Molecular evolutionary insights from PRLR in mammals

• Published in: General and comparative endocrinology Vol. 309; p. 113791
• Main Authors: Paré, Pamela, Reales, Guillermo, Paixão-Côrtes, Vanessa R., Vargas-Pinilla, Pedro, Viscardi, Lucas Henriques, Fam, Bibiana, Pissinatti, Alcides, Santos, Fabrício R., Bortolini, Maria Cátira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2021
• Subjects: Animals; Evolution, Molecular; Female; Intracellular signal; Mammals; Mammals - genetics; Mammals - metabolism; Molecular evolution; Pituitary Gland - metabolism; Prolactin - metabolism; Prolactin receptor; Receptors, Prolactin - genetics; Receptors, Prolactin - metabolism; Molecular evolution; Prolactin receptor; Mammals; Intracellular signal
• ISSN: 0016-6480; 1095-6840; 1095-6840
• DOI: 10.1016/j.ygcen.2021.113791

•PRLR-ICD variability and its structural features were selectively maintained.•Motif sequences were strongly maintained under purifying selection.•Adaptive or pre-adaptive elements may have emerged in Simiiformes: YLDP 318–321, Y283, and Y290. Prolactin (PRL) is a pleiotropic neurohormone secreted by the mammalian pituitary gland into the blood, thus reaching many tissues and organs beyond the brain. PRL binds to its receptor, PRLR, eliciting a molecular signaling cascade. This system modulates essential mammalian behaviors and promotes notable modifications in the reproductive female tissues and organs. Here, we explore how the intracellular domain of PRLR (PRLR-ICD) modulates the expression of the PRLR gene. Despite differences in the reproductive strategies between eutherian and metatherian mammals, there is no clear distinction between PRLR-ICD functional motifs. However, we found selection signatures that showed differences between groups, with many conserved functional elements strongly maintained through purifying selection across the class Mammalia. We observed a few residues under relaxed selection, the levels of which were more pronounced in Eutheria and particularly striking in primates (Simiiformes), which could represent a pre-adaptive genetic element protected from purifying selection. Alternative, new motifs, such as YLDP (318–321) and others with residues Y283 and Y290, may already be functional. These motifs would have been co-opted in primates as part of a complex genetic repertoire related to some derived adaptive phenotypes, but these changes would have no impact on the primordial functions that characterize the mammals as a whole and that are related to the PRL-PRLR system.