A novel enhancer near the <i>Pitx1</i> gene influences development and evolution of pelvic appendages in vertebrates.

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 <i>Pitx1</i>. The sequence of this upstream <i>PelA</i> enhancer is not conserved to mammals, so we have surveyed a large region surrounding the mouse <i>Pitx1</i> gene for other possible hind limb control sequences. Here we identify a new pelvic enhancer, <i>PelB</i>, that maps downstream rather than upstream of <i>Pitx1. PelB</i> 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. <i>PelB</i> 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 <i>PelB</i>, suggesting that changes in this ancient enhancer contribute to evolutionary modification of pelvic appendages in nature.