Germline Structural Variations Are Preferential Sites of DNA Replication Timing Plasticity during Development.


Journal

Genome biology and evolution
ISSN: 1759-6653
Titre abrégé: Genome Biol Evol
Pays: England
ID NLM: 101509707

Informations de publication

Date de publication:
01 06 2019
Historique:
accepted: 02 05 2019
pubmed: 12 5 2019
medline: 5 11 2019
entrez: 12 5 2019
Statut: ppublish

Résumé

The DNA replication timing program is modulated throughout development and is also one of the main factors influencing the distribution of mutation rates across the genome. However, the relationship between the mutagenic influence of replication timing and its developmental plasticity remains unexplored. Here, we studied the distribution of copy number variations (CNVs) and single nucleotide polymorphisms across the zebrafish genome in relation to changes in DNA replication timing during embryonic development in this model vertebrate species. We show that CNV sites exhibit strong replication timing plasticity during development, replicating significantly early during early development but significantly late during more advanced developmental stages. Reciprocally, genomic regions that changed their replication timing during development contained a higher proportion of CNVs than developmentally constant regions. Developmentally plastic CNV sites, in particular those that become delayed in their replication timing, were enriched for the clustered protocadherins, a set of genes important for neuronal development that have undergone extensive genetic and epigenetic diversification during zebrafish evolution. In contrast, single nucleotide polymorphism sites replicated consistently early throughout embryonic development, highlighting a unique aspect of the zebrafish genome. Our results uncover a hitherto unrecognized interface between development and evolution.

Identifiants

pubmed: 31076752
pii: 5487996
doi: 10.1093/gbe/evz098
pmc: PMC6582765
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1663-1678

Subventions

Organisme : NIGMS NIH HHS
ID : DP2 GM123495
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121703
Pays : United States

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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Auteurs

Michelle L Hulke (ML)

Department of Molecular Biology and Genetics, Cornell University.

Joseph C Siefert (JC)

Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation.
Department of Cell Biology, University of Oklahoma Health Sciences Center.

Christopher L Sansam (CL)

Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation.
Department of Cell Biology, University of Oklahoma Health Sciences Center.

Amnon Koren (A)

Department of Molecular Biology and Genetics, Cornell University.

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