Abstract
Using competition experiments in continuous cultures grown in different nutrient environments (glucose limited, ammonium limited, phosphate limited and white grape juice), we identified genes that show haploinsufficiency phenotypes (reduced growth rate when hemizygous) or haploproficiency phenotypes (increased growth rate when hemizygous). Haploproficient genes (815, 1,194, 733 and 654 in glucose-limited, ammonium-limited, phosphate-limited and white grape juice environments, respectively) frequently show that phenotype in a specific environmental context. For instance, genes encoding components of the ubiquitination pathway or the proteasome show haploproficiency in nitrogen-limited conditions where protein conservation may be beneficial. Haploinsufficiency is more likely to be observed in all environments, as is the case with genes determining polar growth of the cell. Haploproficient genes seem randomly distributed in the genome, whereas haploinsufficient genes (685, 765, 1,277 and 217 in glucose-limited, ammonium-limited, phosphate-limited and white grape juice environments, respectively) are over-represented on chromosome III. This chromosome determines a yeast's mating type, and the concentration of haploinsufficient genes there may be a mechanism to prevent its loss.
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Acknowledgements
This work was supported by grants from the Natural Environment Research Council (NERC) to S.G.O., G.G. and D.B.K., and by the Consortion for the Functional Genomics of Microbial Eukaryotes (COGEME; Coordinator, S.G.O.), funded by the Investigating Gene Function Initiative of the Biotechnology and Biological Sciences Research Council (BBSRC), and a BBSRC project grant to S.G.O. and D.B.K. D.D. is a NERC Advanced Fellow. K.G. holds a Wellcome Trust PhD studentship. We thank C. Reeves, P. Pir, J. Wu and M. Barton for communicating their unpublished data. We thank T. Carr (Sussex), D. Charlesworth (Edinburgh), L. Hurst (Bath) and B. Papp (Szeged) for stimulating discussions.
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Supplementary Text and Figures
Supplementary Methods, Supplementary Note, Supplementary Figure 1 (PDF 559 kb)
Supplementary Table 1
List of strains whose TAGs give weak signal (XLS 18 kb)
Supplementary Table 2
List of strains lost in batch culture (XLS 12 kb)
Supplementary Table 3
Strains showing severe haploinsufficiency (XLS 25 kb)
Supplementary Table 4
Strains showing haploinsufficiency or haploproficiency in all conditions (XLS 545 kb)
Supplementary Table 5
Nitrogen content of grape juice and the chemically defined media (XLS 20 kb)
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Delneri, D., Hoyle, D., Gkargkas, K. et al. Identification and characterization of high-flux-control genes of yeast through competition analyses in continuous cultures. Nat Genet 40, 113–117 (2008). https://doi.org/10.1038/ng.2007.49
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DOI: https://doi.org/10.1038/ng.2007.49
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