PT - JOURNAL ARTICLE AU - Rebecca H. Herbst AU - Dana Bar-Zvi AU - Sharon Reikhav AU - Ilya Soifer AU - Michal Breker AU - Ghil Jona AU - Eyal Shimoni AU - Maya Schuldiner AU - Avraham Levy AU - Naama Barkai TI - Large-scale rewiring in a yeast hybrid AID - 10.1101/100263 DP - 2017 Jan 01 TA - bioRxiv PG - 100263 4099 - http://biorxiv.org/content/early/2017/01/13/100263.short 4100 - http://biorxiv.org/content/early/2017/01/13/100263.full AB - The merging of genomes in inter-specific hybrids can result in novel phenotypes, including increased growth rate and biomass yield, a phenomenon known as heterosis. We describe a budding yeast hybrid that grows faster than its parents under different environments. Phenotypically, the hybrid progresses more rapidly through cell cycle checkpoints, relieves the repression of respiration in fast growing conditions, does not slow down its growth when presented with ethanol stress, and shows increasing signs of DNA damage. A systematic genetic screen identified hundreds of alleles affecting hybrid growth whose identity vastly differed between the hybrid and its parent and between growth conditions. This large-scale rewiring of allele effects suggests that despite showing clear heterosis, the hybrid is perturbed in multiple regulatory processes. We discuss the possibility that incompatibilities contribute to hybrid vigor by perturbing safeguard mechanisms that limit growth in the parental background.