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.
The primary habitat of Escherichia coli is the vertebrate gut, where it is the predominant aerobic organism, living in symbiosis with its host. Despite the occurrence of recombination events, the population structure is predominantly clonal, allowing the delineation of major phylogenetic groups. The genetic structure of commensal E. coli is shaped by multiple host and environmental factors, and the determinants involved in the virulence of the bacteria may in fact reflect adaptation to commensal habitats. A better characterization of the commensal niche is necessary to understand how a useful commensal can become a harmful pathogen. In this Review we describe the population structure of commensal E. coli, the factors involved in the spread of different strains, how the bacteria can adapt to different niches and how a commensal lifestyle can evolve into a pathogenic one.
To estimate the number and diversity of beneficial mutations, we experimentally evolved 115 populations of Escherichia coli to 42.2°C for 2000 generations and sequenced one genome from each population. We identified 1331 total mutations, affecting more than 600 different sites. Few mutations were shared among replicates, but a strong pattern of convergence emerged at the level of genes, operons, and functional complexes. Our experiment uncovered a set of primary functional targets of high temperature, but we estimate that many other beneficial mutations could contribute to similar adaptive outcomes. We inferred the pervasive presence of epistasis among beneficial mutations, which shaped adaptive trajectories into at least two distinct pathways involving mutations either in the RNA polymerase complex or the termination factor rho.
The evolutionary significance of stress-induced mutagenesis was evaluated by studying mutagenesis in aging colonies (MAC) of Escherichia coli natural isolates. A large fraction of isolates exhibited a strong MAC, and the high MAC variability reflected the diversity of selective pressures in ecological niches. MAC depends on starvation, oxygen, and RpoS and adenosine 3',5'-monophosphate regulons; thus it may be a by-product of genetic strategies for improving survival under stress. MAC could also be selected through beneficial mutations that it generates, as shown by computer modeling and the patterns of stress-inducible and constitutive mutagenesis. We suggest that irrespective of the causes of their emergence, stress-induced mutations participate in adaptive evolution.
We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.
Adaptation by natural selection depends on the rates, effects, and interactions of many mutations, making it difficult to determine what proportion of mutations in an evolving lineage are beneficial. We analysed 264 complete genomes from 12 Escherichia coli populations to characterize their dynamics over 50,000 generations. The populations that retained the ancestral mutation rate support a model where most fixed mutations are beneficial, the fraction of beneficial mutations declines as fitness rises, and neutral mutations accumulate at a constant rate. We also compared these populations to mutation-accumulation lines evolved under a bottlenecking regime that minimizes selection. Nonsynonymous mutations, intergenic mutations, insertions, and deletions are overrepresented in the long-term populations, further supporting the inference that most mutations that reached high frequency were favoured by selection. These results illuminate the shifting balance of forces that govern genome evolution in populations adapting to a new environment.
*These authors contributed equally to this work.Adaptation depends on the rates, effects, and interactions of many mutations. We analyzed 264 genomes from 12 Escherichia coli populations to characterize their dynamics over 50,000 generations. The trajectories for genome evolution in populations that retained the ancestral mutation rate fit a model where most fixed mutations are beneficial, the fraction of beneficial mutations declines as fitness rises, and neutral mutations accumulate at a constant rate. We also compared these populations to lines evolved under a mutation--accumulation regime that minimizes selection. Nonsynonymous mutations, intergenic mutations, insertions, and deletions are overrepresented in the long--term populations, supporting the inference that most fixed mutations are favored by selection. These results illuminate the shifting balance of forces that govern genome evolution in populations adapting to a new environment.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
Mutations are the ultimate source of heritable variation for evolution. Understanding how mutation rates themselves evolve is thus essential for quantitatively understanding many evolutionary processes. According to theory, mutation rates should be minimized for well-adapted populations living in stable environments, whereas hypermutators may evolve if conditions change. However, the long-term fate of hypermutators is unknown. Using a phylogenomic approach, we found that an adapting Escherichia coli population that first evolved a mutT hypermutator phenotype was later invaded by two independent lineages with mutY mutations that reduced genome-wide mutation rates. Applying neutral theory to synonymous substitutions, we dated the emergence of these mutations and inferred that the mutT mutation increased the point-mutation rate by ∼150-fold, whereas the mutY mutations reduced the rate by ∼40-60%, with a corresponding decrease in the genetic load. Thus, the long-term fate of the hypermutators was governed by the selective advantage arising from a reduced mutation rate as the potential for further adaptation declined. experimental evolution | genomics | mutators | phylogenomics M utations are the ultimate source of heritable variation for evolution. Therefore, understanding how selection can change mutation rates is crucial for quantitatively describing evolutionary processes (1). More mutations are deleterious than beneficial (2), and organisms from bacteria to eukaryotes encode proofreading and repair enzymes that reduce mutation rates (3). If selection for beneficial mutations is weak relative to selection against deleterious mutations, then the rate of adaptation in asexual populations is maximized at some intermediate mutation rate (4). However, when populations encounter new environments, selection for beneficial mutations can be strong (5), and much higher mutation rates may evolve. Indeed, surveys of laboratory populations of microbes (6-10), clinical isolates of bacterial pathogens (11,12), and some types of eukaryotic tumors (13) have revealed a surprisingly high proportion of lineages that have evolved genetic defects in repair pathways. These hypermutators often have 10-to 100-fold increased mutation rates, and such elevated mutation rates can accelerate the progression of chronic diseases and the evolution of resistance to therapeutic agents.Hypermutable mutants can become established in asexual populations while they adapt to changed environments owing to their higher per capita probability of discovering rare beneficial mutations compared with nonmutators (14-18). Although hypermutable genotypes should produce beneficial mutations at a higher rate than their less mutable counterparts, they do not necessarily increase the rate of adaptation to a corresponding, or even measurable, degree. In large asexual populations, the waiting time for new beneficial mutations to occur may be short relative to the time required for a mutant to increase from one individual to fixation in the population, assuming the be...
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