Meiotic recombination is a key aspect of our biology. By ensuring proper chromosome segregation during meiosis and maintaining genome integrity, it plays a crucial role in our fecundity. Recombination also has an essential long-term evolutionary function, facilitating adaptation through linkage dissipation. However, recent progress in our understanding of the underlying molecular mechanisms suggests that recombination also has a dark side. Intra-genomic conflicts, mediated by two particular forms of meiotic drive called biased gene conversion, causing transmission biases at the level of the population, are now suspected to stand at the core of the dynamics of recombination. Such intra-genomic conflicts have a strong impact on the proper functioning of recombination and meiosis, as well as on genome-wide fitness landscapes, potentially contributing a substantial genetic load. More fundamentally, these conflicts are intrinsically the result of an interplay between the molecular mechanisms involved in the regulation of recombination and the long-term effects of biased gene conversion at the level of the population. As a consequence, recombination stands at the crossroad between molecular, cellular and evolutionary biology, and a full understanding of its regulation requires an integrated perspective, articulating together multiple domains of modern biology. This multi-disciplinary collaborative research project aims to arrive at an integrated understanding of recombination and biased-gene conversion, including their regulation, their impact on genome structure and their consequences on fitness, health and fecundity. The project will combine experimental, population genetic and comparative genomic approaches. It will be focused primarily on mammals and humans, while benefiting from a macro-evolutionary perspective. Its main contributions will be as follows. First, the current working model of the dynamics of recombination in mammals (the Red Queen model), which fully accounts for intra-genomic conflicts and biased gene conversion, will be extensively tested using a combination of experimental approaches (ChipSeq, sperm typing and high throughput sequencing) and comparative analyses. In parallel, statistical population genetic and phylogenetic approaches will be developed, leading to new bioinformatic tools allowing unbiased characterization of genomic fitness landscapes and selective regimes acting on protein-coding genes, correcting for the confounding effects of biased gene conversion. Finally, the taxonomic distribution and the ultimate causes of biased gene conversion will be investigated, using a combination of experimental, comparative and theoretical approaches. Altogether, this project will therefore arrive at an integrated understanding of recombination and gene conversion, organizing the proximal causes and the ultimate drivers into a coherent global view. Relying on ambitious sequencing projects, it will produce important new data pertaining to key aspects of these biological questions. It will also lead to the development of improved statistical and bioinformatic tools for decoding functional and selective features of genomes, and will therefore have a substantial impact on current bioinformatics and applied genomics. The project will be conducted by a multi-disciplinary consortium gathering four French research teams, based in Lyon (LBBE, Lartillot and Duret; LEM, Nesme) and Montpellier (IGH, de Massy; ISEM, Galtier), with complementary expertise in molecular, cellular, computational and evolutionary biology. A total budget of ~ 580 000 euros is requested.