Tenaillon, O. | Search bioRxiv

bioRxiv2018

The molecular basis of genetic interaction diversity in a metabolic pathway

Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by the dependence of their effects on the genetic background and environment. Even when molecular interactions between genes are known, it is unclear how these translate to organism-level interactions between alleles. We therefore characterized the interplay of genetic and environmental dependencies in determining fitness by quantifying ~4,000 fitness interactions between expression variants of two metabolic genes, in different environments. We detect a remarkable variety of environment-dependent interactions, and demonstrate they can be quantitatively explained by a mechanistic model accounting for catabolic flux, metabolite toxicity and expression costs. Complex fitness interactions between mutations can therefore be predicted simply from their simultaneous impact on a few connected molecular phenotypes.

genetics↗

bioRxiv2016

Accumulation of deleterious mutations during bacterial range expansions

Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present 3-4 times fewer mutations. Estimation of the distribution of fitness effect (DFE) under a spatially explicit model reveals a mean negative effect for new mutations (-0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, we show that the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines remained unchanged. Our results thus suggest that successful expanding species are affected by deleterious mutations that accumulate during the expansion process, leading to a drastic impairment of their evolutionary potential.

evolutionary biology↗