Genetic Background and Environment Influence the Effects of Mutations in pykF and Help Reveal Mechanisms Underlying Their Benefit

Resolving the relationship between genotypic and their effects remains a central challenge in the study of adaptation. Although parallel mutations, a signature of adaptation, have been observed a lot in natural and lab-evolved populations, it is unknown if they are equally adaptive, or even if they affect similar biological processes to cause phenotypic changes. Using eight independently occurring mutations in pykF identified from a long-term evolution experiment with Escherichia coli, I found the mutations confer similar benefits in the ancestral background, but variable effects in the background in which they were evolved. Differences in mutation × background interactions were found to be driven by different suites of mutations in each genetic background, rather than by different pykF mutations. Through biochemical and physiological studies with the pykF mutations in the ancestor, I found that although the mutations affect enzymes in a range of different ways, the net effect of these changes is to lead to changes in the same biological pathways, and thus to confer similar fitness effects.

An adaptive mutation may no longer be beneficial if the given genetic background or environment changes. Relatively few studies, however, have examined the combined effect of genetic and environmental context on fitness effects of a mutation. To do this, I measured fitness effect conferred by one pykF mutation in 23 divergent genetic backgrounds and five environments. I found the environment, genetic background, and interactions between them, all significantly affect fitness of the mutation, which makes it harder to predict evolutionary fate of new mutations. Nevertheless, I found that initial fitness of a progenitor strain can be used to predict contribution of a mutation: a mutation will contribute less when added to fitter progenitors.