Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths

The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the ∼18,000 families of orthologous genes, we found ∼2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome.
Author Summary Although abundant knowledge has been accumulated regarding the E. coli laboratory strain K-12, little is known about the evolutionary trajectories that have driven the high diversity observed among natural isolates of the species, which encompass both commensal and highly virulent intestinal and extraintestinal pathogenic strains. We have annotated or re-annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Although recombination rates are much higher than mutation rates, we were able to reconstruct a robust phylogeny based on the ∼2,000 genes common to all strains. Based on this phylogeny, we established the evolutionary scenario of gains and losses of thousands of specific genes, identifying functional classes under opposite selection pressures. This genome flux is confined to very few positions in the chromosome, which are the same for every genome. Notably, we identified few or no extraintestinal virulence-specific genes. We also defined a long-scale structure of recombination in the genome with lower recombination rates at the terminus of replication. These findings demonstrate that, despite a very high gene flow, genes can co-exist in an organised genome.