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The CNRGH is the French national research center which enables a response to scientific questions necessitating high throughput sequencing and genotyping thanks to the development and deployment of innovative integrated technologies. The organization of the CNRGH enables optimization of genetic and genomic research on human diseases by creating indispensable links between cohort constitution (DNA samples), identification of the responsible genes, and study of the transcriptome and epigenome.
List of the main projects of the Institut de Génomique
From an evolutionary point of view, the algae are a heterogeneous group and include organisms from several distinct lineages. The brown algae, or class Phaeophyceae, are part of a group of organisms called the heterokonts (which also includes diatoms and oomycetes) and are only very distantly related to green and red algae (Baldauf, 2003). The vast majority of brown algae occur in marine environments. All members of the group are multicellular, with morphologies ranging from uniseriate branched filaments to complex parenchymatous thalli with multiple cell types, including conducting tissue. The thallus of the kelp Macrocystis pyrifera, for example, can reach up to 70 metres in length. The colour of brown algae is due to the presence of fucoxanthin, a xanthophyll pigment and the principal carbohydrate reserve is laminaran (rather than starch). In addition to cellulose, the cell walls of brown algae contain a variety of other polysaccharides including alginates and fucans.
Life cycles and mating types - In addition to being of general interest as complex multicellular organisms, brown algae exhibit several novel features particularly in relation to their life cycles and mating behaviour. Life cycles range from diplontic in Fucus to the nearly isomorphic, haploid-diploid life cycle of Ectocarpus whereas their sexual systems include both dioecious and hermaphrodite states and isogamy, anisogamy or oogamy. Haploid-diploid life cycles like that of Ectocarpus are of particular interest because they imply the existence of genetic control mechanisms that regulate the deployment of the two alternative, independent developmental programmes, influencing development at the level of the whole organism.
Early embryogenesis - Fertilisation is external in brown algae, involving fusion of naked gametes that have been released into the surrounding seawater. This feature has been exploited widely to study many aspects of early development including gamete fusion at fertilisation, establishment of polarity, the involvement of cell walls in early developmental signalling, initiation of the first cell cycle, coupling between the cell cycle and developmental processes and other aspects of development during early embryogenesis (Berger et al., 1994; Bouget et al., 1998; Corellou et al., 2000, 2001; Brownlee et al., 2001). Several cellular phenomena are highly novel in this group; cytokinesis, for example, has been shown to exhibit features typical of both animals and terrestrial plants (Nagasato and Motomura, 2002).
Endosymbiosis and the origin of chloroplasts - The chloroplasts of green plants and red algae are thought to be derived from an ancient cyanobacterium that was engulfed by a eukaryotic host cell. The chloroplasts of heterokonts, such as the brown algae, have a more complicated origin. They have been acquired via a secondary endosymbiotic event in which a chloroplast-containing organism similar to a red alga was itself engulfed by another eukaryote (Yoon et al., 2002). This convoluted history, which has left brown algal chloroplasts with several unusual features such as the four concentric membranes that surround the organelle, involved several phases of transfer of genes to the nucleus. The Ectocarpus genome sequence will allow these events to be traced at the gene level.
Responses to biotic and abiotic stress - The rocky shore habitats of most brown algae are stressful environments in which these organisms are subjected to both biotic aggression from grazers and pathogens and various abiotic stresses including large variations in temperature, immersion, light irradiation and mechanical forces. In consequence, the brown algae represent novel model systems for several aspects of responses to biotic and abiotic stresses including innate immunity (Potin et al., 2002), viral infection (Müller et al., 1998; Delaroque et al., 2001), novel pathosystems (Küpper et al., 2001, 2002; Maier et al., 2000) and osmotic stress (Coelho et al., 2002).
Industrial uses and production of bioactive molecules - In addition to the above fundamental points of interest, it is important to note that seaweeds also represent a marine resource with a wide range of uses in the food, cosmetic, and fertiliser industries and an estimated annual global value of about 4.5x109 euros (McHugh, 2003). They are also attracting increasing attention as a novel source of bioactive molecules, one example being IODUS 40, a formulation that is derived from a storage glucan of Laminaria digitata and which stimulates the natural defence responses of crop plants.
algae from the orders Laminariales and Fucales have been studied extensively in
the past but such models are poorly adapted for genomic and genetic approaches
because of their large genomes (ca. 700 and 1100 Mbp, respectively) and because
it is very difficult to complete their life cycles in the laboratory. To
address this problem, a survey of brown algal species was carried out in
Roscoff (Peters et al., 2004a) and this led to the choice of the
filamentous alga, Ectocarpus siliculosus, previously studied over
many years by Dieter Müller at the University of Konstanz, as a model species
for this group. The
choice of Ectocarpus was based on several characteristics including its small size, the fact that the entire life cycle can be completed in Petri dishes in the laboratory (Müller et a.l, 1998), its high fertility and rapid growth (the life cycle can be completed in 2-3 months), the ease with which genetic crosses can be carried out (Peters et al., 2004b) and the relatively small size of the genome. Moreover, the Ectocarpales are closely related to the most economically important brown algal group, the Laminariales (Draisma et al., 2003). Several classical and molecular genetic tools are being developed for Ectocarpusincluding transformation and RNA interference protocols. Mutant lines can be created by UV irradiation and screens for mutants are greatly facilitated by existence of a haploid phase in the life cycle.
The size of the genome of Ectocarpus siliculosus has been estimated to be 214 Mb. Whole genome random shotgun sequencing will be carried out by Genoscope with a coverage of 10 genome equivalents, for a volume of 4 300 000 reads using several plasmid libraries constructed at Genoscope with 3 and 10 kb inserts.
In parallel, Genoscope will sequence 100 000 cDNAs from libraries constructed at different stages of the life cycle: young and mature sporophytes, young gametophytes and protoplasts.
Patrick Wincker : pwincker .. At .. genoscope.cns.fr (Genoscope) - Mark Cock : cock .. At .. sb-roscoff.fr (UMR 7139, Roscoff)
Laboratories involved: Laboratory for the Genomic Analysis of Eukaryotes , Sequencing Laboratory
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.