The mutation spectrum in genomic late replication domains shapes mammalian GC content.

ABSTRACT: Genome sequence compositions and epigenetic organizations are correlated extensively across multiple length scales. Replication dynamics, in particular, is highly correlated with GC content. We combine genome-wide time of replication (ToR) data, topological domains maps and detailed functional epigenetic annotations to study the correlations between replication timing and GC content at multiple scales. We find that the decrease in genomic GC content at large scale late replicating regions can be explained by mutation bias favoring A/T nucleotide, without selection or biased gene conversion. Quantification of the free dNTP pool during the cell cycle is consistent with a mechanism involving replication-coupled mutation spectrum that favors AT nucleotides at late S-phase. We suggest that mamm

SUBMITTER: Kenigsberg E 

PROVIDER: S-EPMC4872117 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature