|Genetics of Bacterial Genomes - CNRS URA2171|
|HEAD||Antoine Danchin / email@example.com|
Dr. Anne-Marie Gilles / Evelyne Turlin / Emma Brito-Fravallo / Dr. Olga Soutourina / Isabelle Martin-Verstraete
Dr. Catherine Tanous / Dr Elise Haudecoeur / Gaëlle André / Marie-Françoise Hullo / Evelyne Krin
Emmanuelle Courtois / Dr Undine Mechold / Elie Toledano / Dr. Agnieszka Sekowska / Andrew Martens
Tingzhang Wang / Dr. Sandra Cescau / Dr. Jean-Baptiste Masson / Chantal Sylvain
Dr. Philippe Glaser / Dr. Isabelle Rosinski-Chupin / Elizabeth Couvé / Violette Da Cunha
John von Neumann showed that if a computer had to make a computer, it needed an image of the machine within, passed along from generation to generation. Our research pushes the genetic program metaphor to its limits: is it possible to see the cell as a living computer ? What are the implications in terms of the concrete biological objects that make it run? Accidents of replication modify genes, make them disappear or move. One observes that they rapidly distribute more or less randomly. Yet, is their order random? Where are located the gene products, are they found everywhere? We explored this conjecture with experiments meant to uncover some of the physico-chemical constraints organising the cell. To this aim, experimental work is combined with work in silico, conceptual investigations serving as references and predictions for experiments.
Gene “persistence”. As a start point, we analysed how DNA and genes are handled by the various machineries in bacteria, explored the diversity of the corresponding processes and looked for common features. Bacterial genome diversity uncovers the nature of processes imbedded in the genetic programs, resulting both in their universal nature and diversity. The core of our approach explores the relationships between biological objects, trying to relate the architecture of the genome to that of the cell. Genes that persist in bacterial genomes cluster together. We showed that being persistent provides enough power for creating clusters in genomes that are permanently witnessing fluxes of genes going in and out.
Babies are born very young! Analysis of gene persistence identified, contrary to expectation, too many genes (approximately 500). Half of those are essential for life in the laboratory. The other half comprises genes coding for functions that solve chemical mutual incompatibilities between reactive molecules, and functions that code for energy-dependent degradative processes. We related this latter category to a general information theory which shows that accumulation of information requires using energy to make room while preventing >degradation of functional entities. This underlies a completely novel view of the process of natural selection. This view accounts for the fact that aged organisms have a young progeny, using to this aim a process that accumulates information, in a non-oriented way, in passing. We are analysing experimentally the process of adaptive mutation to identify the functions necessary for this accumulation, as well as the associated energy supply. We conjecture, as the corresponding genes are among the non-essential persistent genes, that the mineral polyphosphates may be an ultimate, stable, energy source.
Sulfur metabolism: anabolism, salvage and control of "nanoRNA" degradation. We also focused on reactivity of the sulfur atom as a further integrative process. Many new features of sulfur metabolism were discovered and a side-product of its assimilation, 3’5’AMP, is a regulator of very small RNA degradation, in a pathway that extends from Bacteria to Humans. This has interesting consequences in terms of RNA metabolism, of prime importance for genetic and epigenetic heredity. This experimental work validates the observation in silico that persistent genes keep being organized in bacterial genomes along a pattern that is reminiscent of a scenario of the origin of life beginning with surface metabolism, making the « paleome » which opposed to genes allowing life in context, making the « cenome ».
Keywords: biologie synthétique / origine de la vie / sélection naturelle / métabolisme du soufre / bactéries entomopathogènes / nucléotides / génomique comparative / synthetic biology / origin of life / natural selection / sulfur metabolism / insect pathogens / nucleotides / comparative genomics
G Fang, EPC Rocha, A Danchin How essential are non-essential genes? Mol Biol Evol (2005) 22:2147-2156
C Médigue, E Krin, G Pascal, V Barbe, A Bernsel, PN Bertin, F Cheung, S Cruveiller, S D'Amico, A Duilio, G Fang, G Feller, C Ho, S Mangenot, G Marino, J Nilsson, E Parrilli, EPC Rocha, Z Rouy, A Sekowska, ML Tutino, D Vallenet, G von Heijne, A Danchin. Coping with cold: the genome of the versatile marine Antarctica bacterium Pseudoalteromonas haloplanktisTAC125Genome Res (2005)15: 1325-1335
MF Hullo, S Auger, O Soutourina, O, Barzu, M Yvon, A Danchin, I Martin-Verstraete. The conversion of methionine to cysteine in Bacillus subtilis and its regulation J Bacteriol(2007) 189: 187-197
A Danchin, G Fang, S Noria. The extant core bacterial proteome is an archive of the origin of life Proteomics(2007) 7:875-889
A Danchin Natural selection and immortality Biogerontology(2008) Aug 22. [Epub ahead of print]
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