EGR · The role of genetic redundancy in adaptive evolution of efflux pumps

The role of genetic redundancy in adaptive evolution of efflux pumps

This project addresses the broad problem of genetic redundancy and its role in evolution. Genetic redundancy refers to the fact that multiple genes in a genome can carry out similar or identical functions. Because these genes can substitute each other functionally, the loss of some genes often has no apparent effect on biological fitness. Despite this, genetic redundancy is widespread across many organisms, including bacteria, suggesting that having redundant genes is advantageous even for species with relatively small genomes. This raises fundamental questions: why have functionally replaceable genes persisted for long evolutionary time, and is genetic redundancy evolutionarily advantageous? To address these questions, we employed gene editing, deep sequencing, and computational analysis. We focused on genes encoding multidrug resistance efflux pumps. Efflux pumps are membrane proteins that actively export specific chemicals, including antibiotics, out of cells. The efflux of antibiotics is one of the major mechanisms allowing pathogenic bacteria to resist antibiotic exposure and leading to treatment failure. Most pathogenic bacteria have multiple multidrug resistance efflux pumps, representing five protein families with distinct structures and mechanisms yet overlapping activities against antibiotics. This makes efflux pumps a good model to study genetic redundancy.

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