Hybrid adaptation is hampered by Haldane's sieve.

Hybrids between species exhibit plastic genomic architectures that could foster or slow down their adaptation. When challenged to evolve in an environment containing a UV mimetic drug, yeast hybrids have reduced adaptation rates compared to parents. We find that hybrids and their parents converge onto similar molecular mechanisms of adaptation by mutations in pleiotropic transcription factors, but at a different pace. After 100 generations, mutations in these genes tend to be homozygous in the parents but heterozygous in the hybrids. We hypothesize that a lower rate of loss of heterozygosity (LOH) in hybrids could limit fitness gain. Using genome editing, we first demonstrate that mutations display incomplete dominance, requiring homozygosity to show full impact and to entirely circumvent Haldane's sieve, which favors the fixation of dominant mutations. Second, tracking mutations in earlier generations confirmed a different rate of LOH in hybrids. Together, these findings show that Haldane's sieve slows down adaptation in hybrids, revealing an intrinsic constraint of hybrid genomic architecture that can limit the role of hybridization in adaptive evolution.