Microbial evolutionary genomics


Not Chaos like together crush'd and bruis'd,
But as the world, harmoniously confus'd

Alexander Pope, in Windsor Forest

Creativity and organization are often in conflict, both in natural and in social systems. Bacterial genomes do not escape this general rule when creativity is related to the generation of genetic novelty and organisation with the stability of selective arrangements of genetic elements in the chromosome. The availability of genome data has allowed the understanding of many features concerning both chromosome organisational structure and the generation of genetic variability in bacterial populations. Chromosome organisation involves selective features such as the distribution of genes relative to replication, segregation or expression, which may be biased by expression levels, essentiality or function. It also involves the biased distribution of nucleotides and oligonucleotides in the genomes, which may be caused by mutational or selective processes, but has, in any case, an important impact on chromosome structure. Most of our work on the organisation of chromosomes has focused on the study of their replication-related structure.

The replication of the chromosome is among the most essential functions of the bacterial cell and influences many other cellular mechanisms, from gene expression to cell division. Yet, the way it impacts on the bacterial chromosome was not fully acknowledged until complete genomes allowed one to look upon genomes as more than bags of genes. Chromosomal replication includes a set of asymmetric mechanisms, among which a division in a lagging and a leading strand and a gradient between early and late replicating regions. These differences are the causes of many of the organizational features observed in bacterial genomes, both in terms of gene distribution and sequence composition along the chromosome. When asymmetries or gradients increase in some genomes, e.g. due to a different composition of the DNA polymerase, or to a higher growth rate, so do the corresponding biases. As some of the features of the chromosome structure seem to be under strong selection, understanding such biases is important for the understanding of the chromosome organization and adaptation. Inversely, understanding chromosome organization may shed further light on questions relating to replication and cell division.

The mechanistic nature of genotypic variation in bacteria may assume many different routes, such as duplications or deletions of genetic material, horizontal transfer or point mutations. Recombination plays a major role in many of such events, since it is related with phage integration, horizontal transfer, major chromosomal rearrangements, fast adaptation of exposed proteins in pathogens and repair of stalled replication forks. One typically classifies intra-chromosomal recombination into homologous recombination (dependent of RecA), site-specific recombination (dependent on specific recombinases) and illegitimate recombination. The frequency of homologous and illegitimate recombination depends on the similarity between the two copies of a repeat that pair in the recombination process. Therefore intra-chromosomal recombination hotspots can be identified in silico from genome sequences. We have been doing that for several years and recently we have concentrated on the protein structure effects of intragenic duplications.

Intra-genomic recombination mechanisms have a particularly important role in adaptation via gene dosage effects or fast local sequence variation. Yet, they also tend to produce rearrangements in the chromosome, disrupting chromosome organisation. We have shown that this creates an evolutionary conflict between purifying selection for organised features in the bacterial chromosomes and positive selection for repeated elements capable of generating genotypic variability or gene dosage effects. The resulting trade-offs between organisation and genotypic creativity depend on bacterial ecological, genetic and physiological characteristics such as lifestyles, population sizes, recombination mechanisms and growth rates. Hopefully, these studies will allow a better understanding of the differences in terms of genome plasticity found within and between bacterial genomes.

Finally, we have also been working on the uses of comparative genomics in ecology and evolutionary ecology in particular. We study the dynamics and effects of mobile genetic elements, such as phages, plasmids and transposable elements. We have been doing this work using molecular, evolutionary and ecological perspectives. Most frequently it's when we put together the different perspectives that we obtain the mos interesting results. This is because the availability of large-scale datasets in terms of genome sequence, metabolism, expression and phylogeny allow tackling questions that up to now remained illusive.