Molecular evolutionary insights from PRLR in mammals

Area of Science:

• Evolutionary biology
• Molecular endocrinology
• Genomics

Background:

• Prolactin (PRL) is a key neurohormone regulating mammalian physiology and reproduction.
• The prolactin receptor (PRLR) mediates PRL's diverse cellular effects.
• The intracellular domain of PRLR (PRLR-ICD) plays a role in gene expression modulation.

Purpose of the Study:

• To investigate the evolutionary conservation and divergence of PRLR-ICD functional motifs.
• To identify selection pressures acting on PRLR-ICD across mammalian evolution.
• To explore potential pre-adaptive roles of PRLR-ICD in primate evolution.

Main Methods:

• Comparative genomics analysis of PRLR-ICD sequences across diverse mammalian groups.
• Phylogenetic analysis to detect signatures of natural selection (purifying and relaxed).
• Identification of conserved and novel functional motifs within the PRLR-ICD.

Main Results:

• PRLR-ICD exhibits conserved functional elements across Mammalia, maintained by purifying selection.
• Evidence of relaxed selection on specific PRLR-ICD residues, particularly in primates (Simiiformes).
• Identification of potential novel functional motifs (e.g., YLDP) in primate PRLR-ICD.

Conclusions:

• The core functions of the PRL-PRLR system are conserved across mammals due to strong purifying selection on PRLR-ICD.
• Relaxed selection and novel motifs in primate PRLR-ICD may reflect adaptations for specific phenotypes.
• These primate-specific changes likely do not impact fundamental mammalian PRLR functions.