Late-replicating domains have higher divergence and diversity in Drosophila melanogaster

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Abstract

Several reports from mammals indicate that an increase in the mutation rate in late-replicating regions may, in part, be responsible for the observed genomic heterogeneity in neutral substitution rates and levels of diversity, although the mechanisms for this remain poorly understood. Recent evidence also suggests that late replication is associated with high mutability in yeast. This then raises the question as to whether a similar effect is operating across all eukaryotes. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. Given the availability of genome-wide replication timing profiles for D. melanogaster, we now return to this issue. Consistent with what is seen in other taxa, we find that divergence at synonymous sites in exon cores, as well as divergence at putatively unconstrained intronic sites, is elevated in late-replicating regions. Analysis of genes with low codon usage bias suggests a similar to 30% difference in mutation rate between the earliest and the latest replicating sequence. Intronic sequence suggests a more modest difference. We additionally show that an increase in diversity in late-replicating sequences is not owing to replication timing covarying with the local recombination rate. If anything, the effects of recombination mask the impact of replication timing. We conclude that, contrary to prior reports and consistent with what is seen in mammals and yeast, there is indeed a relationship between rates of nucleotide divergence and diversity and replication timing that is consistent with an increase in the mutation rate during late S-phase in D. melanogaster. It is therefore plausible that such an effect might be common among eukaryotes. The result may have implications for the inference of positive selection.
Original languageEnglish
Pages (from-to)873-882
Number of pages10
JournalMolecular Biology and Evolution
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Mutation Rate
Drosophila melanogaster
divergence
Eukaryota
mutation
Genetic Recombination
eukaryotic cells
Mammals
Yeasts
mammals
yeasts
eukaryote
Masks
S Phase
codons
Codon
interphase
recombination
exons
yeast

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Late-replicating domains have higher divergence and diversity in Drosophila melanogaster. / Weber, Claudia C; Pink, Catherine J; Hurst, Laurence D.

In: Molecular Biology and Evolution, Vol. 29, No. 2, 02.2012, p. 873-882.

Research output: Contribution to journalArticle

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