid local adaptation of Arabidopsis thaliana in natural conditions through new mutations, as well as the utility of nonparametric Bayesian method for modeling the distribution of fitness effects for field-collected data.

evolutionary biology↗

bioRxiv2019

Collateral fitness effects of mutations

The distribution of fitness effects (DFE) 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 mutations collateral fitness effects, which we define as effects that do not derive from changes in the proteins ability to perform its physiological function. We comprehensively measured the collateral fitness effects of missense mutations in the E. coli TEM-1 {beta}-lactamase antibiotic resistance gene using growth competition experiments in the absence of antibiotic. At least 42% of missense mutations in TEM-1 were deleterious, indicating that for some proteins, collateral fitness effects occur as frequently as effects on protein activity and abundance. Deleterious mutations caused improper post-translational processing, incorrect disulfide-bond formation, protein aggregation, changes in gene expression, and pleiotropic effects on cell phenotype. Deleterious collateral fitness effects occurred more frequently in TEM-1 than deleterious effects on antibiotic resistance in environments with low concentrations of the antibiotic. The surprising prevalence of deleterious collateral fitness effects suggests they may play a role in constraining protein evolution, particularly for highly-expressed proteins, for proteins under intermittent selection for their physiological function, and for proteins whose contribution to fitness is buffered against mutations with deleterious effects on protein activity and protein abundance. Significance StatementMutations provide the source of genetic variability upon which evolution acts. Deleterious protein mutations are commonly thought of in terms of how they compromise the proteins ability to perform its physiological function. However, mutations might also be deleterious if they cause negative effects on one of the countless other cellular processes. The frequency and magnitude of such collateral fitness effects is unknown. Our systematic study of mutations in a bacterial protein finds widespread collateral fitness effects that were associated with protein aggregation, improper protein processing, incomplete protein transport across membranes, incorrect disulfide-bond formation, induction of stress-response pathways, and unexpected changes in cell properties. Our results suggest that deleterious collateral fitness effects may be an important constraint on protein evolution.

evolutionary biology↗