Inheriting an extra chromosome can sometimes be disastrous, but in the September issue of G3, Linder et al. investigate a chromosome duplication that helps yeast survive harsh conditions. Yeast with an extra copy of chromosome IV better tolerate hydrogen peroxide exposure, largely thanks to an extra copy of a gene that detoxifies the chemical. This work shows how large spontaneous mutations can help organisms thrive in the absence of natural genetic variation.
To generate mutants tolerant of hydrogen peroxide, the researchers plated haploid yeast (which have one copy of each chromosome) from three different strains on agar dosed with hydrogen peroxide. They chose thirty-seven colonies that tolerated higher concentrations of peroxide than their parent strains. Whole genome sequencing of those tolerant colonies revealed nearly half of them carried a duplication of chromosome IV, making it the most common mutation overall.
One colony had a duplication of the right arm of chromosome IV, allowing researchers to limit their search for the beneficial genes to just this area. They further narrowed down the search by systematically deleting portions of the right arm of the chromosome. Eventually, they targeted a region containing only five genes. Knocking them out one by one revealed most of these colonies’ resistance to hydrogen peroxide was due to an extra copy of the peroxidase gene TSA2, which is an enzyme that detoxifies peroxide. Boosting levels of TSA2 in parental cells increased their hydrogen peroxide tolerance, though not as much as the mutants carrying the whole duplicate chromosome. This means other unidentified factors on chromosome IV must also contribute to the phenotype.
This research shows chromosome duplication can be beneficial rather than harmful when the dosage of critical genes is increased. It all depends on the environment; in normal conditions, the hydrogen peroxide resistant mutants grew more slowly than their progenitors. Other studies in yeast have shown similar results for different stressors, suggesting spontaneous chromosome duplication may be commonly used by these microbes to quickly bridge the survival gap in tough environments.
The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial Chromosomal Duplication in Saccharomyces cerevisiae
Robert A. Linder, John P. Greco, Fabian Seidl, Takeshi Matsui and Ian M. Ehrenreich