Domestication drives repeated evolution of sexual–asexual life cycle trade-offs in yeast

For thousands of years, humans have domesticated animals and cultivated crops by managing reproduction and selecting for desirable traits. In contrast, microbial domestication has often occurred unintentionally, and the variation of life cycle as well as its impact on genome evolution remain poorly understood. Here, we systematically examined life cycle variation across a diverse panel of 771 diploid <i><i>Saccharomyces cerevisiae</i></i> isolates from both wild and domesticated lineages. We identified widespread alterations in sexual reproduction, including impairments of sporulation, spore viability, and mating-type switching. These changes led to the emergence of two distinct life cycle strategies, favoring either asexual or sexual reproduction, which were notably enriched in domesticated clades. Haplotype analyses of the <i>HO</i> mating-type switching gene revealed multiple, independent loss-of-function mutations, indicating convergent evolution of heterothallism. While a preference for sexual life cycle often correlated with increased genomic heterozygosity in domesticated and human-associated clades, this relationship was not uniform across all lineages. We propose that the co-occurrence of altered sexual and asexual cycle preferences results in a trade-off that balances outcrossing and the subsequent maintenance of heterozygosity in domesticated populations. Finally, we provide a CRISPR-based molecular toolbox and a stable haploid strain collection spanning global genetic diversity, enabling further genetic research and industrial applications.