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Nature Study Finds Digits Evolved by Reusing Ancestral Cloacal Regulatory DNA

CRISPR evidence links a conserved 5DOM switch to Hoxd13 control that shifted from the fish cloaca to limb tips in tetrapods.

Overview

  • An international team from the University of Geneva, EPFL, Collège de France, Harvard and the University of Chicago reports the findings in Nature.
  • Comparative genomics pinpointed a conserved non-coding landscape called 5DOM that regulates Hox genes tied to distal limb patterning.
  • Deleting 5DOM in mice disrupted finger and toe development as well as external genital formation, demonstrating its regulatory role.
  • In zebrafish, 5DOM loss erased Hoxd13 activity in the cloaca without altering fins, with reporter assays showing species-specific activation.
  • The authors conclude that digit anatomy arose through evolutionary co-option of regulatory DNA conserved for roughly 350–380 million years, a model with implications for limb malformations and regenerative research.