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The mutational profile of the yeast genome is shaped by replication.

TitleThe mutational profile of the yeast genome is shaped by replication.
Publication TypeJournal Article
Year of Publication2012
AuthorsAgier, N, Fischer, G
JournalMol Biol Evol
Volume29
Issue3
Pagination905-13
Date Published2012 Mar
ISSN1537-1719
KeywordsBase Composition, Computational Biology, DNA Replication, Genome, Fungal, Mutation Rate, Polymorphism, Single Nucleotide, Saccharomyces cerevisiae
Abstract

Despite the scrutiny that has been directed for years at the yeast genome, relatively little is known about the impact of replication on the substitution dynamics in Saccharomyces cerevisiae. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. In addition, we found a mutational asymmetry associated with the polarity of replication resulting in higher rates of substitutions toward C and A than toward G and T in leading strands (reciprocally more substitutions toward G and T in lagging strands). Such mutational asymmetries applied over long evolutionary periods should generate compositional skews between the two DNA strands. Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands). We also show that the nucleotide frequencies at mutational equilibrium predict a compositional skew at equilibrium very close to the observed skew between leading and lagging strands, suggesting that compositional equilibrium has been nearly attained in the present day genome of S. cerevisiae. Surprisingly, the direction of this skew is inverted compared with the one in the human genome.

DOI10.1093/molbev/msr280
Alternate JournalMol. Biol. Evol.
PubMed ID22114361