Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci

Science. 2014 Nov 21;346(6212):1004-6. doi: 10.1126/science.1257493.


Hox genes are required during the morphogenesis of both vertebrate digits and external genitals. We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal. We propose that this convergent regulatory evolution was triggered by the preexistence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Enhancer Elements, Genetic
  • Evolution, Molecular*
  • Extremities
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox*
  • Genetic Loci / genetics*
  • Genetic Pleiotropy*
  • Genitalia / growth & development
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Morphogenesis / genetics*
  • Multigene Family
  • Promoter Regions, Genetic
  • Transcription, Genetic
  • Vertebrates / genetics
  • Vertebrates / growth & development*


  • Homeodomain Proteins
  • homeobox protein HOXA13
  • HoxA protein