Meeting Abstract

26.10  Monday, Jan. 5  Domestication and adaptation of a transposable element in to a tissue-specific enhancer of prolactin (PRL) was an essential step in the origin of pregnancy in placental mammals LYNCH, Vincent/J*; WAGNER, Gunter/P; Yale University; Yale University vincent.j.lynch@yale.edu

The evolution of gene regulation, particularly through cis-regulatory element and transcription factor change, is widely thought to be the molecular basis developmental evolution. Classic early studies suggested that repetitive elements may have played an important role in reorganizing genomes and regulatory networks promoting the origin of novel gene regulatory links, but clear examples of transposable elements conferring positive effects on gene regulation are still rare. Here, were show that a transposable element (MER20) integrated upstream of prolactin (PRL), a multifunctional gene essential for implantation and pregnancy, in the stem-lineage of placental mammals and generated a novel tissue-specific enhancer that drives PRL expression in the uterus and placenta. Molecular evolutionary analysis of the MER20-derived enhancer indicates that some binding sites are ancient and likely were function upon insertion while other binding-sites for several transcription factors that regulate PRL have statistical signatures of adaptive evolution coincident with the origin of PRL expression in the female reproductive tract. Remarkably, many of the nucleotide substitutions in the MER20-derived PRL enhancer mutated pre binding-sites into consensus binding sites for transcription factors that regulate uterine PRL expression. These results show that transposable elements can contribute to evolutionarily important changes in gene regulation, potentially generating novel regulons and facilitating developmental evolution.