Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage

Autoři: Mirna Marinić aff001;  Vincent J. Lynch aff002
Působiště autorů: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL, United States of America aff001;  Department of Biological Sciences, University at Buffalo, SUNY, Buffalo, NY, United States of America aff002
Vyšlo v časopise: Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008666
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008666


The steroid hormone progesterone, acting through the progesterone receptor (PR), a ligand-activated DNA-binding transcription factor, plays an essential role in regulating nearly every aspect of female reproductive biology. While many reproductive traits regulated by PR are conserved in mammals, Catarrhine primates evolved several derived traits including spontaneous decidualization, menstruation, and a divergent (and unknown) parturition signal, suggesting that PR may also have evolved divergent functions in Catarrhines. There is conflicting evidence, however, whether the progesterone receptor gene (PGR) was positively selected in the human lineage. Here we show that PGR evolved rapidly in the human stem-lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology.

Klíčová slova:

Amino acid substitution – Evolutionary rate – Hominins – Luciferase – Multiple alignment calculation – Primates – Progesterone – Sequence alignment


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