Convergent evolution of endometrial prolactin expression in primates, mice, and elephants through the independent recruitment of transposable elements

Deena Emera, Claudio Casola, Vincent J. Lynch, Derek E. Wildman, Dalen Agnew, Günter P. Wagner

Research output: Contribution to journalArticlepeer-review


Prolactin (PRL) is a multifunctional signaling molecule best known for its role in regulating lactation in mammals. Systemic PRL is produced by the anterior pituitary, but extrapituitary PRL has also been detected in many tissues including the human endometrium. Prolactin is essential for pregnancy in rodents and one of the most dramatically induced genes in the endometrium during human pregnancy. The promoter for human endometrial Prl is located about 5.8 kb upstream of the pituitary promoter and is derived from a transposable element called MER39. Although it has been shown that prolactin is expressed in the pregnant endometrium of a few mammals other than humans, MER39 has been described as primate specific. Thus, in an effort to understand mechanisms of prolactin regulatory evolution, we sought to determine how uterine prolactin is transcribed in species that lack MER39. Using a variety of complementary strategies, including reverse transcriptase-polymerase chain reaction, 5# rapid amplification of cDNA ends, and whole-Transcriptome sequencing, we show that endometrial Prl expression is not a shared character of all placental mammals, as it is not expressed in rabbits, pigs, dogs, or armadillos. We show that in primates, mice, and elephants, prolactin mRNA is transcribed in the pregnant endometrium from alternative promoters, different from the pituitary promoter and different from each other. Moreover, we demonstrate that the spider monkey promoter derives from the long terminal repeat (LTR) element MER39 as in humans, the mouse promoter derives from the LTR element MER77, and the elephant promoter derives from the lineage-specific LINE retrotransposon L1-2 LA. We also find surprising variation of transcriptional start sites within these transposable elements and of Prl splice variants, suggesting a high degree of flexibility in the promoter architecture even among closely related species. Finally, the three groups shown here to express endometrial prolactin-The higher primates, the rodents, and the elephant-represent three of the four lineages that showed adaptive evolution of the Prl gene in an earlier study (Wallis M. 2000. Episodic evolution of protein hormones: molecular evolution of pituitary prolactin. J Mol Evol. 50:465-473), which supports our findings and suggests that the selective forces responsible for accelerated Prl evolution were in the endometrium. This is the first reported case of convergent evolution of gene expression through the independent recruitment of different transposable elements, highlighting the importance of transposable elements in gene regulatory, and potentially adaptive, evolution.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalMolecular biology and evolution
Issue number1
StatePublished - Jan 2012
Externally publishedYes


  • Alternative promoters
  • Convergent evolution
  • Endometrial prolactin
  • Transposable elements

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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