Relaxed constraint and functional divergence of PGR

To resolve existing conflicting data on progesterone receptor gene (PGR) evolution, the study assembled a dataset of 119 Eutherian PGRs and used a suite of maximum likelihood-based methods to characterize the strength and direction of selection acting on PGR. The result shows that PGR evolved rapidly in the human 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