Harnessing Rapid Evolution to Advance the Synthetic Biology Toolbox for Wild Microbes

The community structure of any microbial ecosystem results from a complex set of interactions between cells, viruses, and molecules, and these interactions are a result of constant, often rapid evolution. In wild microbial genomes, localized hypervariation (mediated by viruses and horizontal/lateral gene transfer) can generate massive genetic diversity, offering selective advantages by optimizing a variety of cellular and viral functions. Organisms in several environments (e.g., marine, soil, groundwater), and spanning most of the microbial tree of life, have recently been identified by our team with a capacity for rapid protein evolution. We have observed highly precise mutation occurring naturally in bacterial, archaeal, and viral genomes, directed by a class of retroelements that can select particular regions of target genes for rewriting. Moreover, our research has found that organisms are capable of recruiting these genetic tools to hypermutate a variety of genes on chromosomes and plasmids. Taken together, these recent discoveries constitute a natural system, which serves as a modular tool for targeted protein, pathway, and chassis engineering for any organism of interest. Such a toolset would be invaluable for the transformation and evolution of non-model microbes, for which no such tools exist.