Genomic and Epigenetic Interplay Drives Adaptive Fusion via Reproduction Trade-Off

Investment in sexual reproduction has long been seen as a fitness cost for asexual proliferation, raising the question of how cells evolve to accommodate cyclical demands of sexual and asexual cycles. We addressed this question by evolving Schizosaccharomyces pombe lacking the critical fusion gene Prm1 through 18 cycles of alternating meiosis and mitosis. Initially, transcriptional tweaks offered a fragile means to fuse despite Prm1's absence. However, a telomeric 1% genome deletion that epigenetically silenced Clr5 ultimately locked in a latent, Prm1 independent fusion pathway involving the mating regulator Ste11 and the pheromone MAPK scaffold Sms1. This adaptation, though efficient at restoring sexual reproduction, came at the cost of mitotic growth. By contrast, rationally constructing mutations in a synthetic evolution approach bypassed the trade off, enabling simultaneous high fusion efficiency and near wild type proliferation. Our findings illustrate how epigenetic derepression and genetic assimilation converge to create innovative solutions under cyclical selection pressures with trade offs.