We just posted two new preprints to bioRxiv from our lab's work on how ecological interactions affect mutant fitness. The first is titled "A theoretical framework for how ecological interactions between microbes affect mutant fitness." The distribution of fitness effects (DFE) for spontaneous mutations characterizes both an organism's evolutionary potential as well as its genomic functions. The DFE of a genome depends on the specific environment in which it is measured, and for microbes a major feature of their environment is the presence of interactions with other species, such as competing for or cross-feeding nutrients. Several recent studies have empirically measured how the DFE of one microbial species changes in the presence of interactions with other species. However, the underlying mechanisms by which this happens, and the statistical patterns they are expected to produce, are unknown. Here we classify two types of statistical changes in the DFE: global changes to the DFE, such as to its mean or variance, and idiosyncratic changes in the fitness of individual mutants, summarized by the correlation of mutant fitness between environments. We first show that both types of effects occur in empirically measured DFEs across a wide range of species and interactions; idiosyncratic effects appear to have a maximum limit and constrain the size of global effects. We then show that a minimal model of an ecological interaction (competition for a single resource) is sufficient to generate both types of effects. Finally, we extend this model to arbitrary quantitative traits to reveal two general mechanisms of how interactions alter the DFE: 1) interactions can globally change fitness by altering the community growth rate, and 2) interactions can idiosyncratically change fitness of individual mutants by altering relative selection on different traits affected by those mutations.
The second preprint is titled "Amino acid cross-feeding in E. coli globally and idiosyncratically alters mutant fitness." Cross-feeding between microbes is believed to be common in many natural ecosystems, especially between species that are auxotrophic for essential nutrients such as amino acids. Several recent studies have demonstrated that cross-feeding and other ecological interactions between microbes alter their evolution and the fitness of mutations. However, these studies focused on interactions between different species, where the nature of the interaction is complex due to the large genetic differences between species, making it difficult to directly attribute changes in mutant fitness to a specific interaction. To address this problem, we use a synthetic cross-feeding interaction between isoleucine and methionine auxotrophs of Escherichia coli, two commonly observed auxotrophies in bacterial genomes. Using a library of genome-wide knockout mutants from transposon insertions, we measure the fitness of these mutants in the presence and absence of cross-feeding. We find that cross-feeding either isoleucine or methionine globally shifts mutant fitness to become more beneficial on average by inducing strong positive selection on a few mutants and rescuing strongly deleterious mutants. However, cross-feeding also affects mutants idiosyncratically: the most beneficial mutants under cross-feeding are neutral or deleterious without cross-feeding, and cross-feeding isoleucine affects different genes than cross-feeding methionine does. We discover one spontaneous mutant, with especially dramatic idiosyncratic effects under isoleucine cross-feeding, that achieves this phenotype by becoming a partial threonine auxotroph and reversing its ancestral isoleucine auxotrophy. This work directly demonstrates the statistical patterns and possible mechanisms by which a common ecological interaction between microbes alters their mutant fitness.
