A novel enhancer near the Pitx1 gene influences development and evolution of pelvic appendages in vertebrates

Elife. 2018 Nov 30:7:e38555. doi: 10.7554/eLife.38555.

Abstract

Vertebrate pelvic reduction is a classic example of repeated evolution. Recurrent loss of pelvic appendages in sticklebacks has previously been linked to natural mutations in a pelvic enhancer that maps upstream of Pitx1. The sequence of this upstream PelA enhancer is not conserved to mammals, so we have surveyed a large region surrounding the mouse Pitx1 gene for other possible hind limb control sequences. Here we identify a new pelvic enhancer, PelB, that maps downstream rather than upstream of Pitx1. PelB drives expression in the posterior portion of the developing hind limb, and deleting the sequence from mice alters the size of several hind limb structures. PelB sequences are broadly conserved from fish to mammals. A wild stickleback population lacking the pelvis has an insertion/deletion mutation that disrupts the structure and function of PelB, suggesting that changes in this ancient enhancer contribute to evolutionary modification of pelvic appendages in nature.

Keywords: developmental biology; enhancer; evolution; evolutionary biology; hindlimb development; mouse; pelvis; pitx1; stickleback.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Biological Evolution*
  • Chromosomes, Artificial, Bacterial / metabolism
  • Conserved Sequence
  • Enhancer Elements, Genetic*
  • Fishes / embryology
  • Gene Expression Regulation, Developmental
  • Genetic Loci
  • Genome
  • Hindlimb / growth & development
  • Lizards / embryology
  • Mice
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • Pelvis / growth & development*
  • Sequence Deletion
  • Vertebrates / genetics*
  • Vertebrates / growth & development*

Substances

  • Paired Box Transcription Factors
  • homeobox protein PITX1