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Evolution of replication origins in vertebrate genomes: rapid turnover despite selective constraints

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Item Type:Article
Title:Evolution of replication origins in vertebrate genomes: rapid turnover despite selective constraints
Creators Name:Massip, F. and Laurent, M. and Brossas, C. and Fernández-Justel, J.M. and Gómez, M. and Prioleau, M.N. and Duret, L. and Picard, F.
Abstract:The replication program of vertebrate genomes is driven by the chromosomal distribution and timing of activation of tens of thousands of replication origins. Genome-wide studies have shown the association of origins with promoters and CpG islands, and their enrichment in G-quadruplex motifs (G4). However, the genetic determinants driving their activity remain poorly understood. To gain insight on the constraints operating on origins, we conducted the first evolutionary comparison of origins across vertebrates. We generated a genome-wide map of chicken origins (the first of a bird genome), and performed a comparison with human and mouse maps. The analysis of intra-species polymorphism revealed a strong depletion of genetic diversity at the core of replication initiation loci. This depletion is not linked to the presence of G4 motifs, promoters or CpG islands. In contrast, we show that origins experienced a rapid turnover during vertebrate evolution, since pairwise comparisons of origin maps revealed that <24% of them are conserved among vertebrates. This study unravels the existence of a novel determinant of origins, the precise functional role of which remains to be determined. Despite the importance of replication initiation for the fitness of organisms, the distribution of origins along vertebrate chromosomes is highly flexible.
Keywords:CpG Islands, DNA Replication, G-Quadruplexes, Genetic Polymorphism, Genome, HeLa Cells, K562 Cells, Replication Origin, Reproducibility of Results, Single Nucleotide Polymorphism, Species Specificity, Animals, Chickens, Mice
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press (U.K.)
Volume:47
Number:10
Page Range:5114-5125
Date:4 June 2019
Official Publication:https://doi.org/10.1093/nar/gkz182
PubMed:View item in PubMed

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