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About: All organisms are subject to spontaneous mutation, but we are just beginning to explore how DNA replication and repair processes evolve to determine the mutation rate and spectrum. My lab uses multiple yeast species and cell types to understand how the mutation process is influenced by sequence contexts within genomes, such as repetitive DNA, and by population genetic forces like natural selection and genetic drift. We studied many experimental strains of the budding yeast Saccharomyces cerevisiae to examine how ribosomal DNA, which is highly repetitive but critical for cellular function, maintains its structure despite significant mutational pressures. Our data supports a model of rDNA maintenance where persistent copy loss is counteracted by directed-mutation mechanisms, which themselves represent a large mutational target. We find that a model of mutation-selection balance is adequate to explain levels of standing variation in rDNA copy number in the wild. We have also been comparing species and cell types to test hypotheses for the evolution of genome-wide mutation rates. In S. cerevisiae, which generally lives as a diploid, we previously found that haploid cells exhibited an elevated mutation rate and altered mutational spectrum. We now have complementary evidence from the fission yeast Schizosaccharomyces pombe, which generally lives as a haploid. For this species, we find that the mutation rate is elevated in diploid cells. This indicates that natural selection usually pushes mutation rates to be lower but has a limited opportunity to do so in rare cell types, supporting a key hypothesis regarding the role of drift in mutation rate evolution.
WEBSITE: https://sharp.genetics.wisc.edu/

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