The Logic of Change: Contextual Adaptation of a Mobile Gene

Abstract

Understanding how genotypes map to fitness is fundamental to the description and prediction of adaptive evolution. Through differential reproductive fitness of heritable variation, populations enhance survival and reproduction within the selective environment. In this dissertation, I employ experimental evolution of cefotaxime resistance in the plasmid-encoded blaTEM with selection occurring in two bacterial species that host this gene. I measure resistance phenotype during the evolution experiment and utilize monoculture barcoded fitness assays to evaluate the competitive ability of numerous plasmid genotypes hosted by the same species in a range of antibiotic environments. I introduce the concept of an adaptive window to delineate the region of concentration space where each sampled mutation would be selectively accessible in each species. We observe that resistance effects of mutations often correlate between species, but the window of selective accessibility is shifted between species due to differences in intrinsic resistance level. In Chapter 2, I perform side-by-side monoculture and coculture barcoded fitness assays to evaluate the competitive ability of plasmid-host pairings across distinct host communities. We observe that both plasmid genotypic fitness and the fitness effect of mutations can depend strongly on host community structure. Together, these chapters demonstrate that the ecology and evolution of mobile genetic elements can be shaped by host genomic and host community contexts. More generally, this dissertation highlights the dynamic nature of the genotype-to-fitness mapping which is modulated by contextual factors ranging from within the gene, cell, or ecosystem.