Genome Destabilizing Mutator Alleles Drive Specific Mutational Trajectories in Saccharomyces cerevisiae

摘要: In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How alleles influence nature position accumulated a genomic context is largely unknown. Understanding impact particularly relevant cancer genomes where biased signatures are identifiable. We first created more complete picture cellular pathways that mutation rate using primary screen identify essential Saccharomyces cerevisiae gene cause mutator phenotypes. Drawing primarily on new identified this resource, we measure diverse patterns directly by whole-genome sequencing 68 mutation-accumulation strains derived from wild-type 11 parental genotypes. The differ across strains, displaying base-substitution biases, allele-specific hotspots, break-associated clustering. For example, mutants POLα Cdc13–Stn1–Ten1 complex, find distinct subtelomeric bias for show independent target sequence. Together our data suggest genome-instability sufficient drive discrete signatures, some which share properties with seen tumors. Thus, population cells, could clonal evolution establishing trajectories