Bernard Dujon is a French geneticist, born on August 8, 1947, in Meudon (Hauts-de-Seine). He is Professor Emeritus at Sorbonne University and the Institut Pasteur since 2015. He is a member of the French Academy of sciences.

Early life and education Bernard Dujon grew up as a teenager in the Paris suburban area and went to school at Maisons-Lafitte, where his parents settled in 1958. He became interested in biology very early and at the age of eleven started collecting biological material from his natural environment, plants, fossils, insects, shells, etc. He became in 1965 a laureate of the Concours Général, a nation-wide yearly contest, at the same time he was obtaining his baccalauréat. He started a degree of biology at the Faculté des Sciences de Paris the same year. He graduated in the top 1% of students and was offered the opportunity to compete for an oral exam at Ecole Normale Supérieure (ENS rue d'Ulm), was ranked first and admitted there the following year (1966). He therefore became a normalien at the early age of 19, when most of the students attracted by this career are still preparing in specialized schools for this written and oral competition. There, he attended lectures at the Faculté de Sciences for two years, before choosing Genetics as a specialization during his third year. After a master's degree in Genetics from Pierre and Marie Curie University, Paris (1968), he received a Diploma of Advanced Studies (DEA) in Advanced Genetics (1969). Subsequently, instead of preparing the agrégation, that would have ensured a permanent position in the education system, he decided to follow doctorate studies under the supervision of Piotr Slonimski, a Polish-French geneticist, at the CNRS campus of Gif-sur-Yvette, in the southern parisian suburban area. At the same time, he was recruited as a junior scientist by the CNRS (1970), allowing him to complete his PhD thesis, while earning a salary to support his family. He eventually obtained a Doctorate in Natural Sciences, specializing in Genetics, in 1976, from the Pierre and Marie Curie University.

Functions in science and education He was a trainee, then attaché, chargé and research master at the CNRS from 1970 to 1983, then a Professor at the Pierre and Marie Curie University from 1983 to 2015, at the same time part-time assistant professor at the Ecole Polytechnique (1984-1988). From 1989 to 1992 he was Head of Laboratory at the Institut Pasteur, then Professor from 1993 to 2015. He was the head of the Unité de Génétique Moléculaire des Levures from 1989 to his retirement in 2015.

Among the other functions occupied during his career, he has been appointed scientific deputy director general of the Institut Pasteur from 2006 to 2008, by the director general, Alice Dautry, and from 1997 to 2011 he was a senior member of the Institut Universitaire de France. He is Emeritus Professor at the Institut Pasteur.

Scientific achievements Bernard Dujon scientific work focuses on the genetic material of eukaryotic organisms, its organization, dynamics, functioning and evolution. Most of his work has used the yeast Saccharomyces cerevisiae, as experimental material, but he also got interested in studying other yeasts of biotechnological or medical interest, such as Kluyveromyces lactis and Candida glabrata.

The early years : discovery of the first homing endonuclease

In Gif-sur-Yvette, Bernard Dujon started to study a strange genetic phenomenon, linked to mitochondrial genetics, whose study was still in infancy.B. Dujon et al., « Mitochondrial Genetics. IX. A model for recombination and segregation of mitochondrial genomes in Saccharomyces cerevisiae », Genetics,‎ (1974) 78, p. 415-437 When crossing two haploid yeast species carrying different mitochondrial mutations, conferring the resistance to erythromycin or to chloramphenicol, allele segregation did not follow mendelian rules and recombinants appeared in mysterious proportions. At that time, no one had any idea of the genetic content of mitochondria, except that it contained DNA. Bernard Dujon was studying a particular mitochondrial locus, called omega, that could be present as two different alleles, omega+ or omega-. Genetic crosses between yeast cells carrying different alleles led to highly distorted inheritance in the progeny, since almost all cells ended up carrying the omega+ allele! In 1974, he proposed a model in which gene conversion of the omega- allele to omega+ was achieved by homologous recombination, replacing one allele by the other, copying in the process the flanking erythromycin and chloramphenicol mutations.

At about the same time, recombinant DNA technologies and restriction enzymes were discovered. In 1977, independent researches by Fred Sanger on one side and by Walter Gilbert and Allan Maxam on the other, led to the invention of two different methods to sequence DNA. Later the same year, introns were discovered. Thermal denaturation studies with François Michel, another student of Piotr Slonimski, suggested that omega could be an intron. Bernard Dujon contacted Walter Gilbert at Harvard University about the possibility to come to his lab for a short post-doctoral period, in order to sequence the omega locus. He moved to Harvard the following year and in 1979 achieved the sequence of what would become the first mobile intron to be described.B. Dujon, « Sequence of the intron and flanking exons of the mitochondrial 21S rRNA gene of yeast strains having different alleles at the omega and RIB 1 loci », Cell,‎ (1980) 20, p. 185-197 But the most surprising result was not that omega was indeed an intron, but that it contained an open reading frame, putatively encoding a 235 amino acid protein with no homology to any known protein. At that time, no intron was supposed to be coding. Could it be that the encoded protein played a role in the intron mobility between omega- and omega+ strains ?A. Jacquier and B. Dujon, « An intron encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene », Cell,‎ (1985) 41, p. 383-394

Back to Gif-sur-Yvette in 1981, Bernard Dujon set up a small team in an old lab space lent by Piotr Slonimski. François Michel rapidly joined him and later on Alain Jacquier, Hugues Blanc, Pierre Dehoux and Laurence Colleaux, as well as sabbatical visitors such as Walt Fangman from the University of Washington. They discovered that the omega intron was present in other yeast species collected in Harvard. Following the sequencing of several other introns, François Michel discovered that these introns could be folded into stem-loops whose structures (if not their sequences) were conserved. This suggested that they could be directly involved in the splicing mechanism by defining exon-intron junctions. In addition, they discovered that two different intronic structures existed, defining what they called group IB. Dujon, « Group I introns as mobile genetic elements: facts and mechanistic speculations – a review », Gene,‎ (1989) 82, p. 91-114 and group II introns, a nomenclature still in use today. They published their models of intron folding in Biochimie in 1982 and this article quickly became a reference for researchers in the field.

But the precise function of the omega-encoded protein was still unknown. Bernard Dujon decided to adapt the mitochondrial gene to the universal genetic code in order to be able to express it in a heterologous system. At that time, it was a real tour de force, since oligonucleotide synthesis and in vitro mutagenesis were uncommon and not available in Gif-sur-Yvette. Fortunately, Bernard Dujon met Francis Galibert, who was working at the Hôpital Saint Louis in Paris and who just came back from Fred Sanger laboratory to set up his own lab. At that time, he was the only one in France to be able to synthesize oligonucleotides. With the help of Francis Galibert's oligonucleotides, Bernard Dujon modified 26 of the 235 codons of the omega reading frame to adapt it to the universal genetic code. Synthesis of the resulting protein in Escherichia coli, in the presence of a plasmid carrying the omega-sequence showed without any ambiguity, in 1985, that the omega protein was a double-strand DNA endonuclease, as was predicted by the model 12 years ago.L. Colleaux et al., « Universal code equivalent of a yeast mitochondrial intron reading frame is expressed into E. coli as a specific double strand endonuclease », Cell,‎ (1986) 44, p. 521-533 This nuclease took afterwards the conventional name of I-SceI,L. Colleaux et al., « Recognition and cleavage site of the intron encoded omega transposase », Proc. Natl. Acad. Sc. USA,‎ (1988) 85, p. 6022-6026 the first intron homing endonuclease discovered, first of its kind but dozens of others would rapidly follow.

In 1987, a call for a yeast geneticist was published by the Institut Pasteur. Bernard Dujon applied and left Gif-sur-Yvette to move to Paris. In this new scientific environment, he used I-SceI to the purpose of making unique double-strand breaks in complex genomes, such as mouse, plants or the human genome, in collaboration with many scientists worldwide. In collaboration with the laboratory of Jean-François Nicolas at the Institut Pasteur, Arnaud Perrin and André Choulika (who would later become two founding members of the biotech company Cellectis) were able to do the first gene replacement in mouse cells using I-SceI,A. Choulika et al., « Induction of homologous recombination in mammalian chromosomes by using the I-Sce I system of Saccharomyces cerevisiae », Mol. Cell. Biol,‎ (1995) 15, p. 1968–1973 at the same time Maria Jasin in United States was doing similar experiments in human cells.

The yeast genome project

In 1988, André Goffeau, a Belgian yeast geneticist from the University of Louvain-la-Neuve convinced the European Commission to support the complete sequencing of the yeast genome. Under his management, 30 European laboratories collaborated to this endeavor. Their goal was to sequence 10 kb of DNA in two years of time, in order to complete chromosome III sequence, one of the smallest ones. Later on, they were joined by other labs worldwide to help sequencing the 15 other chromosomes. Bernard Dujon took an active part in this project and was one of the leading figures of the yeast program. He coordinated the sequencing of two chromosomes out of sixteen (XI and XV) and the map of a third chromosome (VII) was made by Hervé Tettelin, André Goffeau's student, using the I-SceI chromosome fragmentation technology developed in the meantime. The yeast genome sequence was completed in 1995 and published one year later. During the course of this project, it was discovered that one third of the sequenced genes had no homologue in any database (the so-called "orphans"). The extremely high level of gene redundancy, due -at least in part- to an ancient whole-genome duplication in the ancestor of Saccharomyces species, led to a new era in biology. Genomics, freshly born as a new science, will be studying entire genomes, instead of individual genes, and try to understand genome organization and evolution.

The Génolevures program

While Bernard Dujon was participating to the EUROFAN program, aiming at determining the function of all discovered genes, he started a completely different approach, based on yeast comparative genomics. Odile Ozier-Kalogeropoulos and her Master student, Alain Malpertuy, had produced 600 sequence reads of a yeast of biotechnological interest, Kluyveromyces lactis. This allowed them to identify hundreds of new genes by direct comparison with the S. cerevisiae genome. By analogy with Expressed Sequence Tags (EST) that were widely used at that time as a proxy to estimate the number of different human genes and their expression tissues, Alain Malpertuy coined these sequences Random Sequence Tags (RST) and the acronym was subsequently kept for further similar studies.