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Olivier Tenaillon

Publications and source records attributed to Olivier Tenaillon.

3 recordsLinked to original sources

Tempo and mode of genome evolution in a 50,000-generation experiment

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 50,0 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.

Evolutionary Biology

Coevolutionary landscape inference and the context-dependence of mutations in beta-lactamase TEM-1

The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared to recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared to approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20 from the mutated site, reaching thus far beyond residues in direct physical contact.

Bioinformatics

First-step Mutations during Adaptation to Thermal Stress Shift the Expression of Thousands of Genes Back toward the Pre-stressed State

The temporal change of phenotypes during the adaptive process remain largely unexplored, as do the genetic changes that affect these phenotypic changes. Here we focused on three mutations that rose to high frequency in the early stages of adaptation within 12 Escherichia coli populations subjected to thermal stress (42{degrees}C). All of the mutations were in the rpoB gene, which encodes the RNA polymerase beta subunit. For each mutation, we measured the growth curves and gene expression (mRNAseq) of clones at 42{degrees}C. We also compared growth and gene expression to their ancestor under unstressed (37{degrees}C) and stressed conditions (42{degrees}C). Each of the three mutations changed the expression of hundreds of genes and conferred large fitness advantages, apparently through the restoration of global gene expression from the stressed towards the pre-stressed state. Finally, we compared the phenotypic characteristics of one mutant, I572L, to two high-temperature adapted clones that have this mutation plus additional background mutations. The background mutations increased fitness, but they did not substantially change gene expression. We conclude that early mutations in a global transcriptional regulator cause extensive changes in gene expression, many of which are likely under positive selection for their effect in restoring the pre-stress physiology.

Evolutionary Biology