Mobile Gene Regulation in Natural Populations – GENEMOBILE

The number of sequenced genomes has greatly increased in the last years, with each additional genome sequenced clearly establishing the importance of transposable elements (TEs) in most genomes. These middle repeated DNA sequences are able to move around genomes, i.e. to transpose, and are thus important partners in genome evolution. They significantly contribute to the modern vision of the genome as a dynamic system. In drosophila, TEs constitute about 15% of the genome, and are responsible for around 50 to 80% of the observed spontaneous mutations. The human genome is composed of at least 50% of TEs (those that are still detectable) but the rate of induced mutations drops to 1 to 2%. We now know that these elements are extremely important in reshaping the genomes, creating the variability necessary for population adaptation and species evolution. The difference in the mutation rates between flies and humans shows the genomic adaptation of the host organism to regulate the invasive capacity of these elements and their mutational capability. One of the most important and fundamental questions in population genetics and functional genetics is thus to understand how genomes and populations control the TE activity. The aim of this grant proposal is to understand the impact of TEs on genome evolution, both at the population and species levels. The interactions between TEs and host genomes are still far from being understood, but this may eventually be the key to understand genotype-by-environment interactions (Biémont and Vieira 2006). We thus propose two approaches to get a deeper knowledge on the dialogue between TEs and hosts, using our model system in D. melanogaster and D. simulans natural populations. The first approach is to deeply analyze at the molecular and functional levels the copies of the set of TEs mentioned above. We need to characterize the status of each element in different populations regarding copies location (euchromatin vs heterochromatin), to determine the expression of the elements in different tissues and developmental stages at the RNA and protein levels, and to make transposition assays. The second approach concerns the host regulation mechanisms of TEs. We will look at the epigenetic factors that may be responsible for an increase of TE activity and genome invasions. We could thus associate a structure (physical feature) of the TEs with an epigenetic control (chemical modification). This population-molecular genetics analysis will be supported by a bioinformatics approach that will characterize TE sequences in the sequenced genomes of 1) Drosophila melanogaster and D. simulans, 2) the 10 other Drosophila genomes so far sequenced (or underway), and in genomes of other insects (Anopheles, honeybee, silkworm), 3) in the genomes of different individuals of D. simulans that will soon be publicly available. We will thus get a complete picture of the evolutionary history of these TEs and the pattern of deletion/substitution acting on the copies. Bioinformatics tools will also be used in order to support molecular analyses. Since the 80', when TEs were mostly considered as junk DNA, a huge transition has been operating about the way we see the genomic impacts of these elements. It is now clear that even if TEs are most often deleterious to the host, the genetic variability induced by their presence and their transposition is a very strong force for genome evolution. We are, however, still unable to deeply understand how TEs are activated and what promote the waves of TE transposition/inactivation in the host genome.The present program is aimed to get some clues on how specific elements are regulated in species and populations. The selected TEs belong to different families that are good representatives of endogenous retoviruses and LINE-like elements. By comparing the dynamics of these TEs, we will better understand how genomes evolve and at what speed this evolution occurs.