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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 mammalian GC content composition is shaped by independent forces, globally modulating mutation bias and locally selecting on functional element. Deconvoluting these forces and analyzing them on their native scales is important for proper characterization of complex genomic correlations.

SUBMITTER: Kenigsberg E

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

REPOSITORIES: biostudies-literature

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

Kenigsberg Ephraim E Yehuda Yishai Y Marjavaara Lisette L Keszthelyi Andrea A Chabes Andrei A Tanay Amos A Simon Itamar I

Nucleic acids research 20160416 9

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 ...[more]

PMID: 27085808

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Project description:Bacterial evolution is characterized by strong purifying selection as well as rapid adaptive evolution in changing environments. In this context, the genomic GC content (genomic GC) varies greatly but presents some level of phylogenetic stability, making it challenging to explain based on current hypotheses. To illuminate the evolutionary mechanisms of the genomic GC, we analyzed the base composition and functional inventory of 11,083 representative genomes. A phylogenetically constrained bimodal distribution of the genomic GC, which mainly originated from parallel divergences in the early evolution, was demonstrated. Such variation of the genomic GC can be well explained by DNA replication and repair (DRR), in which multiple pathways correlate with the genomic GC. Furthermore, the biased conservation of various stress-related genes, especially the DRR-related ones, implies distinct adaptive processes in the ancestral lineages of high- or low-GC clades which are likely induced by major environmental changes. Our findings support that the mutational biases resulting from these legacies of ancient adaptation have changed the course of adaptive evolution and generated great variation in the genomic GC. This highlights the importance of indirect effects of natural selection, which indicates a new model for bacterial evolution. IMPORTANCE GC content has been shown to be an important factor in microbial ecology and evolution, and the genomic GC of bacteria can be characterized by great intergenomic heterogeneity, high intragenomic homogeneity, and strong phylogenetic inertia, as well as being associated with the environment. Current hypotheses concerning direct selection or mutational biases cannot well explain these features simultaneously. Our findings of the genomic GC showing that ancient adaptations have transformed the DRR system and that the resulting mutational biases further contributed to a bimodal distribution of it offer a more reasonable scenario for the mechanism. This would imply that, when thinking about the evolution of life, diverse processes of adaptation exist, and combined effects of natural selection should be considered.

Dataset Information

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

Publications

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

Similar Datasets

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