Unit: Molecular Biology of the Gene in Extremophiles
Director: Patrick FORTERRE
The living world is presently divided into three cellular lineages: the Bacteria, the Archaea and the Eucarya. We are interested in the events and mechanisms that lead to the establishment of these three lineages and in the role those viruses have played in that history. We focus our attention on the Archaea. These prokaryotic microorganisms exhibit, at the molecular level, both unique features and a mixture of bacterial and eucaryal features.
Viruses from hyperthermophilic Archaea. (David Prangishvili, Monica Haëring, Alexandra Kessler, Soizick Lucas, Tamara Basta, Ariane Bize, Jean-Marie Clément, Guennadi Sezonov)
Our unit was created in January 2004 and has been operational from October 2004. Our main experimental work is devoted to the study of viruses from hyperthermophilic Archaea of the phylum Crenarchaea. Previous studies in Munich and Regensburg by Wolfram Zillig and David Prangishvili have shown that these viruses exhibit an incredible morphological and genetic diversity, exceeding that of bacterial viruses. In addition, some of them even bear resemblance to human viruses.
We have started to study several viruses recently isolated by David Prangishvili from various strains of Sulfolobales (genera Acidianus and Sulfolobus) that are representatives of several new viral families: the virus SIRV, whose genome exhibits structural similarities with Poxvirus genomes, the virus AFV, that exhibits telomeric-like sequences at the extremities of its linear genome and carries terminal clamps to grasp host pili, the bottle-shaped virus ABV, and finally the virus ATV, that exhibits a spectacular extracellular development stage observed for the first time in any virus.
We will continue to study the molecular and structural characterization of these viruses, focusing in particular on their replication machinery and the determinants of their unique morphologies. Structural studies will be performed in collaboration with various groups (Félix Rey (Gif sur Yvette/Institut Pasteur), Muriel Delepierre (Institut Pasteur), Nicolas Boisset (University Paris-VI) and Dennis Bamford (Helsinki). Another of our objectives is to use some of our viruses to develop new genetic tools for hyperthermophilic Archaea. Finally, we also plan to search for further new viruses by collecting samples in future expeditions in various terrestrial hot springs.
We think that, in order to get a comprehensive picture of the microbial diversity on our planet and of its history, it is important to understand why different types of terrestrial environments and/or different groups of microorganisms have given rise to such a diverse and distinct viral fauna. In addition, hyperthermophilic viruses encode proteins that in most cases have no homologues in the rest of the living world. We suspect that some of these will exhibit unique structural features and have an important biotechnological potential.
Looking for pathogenic Archaea (David Musgrave)
Recently, studies in molecular ecology have revealed the existence of many mesophilic Archaea that thrive in a wide variety of cold or temperate environments, either anaerobic or micro-aerobic. We are looking for such archaea in human tissues, especially in association with pathologies of unknown origin.
Genome evolution, molecular phylogeny and comparative genomics (Simonetta Gribaldo, Guennadi Sezonov, Lars Jermiin)
We use in silico approaches (molecular phylogeny, comparative genomics) to study the evolution of major molecular systems, the mechanisms of genome evolution and to reconstruct deep phylogenies with a focus on the evolutionary history of Archaea. One of our aims is also to identify new fundamental molecular mechanisms which are conserved between cellular lineages.
We have obtained convergent phylogenies of the domain Archaea based on both ribosomal proteins and RNA polymerases (collaboration with Céline Brochier, Marseille). This result shows the existence of a core of genes that have been vertically inherited and are therefore excellent molecular markers to reconstruct the history of Archaea. In the course of this work, we have observed a correlation between the rapid evolutionary rate of the genome of the archaeon Methanopyrus kandleri and the lack of the transcription factor TFS. This suggests a link between the fidelity of transcription and the rate of genome evolution that could be conserved from Bacteria to Humans. We are testing this hypothesis using mutants of the functional analogous proteins in Bacteria.
We plan to perform phylogenetic analyses of proteins with viral and cellular homologues (RNA polymerases, DNA topoisomerases, etc.) in order to test recent hypothesis on the role of viruses in early cellular evolution (origin of DNA and/or origin of the eukaryotic nucleus). In general, we are interested by problems related to the nature of the last universal common ancestor (LUCA) or else by the position of hyperthermophiles in the history of life.
Epistemological and historical studies of the work of Carl Woese (Chloé Terras)
The elaboration of the archaeal concept by Carl Woese has triggered a revolution in our understanding of the living world. One of our PhD students, Chloé Terras, has undertaken an historical study to better understand the origin of this revolution and its impact on the history of biology.
Viruses from hot (>80°C) terrestrial biotopes.
Keywords: Archaea, Virus, Evolution, comparative genomics, Replication, Transcription, Molecular phylogeny