Evolution of a Dominant Natural Isolate of Escherichia coli in the Human Gut over the Course of a Year Suggests a Neutral Evolution with Reduced Effective Population Size

Abstract

In vitro and in vivo evolution experiments on Escherichia coli revealed several principles of bacterial adaptation. However, few data are available in the literature describing the behavior of E. coli in its natural environment. We attempted here to study the evolution in the human gut of a commensal dominant E. coli clone, ED1a belonging to the B2 phylogroup, through a longitudinal genomic study. We sequenced 24 isolates sampled at three different time points within a healthy individual over almost a year. We computed a mutation rate of 6.90 × 10^-7 mutations per base per year of the chromosome for E. coli ED1a in healthy human gut. We observed very limited genomic diversity and could not detect any evidence of selection, in contrast to what is observed in experimental evolution over a similar length of time. We therefore suggest that ED1a, being well adapted to the healthy human gut, evolves mostly neutrally with a low effective population size (N_e of ≈500 to 1,700).IMPORTANCE In this study, we follow the genomic fate of a dominant clone of Escherichia coli in the human gut of a healthy individual over about a year. We could compute a low annual mutation rate that supports low diversity, and we could not retrieve any clear signature of selection. These observations support a neutral evolution of E. coli in the human gut, compatible with a very limited effective population size that deviates drastically with the observations made previously in experimental evolution.

Keywords: ED1a; Escherichia coli; human gut; molecular evolution; mutation rate; neutral evolution; replication rate.

FIG 1

Genomic diversity of E. coli ED1a over almost a year in a healthy human gut. We represented a maximum likelihood unrooted tree relating all isolates sampled over a year reconstructed with the packages ape (55) and phangorn (56) in R software (34). The length of the branches is proportional to the number of mutations separating two samples. The diameters of circles are proportional to the numbers of isolates that are identical. Color codes are as follows: blue, isolates sampled at day 0 (D0); violet, isolates sampled at day 211 (D211); red, isolates sampled at day 315 (D315). The intergenic mutations are represented by two genes separated by a slash. The nonsynonymous and synonymous SNPs are marked by (NS) and (S), respectively. Deletion mutations (12 bp in the putA gene and 3 bp in a repeated region of the cpdA gene) are indicated with a Greek delta (Δ). A stop codon is indicated with an asterisk (*). The mutations occurring on the plasmid are shown in blue.