Escherichia coli

The sequence of hundreds of bacterial genomes uncovered the extraordinary diversity and plasticity of metabolic and regulatory networks. However, the dynamics of evolution of such a wide range of functions, and especially the link between genomic modifications, diversity and overall performance of a living organism remains a challenging yet fascinating task.

For most microbiologists, “mechanism” refers to the biochemical or regulatory interactions among genes, proteins and metabolites in a cell. All these interactions have however to be related to fitness, the measure of the reproductive ability of a genotype which is the ultimate parameter of ecological success.

Dynamics of entire genomes is one key of fitness changes, ultimately driving the interactions among genotypes and between genotypes and their environment. By linking changes in genomes to changes in fitness, it is possible to investigate how natural selection is able to re-shape and improve entire genomes, and which functions are more plastic over evolutionary time. Using such an evolutionary perspective is fully complementary to most “Systems Biology “ approaches, which try to understand the global functioning of an organism by the precise analysis of a reference clone and therefore provide a static description of metabolic or regulatory networks. Using an evolutionary perspective is however difficult mainly because the relevant adaptive events that allowed the emergence of the present genomic structure of the organism occurred some unknown time in the past, in unknown conditions, with unknown genomic constraints. To overcome these limitations, we can reproduce evolution in controlled conditions in the laboratory.

In this project, we will use the longest-running evolution experiment, where an ancestral cell of Escherichia coli has been used to propagate twelve populations in a defined environment for 40,000 generations. The evolutionary dynamics of genomes will be investigated by performing Solexa-sequencing of genomes from 135 evolved clones sampled from the different populations at each of ten different time points during evolution.

Among many questions that will be addressed, this project will enable us to understand the successive genetic events leading to the increased performance of bacteria in their environment. Rigorous genetic and functional phenotypic analyses will be combined to dissect the complete adaptive diversification paths that will be uncovered in key populations. We will study how adaptive mutation appearance is constrained by the presence of other mutations and how they affect the metabolic or regulatory networks. We will therefore address for the first time how evolvable are genomic features and what are the molecular bases of such evolvability.

All these populations have been developed by Richard Lenski (Michigan State University), and this project will involve a strong collaboration.

Contact: Julie Poulain (Genoscope) - Dominique Schneider (Université Joseph Fourier) - Olivier Tenaillon (Faculté de Médecine Xavier Bichat)