Evolutionary innovation using EDGE, a system for localized elevated mutagenesis

Abstract

Mutations arising across the whole genome can hinder the emergence of evolutionary innovation required for adaptation because many mutations are deleterious. This trade-off is overcome by elevated mutagenesis to localized loci. Examples include phase variation and diversity-generating retroelements. However, these mechanisms are rare in nature; and all have narrow mutational spectra limiting evolutionary innovation. Here, we engineer a platform of Experimental Designed Genic Evolution (EDGE) to study the potential for evolutionary novelty at a single locus. Experimental evolution with EDGE shows that bacterial resistance to a novel antibiotic readily evolves, provided that elevated mutagenesis is focused on a relevant gene. A model is proposed to account for the cost and benefit of such single loci to adaptation in a changing environment and explains their high mutation rates, limited innovation, and the rarity of localized mutagenesis in nature. Overall, our results suggest that localized mutation systems can facilitate continuing adaptive evolution without necessarily restricting the spectrum of mutations. EDGE has utility in dissecting the complex process of adaptation with its localized, efficient evolution.

Analysis of lineage-specific protein family variability in prokaryotes combined with evolutionary reconstructions

“…High protein variability and evolutionary fluidity appear to be often associated with the protein's role in various biological conflict scenarios [15,16], sometimes serving as a hallmark for the discovery of novel defense and offence systems in prokaryotes [17,18]. Discovery of multiple diversity-generating mechanisms [19][20][21], which target gene regions that need to adapt particularly rapidly, underscore the importance of this phenomenon.…”

Plasmid hypermutation using a targeted artificial DNA replisome

“…Previous in vivo mutagenesis tools lack one or more of these features (table S1). Some of these tools repurpose complex natural systems (3)(4)(5)(6)(7)(8)(9)(10)(11)(12), whose intrinsic complexity limits functions of the tools. The requirement of coupling the target function to the expression of phage protein (7) limits the traits that can be evolved, and the inability to switch mutagenesis on/off (4,6,7,9) complicates identification of beneficial mutations.…”