3D chromatin remodelling in the germ line modulates genome evolutionary plasticity

Lucía Álvarez-González, Frances Burden, Dadakhalandar Doddamani, Roberto Malinverni, Emma Leach, Cristina Marín-García, Laia Marín-Gual, Albert Gubern, Covadonga Vara, Andreu Paytuví-Gallart, Marcus Buschbeck, Peter J I Ellis, Marta Farré, Aurora Ruiz-Herrera

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The role of genome folding in the heritability and evolvability of structural variations is not well understood. Here the authors investigate the impact of the three-dimensional genome topology of germ cells in the formation and transmission of gross structural genomic changes detected from comparing whole-genome sequences of 14 rodent species.

Chromosome folding has profound impacts on gene regulation, whose evolutionary consequences are far from being understood. Here we explore the relationship between 3D chromatin remodelling in mouse germ cells and evolutionary changes in genome structure. Using a comprehensive integrative computational analysis, we (i) reconstruct seven ancestral rodent genomes analysing whole-genome sequences of 14 species representatives of the major phylogroups, (ii) detect lineage-specific chromosome rearrangements and (iii) identify the dynamics of the structural and epigenetic properties of evolutionary breakpoint regions (EBRs) throughout mouse spermatogenesis. Our results show that EBRs are devoid of programmed meiotic DNA double-strand breaks (DSBs) and meiotic cohesins in primary spermatocytes, but are associated in post-meiotic cells with sites of DNA damage and functional long-range interaction regions that recapitulate ancestral chromosomal configurations. Overall, we propose a model that integrates evolutionary genome reshuffling with DNA damage response mechanisms and the dynamic spatial genome organisation of germ cells.

Original languageEnglish
Article number2608
Pages (from-to)2608
Number of pages15
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - 11 May 2022

Keywords

  • CELLS
  • CHROMOSOMES
  • EXPRESSION
  • INSIGHTS
  • PRINCIPLES
  • REGIONS
  • REVEALS

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