Recombination and Epistasis at the Genome level, extant, molecular bases and implication on clone emergence in Escherichia coli – EcoRecEp

The spread of antibiotic resistance has clearly illustrated the need for an evolutionary approach to study infectious diseases. With the advent of genomics, molecular epidemiology clusters strains according to their genetic characteristics and looks for associations between these groups and variable phenotypes ranging from the hosts where they are isolated to the pathologies they cause. However, the evolutionary processes behind this intraspecific diversification are not clear, especially since genomics revealed important gene fluxes. Within a species such as Escherichia coli, which kills nearly one million people a year through various pathologies, numerous clonal or phylogroup specificities are observed despite important genetic exchanges. These exchanges, by allowing any strain to benefit from the advantage associated with a gene received by transfer, should strongly limit the associations observed between phylogeny and specificities. The extreme case being antibiotic resistance carried by plasmids that are easily transmitted and yet remain strongly associated with certain groups of strains such as the epidemic E. coli sequence type ST131.
To explain the emergence and successes of diverse clones including some with antibiotic resistance, genetic exchanges within the species must be asymmetric due to mechanistic barriers limiting the integration of genetic material or selective barriers due to epistatic interactions between various parts of the genome that are disrupted during genetic exchanges. While the study of these processes was until recently confined to a theoretical approach, we propose here a unique approach combining experiments and sequence analysis. The ability to reproduce high frequency genetic exchanges in the laboratory coupled with the analysis of tens of thousands of sequenced genomes and the access to very well characterised natural isolates will allow us to take a new quantitative look at the emergence of bacterial clones within E. coli.