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Slow growth and increased spontaneous mutation frequency in respiratory deficient afo1- yeast suppressed by a dominant mutation in ATP3.

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journal contribution
posted on 2020-12-04, 12:53 authored by Jing Li, Mark Rinnerthaler, Johannes Hartl, Manuela Weber, Thomas Karl, Hannelore Breitenbach-Koller, Michael Mülleder, Jakob Vowinckel, Hans Marx, Michael Sauer, Diethard Mattanovich, Özge Ata, Sonakshi De, Gregor P Greslehner, Florian Geltinger, Bill Burhans, Chris Grant, Victoria Doronina, Meryem Ralser, Maria Karolin Streubel, Christian Grabner, Stefanie Jarolim, Claudia Moßhammer, Campbell W Gourlay, Jiri Hasek, Paul J Cullen, Gianni Liti, Markus Ralser, Michael Breitenbach
A yeast deletion mutation in the nuclear-encoded gene, AFO1, which codes for a mitochondrial ribosomal protein, led to slow growth on glucose, the inability to grow on glycerol or ethanol, and loss of mitochondrial DNA and respiration. We noticed that afo1- yeast readily obtains secondary mutations that suppress aspects of this phenotype, including its growth defect. We characterized and identified a dominant missense suppressor mutation in the ATP3 gene. Comparing isogenic slowly growing rho-zero and rapidly growing suppressed afo1- strains under carefully controlled fermentation conditions showed that energy charge was not significantly different between strains and was not causal for the observed growth properties. Surprisingly, in a wild-type background, the dominant suppressor allele of ATP3 still allowed respiratory growth but increased the petite frequency. Similarly, a slow-growing respiratory deficient afo1- strain displayed an about twofold increase in spontaneous frequency of point mutations (comparable to the rho-zero strain) while the suppressed strain showed mutation frequency comparable to the repiratory-competent WT strain. We conclude, that phenotypes that result from afo1- are mostly explained by rapidly emerging mutations that compensate for the slow growth that typically follows respiratory deficiency.


Crick (Grant ID: 10134, Grant title: Ralser FC001134) Wellcome Trust (Grant ID: 200829/Z/16/Z, Grant title: WT 200829/Z/16/Z)