Evolutionary analysis of gene ages across TADs associates chromatin topology with whole-genome duplications

Caelinn James, Marco Trevisan-Herraz, David Juan, Daniel Rico*

*Corresponding author for this work

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Topologically associated domains (TADs) are interaction subnetworks of chromosomal regions in 3D genomes. TAD boundaries frequently coincide with genome breaks while boundary deletion is under negative selection, suggesting that TADs may facilitate genome rearrangements and evolution. We show that genes co-localize by evolutionary age in humans and mice, resulting in TADs having different proportions of younger and older genes. We observe a major transition in the age co-localization patterns between the genes born during vertebrate whole-genome duplications (WGDs) or before and those born afterward. We also find that genes recently duplicated in primates and rodents are more frequently essential when they are located in old-enriched TADs and interact with genes that last duplicated during the WGD. Therefore, the evolutionary relevance of recent genes may increase when located in TADs with established regulatory networks. Our data suggest that TADs could play a role in organizing ancestral functions and evolutionary novelty.

Original languageEnglish
Article number113895
JournalCell Reports
Issue number4
Early online date21 Mar 2024
Publication statusPrint publication - 23 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors


  • chromatin
  • CP: Genomics
  • CP: Molecular biology
  • essentiality
  • evolution
  • gene age
  • gene birth
  • genome architecture
  • insulation
  • paralogs
  • TADs
  • whole-genome duplication


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