Heterosis as a consequence of regulatory incompatibility

Rebecca H. Herbst, Dana Bar-Zvi, Sharon Reikhav, Ilya Soifer, Michal Breker, Ghil Jona, Eyal Shimoni, Maya Schuldiner, Avraham A. Levy*, Naama Barkai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Heterosis is typically viewed as the opposite of hybrid incompatibility. In this view, the superior performance of the hybrid is attributed to heterozygote combinations that compensate for deleterious mutations accumulating in each individual genome, or lead to new, over-dominating interactions with improved performance. Still, only fragmented knowledge is available on genes and processes contributing to heterosis.

Results: We describe a budding yeast hybrid that grows faster than both 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 increased signs of DNA damage. A systematic genetic screen identified hundreds of S. cerevisiae alleles whose deletion reduced growth of the hybrid. These growth-affecting alleles were condition-dependent, and differed greatly from alleles that reduced the growth of the S. cerevisiae parent.

Conclusions: Our results define a budding yeast hybrid that is perturbed in multiple regulatory processes but still shows a clear growth heterosis. We propose that heterosis results from incompatibilities that perturb regulatory mechanisms, which evolved to protect cells against damage or prepare them for future challenges by limiting cell growth.

Original languageEnglish
Article number38
Number of pages15
JournalBMC Biology
Volume15
DOIs
Publication statusPublished - 11 May 2017

Funding

The electron microscopy studies were conducted at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging (Weizmann Institute of Science). We thank members of our groups for discussions and Gilgi Friedlander for help with bioinformatics data processing. This work was supported by grants from the ERC, ISF, Minerva Center, ICORE, and the Helmsley charitable trust. This work was supported by grants from the ERC, ISF, Minerva Center, ICORE, and the Helmsley charitable trust. RHH, DB, NB, and AL designed the experiments and drafted the manuscript. RHH performed and analyzed the pooled library screen experiments. DB and ES performed and analyzed the electron microscopy experiments. DB and GJ performed and analyzed the fermenter experiments. DB, SR, and IS performed and analyzed the cell cycle experiments. MB performed and analyzed the protein localization screen. MS discussed data interpretation; NB and AL supervised the study. All authors read and approved the final manuscript.

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