title: Mutation hot spots in yeast caused by long-range clustering of homopolymeric sequences.
abstract: Evolutionary theory assumes that mutations occur randomly in the genome; however, studies performed in a variety of organisms indicate the existence of context-dependent mutation biases. Sources of mutagenesis variation across large genomic contexts (e.g., hundreds of bases) have not been identified. Here, we use high-coverage whole-genome sequencing of a conditional mismatch repair mutant line of diploid yeast to identify mutations that accumulated after 160 generations of growth. The vast majority of the mutations accumulated as insertion/deletions (in/dels) in homopolymeric [poly(dA:dT)] and repetitive DNA tracts. Surprisingly, the likelihood of an in/del mutation in a given poly(dA:dT) tract is increased by the presence of nearby poly(dA:dT) tracts in up to a 1,000 bp region centered on the given tract. Our work suggests that specific mutation hot spots can contribute disproportionately to the genetic variation that is introduced into populations and provides long-range genomic sequence context that contributes to mutagenesis.
authors: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
authors: Xin
authors: X
authors: Ma
authors: Maria V
authors: MV
authors: Rogacheva
authors: K T
authors: KT
authors: Nishant
authors: Sarah
authors: S
authors: Zanders
authors: Carlos D
authors: CD
authors: Bustamante
authors: Eric
authors: E
authors: Alani
mesh_terms: D001483:Base Sequence; D020090:Chromosome Segregation / Q000235:genetics; D016000:Cluster Analysis; D010450:Endopeptidases / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D016681:Genome, Fungal / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D054643:INDEL Mutation / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011067:Poly dA-dT / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013172:Spores, Fungal / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: C084434:DOA4 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; D011067:Poly dA-dT; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase