Blanc SVSE 3 - Sciences de la vie, de la santé et des écosystèmes : Microbiologie, immunologie, infectiosité

Bacteriophage genome dynamics – DYNAMOPHAGE

bacteriophage genomes dynamics

Because phages are massively present in almost every ecosystem where they are searched for, and contribute greatly to the equilibrium of bacterial species encountered in these ecosystems , the scientific community is now aware that these entities, and their dynamics, need be better understood. The present proposal will investigate the dynamics of bacteriophage genomes with a combination of experimental and predictive approaches.

Measuring the impact of recombination on phage genomes evolution

Our goal is to focus on the special characteristics of phage-encoded recombination functions, to develop new methods for the prediction of function of phage genes, and to unveil important and new mechanisms of gene acquisition that will help understanding the evolution of phages, and also shed light on the evolution bacteria, in particular those hosting bacteriophages.

Bacteriophage genomes evolution being faster than that of bacteria, it is often difficult to detect traces of homology between phage genes having the same function. We develop a tool allowing to detect distant homology between genes of known and unknown function, and hence improve phage genome annotations. We also measure the efficiency of genome evolution by homologous recombination among bacteriophages and bacteria.

We have built an interface allowing to visualize the genetic context around genes of various bacteriophages suspected to belong to the same ancestral family, but with a weak signal of homology. When the context is conserved, we conclude that the functional prediction has a good likelihood (see figure 1).
The molecular analysis of homologous recombination has lead us to recognize that phages have a distinct mode of recombination, more efficient and less accurate than bacteria.

We now want to tackle the mechanism through which phage evolve by acquiring new genes, at the moelcular level, and by a comparative genomics approach.

international conference
Viruses of microbes, Bruxelles, Juillet 2012
Marianne de Paepe « Horizontal transfer mediated by bacteriophages in the mouse gut »

National conference
Colloque SFM, Institut Pasteur, Décembre 2012 <

Bacteriophages (or phages) are ubiquitous, and impact greatly the bacterial component of a given ecosystem. In particular, temperate phages, when hosted in bacteria, sometimes express small but critical genes, the morons, that contribute to bacterial fitness, and make them ‘welcome’ by their host. The way morons are acquired is unknown, but our previous studies on the particularities of phage-encoded recombinases suggest that the relaxed fidelity of homologous recombination in phages may favour gene shuffling and thereby, the production of morons.

The three teams defending this proposal want to combine their skills to further understand the dynamics of bacteriophage genomes, combining and alternating experimental and predictive approaches. Two of the teams have already initiated collaboration on this topic, and discovered three large and previously unsuspected families of phage recombinases.

Starting from this observation, the DYNAMOPHAGE project will conduct an in depth experimental characterisation of a representative of each of the three recombinase families, to inquire whether the relaxed fidelity is a general property of phage recombinases. A second axis of the project is based on the detailed bio-informatics analysis of phage-encoded morons, which is expected to give hints at the way these genes were acquired. A third axis, more ambitious, aims at extending the research of the function of all unknown genes in bacteriophages using a combination of distant homology searches and gene context analyses. Results will be interfaced the publicly available Aclame database dedicated to phages. Additional recombinase super-families, or co-factors for the recombinases, may be detected this way, and added to the experimental characterisation axis of the project. The Aclame database will also be extended to archaeal and eukaryotic viruses. Finally, one of the three super-families of phage recombinases contain some full size RecA-like members, but mostly truncated versions of RecA. The last facet of the project will address the raison d’être of this missing, C-terminal domain. For this, a temperate phage containing a full size recA gene instead of its own recombinase will be constructed. This hybrid will be propagated for several thousand generations in the laboratory, in the hope to see the recA gene evolve.

Beyond the goal of studying the dynamics of phage genomes, this proposal has a clear ambition to provide to the scientific community working on viruses a high quality integrated database facilitating gene annotations, which is a renowned challenge for bacteriophages.

Project coordinator

Madame Marie-Agnès PETIT (INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE JOUY-EN-JOSAS) – marie-agnes.petit@jouy.inra.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INRA INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE JOUY-EN-JOSAS
SB2SM / iBiTecS / CEA COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES - CENTRE D'ETUDES NUCLEAIRES SACLAY

Help of the ANR 320,000 euros
Beginning and duration of the scientific project: - 48 Months

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