Exploring the diversity of AVPR2 in Primates and its evolutionary implications

Area of Science:

• Evolutionary biology
• Genomics
• Primate physiology

Background:

• The arginine vasopressin receptor 2 (AVPR2) is crucial for water homeostasis, regulated by the neurohormone AVP.
• AVPR2 variants can lead to conditions like congenital nephrogenic diabetes insipidus (cNDI), characterized by excessive water loss.

Purpose of the Study:

• Investigate AVPR2 variants across primate taxa to understand evolutionary adaptations.
• Identify functional sites and molecular interactions potentially influenced by selective pressures.

Main Methods:

• Comparative genomic analysis of AVPR2 sequences in diverse primate groups.
• Identification of positively selected sites and co-evolving residues.
• Analysis of protein domains, including SH3-binding motifs, and their conservation.

Main Results:

• Positive selection identified at three AVPR2 sites (190, 250, 346); variation at position 250 is linked to human cNDI.
• Thirteen additional functional sites associated with cNDI were identified.
• SH3-binding motifs were found in AVPR2, with variations across primate clades suggesting adaptive roles.
• Co-evolutionary relationships were observed between AVPR2 and molecules in the same signaling pathway (AVP, AQP2).
• Distinct co-evolving sequences in Platyrrhini and Catarrhini suggest varied selective pressures, potentially involving glucocorticoid hormones.

Conclusions:

• AVPR2 exhibits adaptive evolution in primates, with specific variants potentially influencing water balance and physiological responses.
• The identified functional sites and co-evolutionary patterns highlight the complex adaptive landscape of AVPR2 signaling.
• Further research is needed to fully elucidate the functional and adaptive significance of these primate-specific AVPR2 variations.