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Mutation Hot Spots in Yeast Caused by Long-Range Clustering of Homopolymeric Sequences

Abstract

Evolutionary theory assumesthat mutations occur randomly in thegenome;however, studies performed in a variety of organismsindicate the existence of context-dependentmutation biases. Sources of mutagenesis variationacross large genomic contexts (e.g., hundreds ofbases) have not been identified. Here, we usehigh-coverage wholegenome sequencing of a conditionalmismatch repair mutant line of diploidyeast to identify mutations that accumulated after 160generations of growth.The vast majority of themutations accumulated as insertion/deletions(in/dels) in homopolymeric [poly(dA:dT)] andrepetitive DNA tracts. Surprisingly, the likelihood of an in/delmutation in a given poly(dA:dT) tract is increasedby the presence of nearby poly(dA:dT) tractsin up to a 1,000 bp region centered on the giventract. Our work suggests that specific mutation hot spotscan contribute disproportionately to the genetic variationthat is introduced into populations andprovides long-range genomic sequence context that contributes to mutagenesis.

Content

Authors :Xin Ma, MariaV. Rogacheva, Nishant K.T., Sarah Zanders, CarlosD. Bustamante, and Eric Alani
Year :2012
School :Biology
Genre :Jurnal Article
Journal :Cell Reports
Volume :1
Pages :36-42
DOI :http://dx.doi.org/10.1016/j.celrep.2011.10.003
ARXIV :http://arxiv.org/abs/