Blanc SVSE 6 - Blanc - SVSE 6 - Génomique, génétique, bioinformatique et biologie systémique

Dynamics and evolution of yeast genomes, unicellular eukaryotic models. – DYGEVO

Genome instabilities, genetic diseases and fungal infections

Copy number variations play an important role in genome evolution and genetic diseases such as cancer. Using yeast as exprmental model, we study the mechanisms involved. Furthermore, we analyze the role of repetitive elements in the pathogenicity of some yeasts.

Basic research on genomes based on model organisms

In an international context of rapid progress on genomes, particularly the human one and its genetic alterations in cancers, we study the mechanisms involved using the yeast Saccharomyces cerevisae, presently the best known eukaryotic organism for genomics and allowing the study of rare phenomena over long periods.

Yeast genomes are easily characterized comprehensively by novel deep sequencing methods. All types of alterations can be identified in genomes of mutants isolated from different experiments. Furthermore, yeast genome scan be manipulated indefinitely, offering us tools for functional analysis.

About the genome stability issue, we have discovered a new phenomenon of massive amplification allowing very unfit cells to recover nearly normal growth rates. This phenomenon is being studied.
About the functional issue, we have shown the role of repetitive sequences in cell adhesion, a critial aspect for fungal infections. We are presently studying the origin of these repetitive sequences.

This is a basic research program far upstream of immediate applications. Its impact is to be found on the long term by important progress of our understanding based on our results and by their stimulating effects for further investigations. Beyond basic aspects, one can imagine a significant impact of our reslts on cancers and fungal infections.

Our scientific production is made of publications in international journals (presently one published, on in press and two others in preparation), teaching young scientists (one PhD theiss and several Masters), scientific exchanges with french and foreign colleagues (presentations at international meetings and scientific collaborations).

Genomes can now be studied with a precision, comprehensiveness and scale unknown before. If the general functional organization of eukaryotic genomes suggest that they all share common mechanistic and evolutionary principles, genomes of unicellular eukaryotes reveal a large diversity whose origin may be related to their population size and mode of reproduction, often favoring clonal expansions over regular sexual cycles. Among those, yeasts offer an interesting group to study this problem. These unicellular fungi are often amenable to precise laboratory experiments whose results can be interpreted against the numerous genomic data now available among a phylum covering a very large evolutionary range. This project takes advantage of this situation to examine basic mechanisms of eukaryotic genome dynamics and their role in the evolution of these unicellular organisms. The project is primarily based on the construction of novel genotypes by interspecific replacement of essential orthologous genes, whole-genome fusions or insertion of specific heterologous sequences, followed by laboratory evolution experiments to monitor the spontaneous genomic changes occurring from these constructs. The panoply of yeast genome sequences available offers us an important choice for such experiments addressing yet poorly examined questions of yeast evolutionary genomics: -i- how the flexibility of yeast genomes is used to increase cell fitness when simple nucleotide changes have a low probability to do so; -ii- what can be the role of interspecific genetic exchanges in the evolution of eukaryotic microorganisms and –iii- what is the origin and possible adaptive function of long tandem repeats observed in protein-coding sequences of some yeast species, often pathogenic ones. Three series of experiments are planned and constitute three independent tasks of this proposal with possible interconnected results.



Project coordination

Bernard DUJON (INSTITUT PASTEUR) – bdujon@pasteur.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

IP INSTITUT PASTEUR

Help of the ANR 355,000 euros
Beginning and duration of the scientific project: September 2011 - 36 Months

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