Unraveling evolutionary causes and consequences of quantitative variation of meiotic recombination – EVOLREC

Meiotic recombination is a key process that has major implications in genome evolution, dynamics of trait adaptation, and organismal fitness. Recombination events are unevenly distributed along the genome and crossover number and positioning are strongly regulated, but most of the underlying genetic determinants are still unknown. The numbers of crossovers per chromosome are very similar across species, even though there are huge differences in chromosome physical sizes, but surprisingly, the selective pressures driving this last constraint remain unclear. The interplay between recombination and adaptation is complex because recombination can modulate the speed of adaptation via exploiting standing genetic variation, and inversely, evolutionary processes leading to adaptation can indirectly drive changes in crossover rates. Specifically, high recombination may speed up adaptation by creating new favorable allelic combinations, but may also cause ‘recombination load’ by breaking such favorable haplotypes, for instance in clusters of co-evolved genes. There is some intra-specific quantitative variability of crossover number and positioning, due to polymorphism of TRANS acting genes and CIS sequence features, which suggests that recombination can evolve under selection. The main themes addressed in this project are (1) the capacity of recombination rate to evolve, (2) the CIS and TRANS genetic determinants driving quantitative changes in crossover number and positioning, and (3) the interplay between recombination and adaptation to stress. Using the model species S. cerevisiae, which has been instrumental in understanding many mechanisms of how meiotic recombination is regulated, we propose to map genomic loci that regulate recombination rate and crossover distribution using state-of-the-art methods and resources (fluorescent strains and high-throughput Fluorescence-Activated Cell Sorting of recombinant cells, ‘Multiparent Advanced Generation InterCross’ population) that the partners have recently developed. This will enable us for the first time to evolve in the laboratory differences in recombination rates at large-scale, and to investigate their fitness consequences. We will thus be able to quantitatively measure the response to recurrent directional selection for recombination rate, and to use a ‘pool-seq’ approach to dissect the genetic determinants underlying that response: after bulk deep-sequencing of the evolved and control populations, analysis of allele frequency profiles along the genome will reveal signatures of selection pointing to the localization of QTLs affecting global recombination in TRANS. In addition, tetrad sequencing will be used to obtain high-resolution recombination profiles to analyze the relationship between local recombination and CIS acting genomic sequence features. The selection experiment will produce evolved populations with both a large genetic basis and either high or low mean recombination rates. We will use these populations to investigate the interplay between recombination and adaptation through experimental evolution under salt stress. To this end, we will combine sexual and mitotic generations to evolve these populations while applying salt stress during vegetative growth phases. Finally, based on the previous results, we will develop mathematical models to predict recombination landscapes from the sequence, and use them to extrapolate our observations on the recombination-adaptation interplay to a wider range of situations. The great complementarity between the methods, biological resources, and skills of the partners, make this project an unprecedented opportunity to bring novel insights to the evolutionary causes and consequences of the quantitative variation of recombination, and to unravel the role recombination plays in stress adaptation.