Fam Bibiana Sampaio de Oliveira, Vargas-Pinilla Pedro, Paré Pâmela, Landau Luane, Viscardi Lucas H, Pissinatti Alcides, Falótico Tiago, Maestri Renan, Bortolini Maria Cátira
Universidade Federal do Rio Grande do Sul, Departamento de Genética, Laboratório de Evolução Humana e Molecular, Porto Alegre, RS, Brazil.
Universidade de São Paulo, Faculdade de Medicina, Departamento de Bioquímica e Imunologia, Ribeirão Preto, SP, Brazil.
Genet Mol Biol. 2023 Nov 3;46(3):e20230045. doi: 10.1590/1678-4685-GMB-2023-0045. eCollection 2023.
The current study focuses on the investigation of AVPR2 (VTR2C) protein-coupled receptor variants specific to different primate taxa. AVPR2 is activated by the neurohormone AVP, which modulates physiological processes, including water homeostasis. Our findings reveal positive selection at three AVPR2 sites at positions 190, 250, and 346. Variation at position 250 is associated with human Congenital Nephrogenic Diabetes Insipidus (cNDI), a condition characterized by excessive water loss. Other 13 functional sites with potential adaptive relevance include positions 185, 202, 204, and 252 associated with cNDI. We identified SH3-binding motifs in AVPR2's ICL3 and N-terminus domains, with some losses observed in clades of Cercopithecidae, Callitrichinae, and Atelidae. SH3-binding motifs are crucial in regulating cellular physiology, indicating that the differences may be adaptive. Co-evolution was found between AVPR2 residues and those in the AVP signal peptide/Neurophysin-2 and AQP2, other molecules in the same signaling cascade. No significant correlation was found between these Primates' taxon-specific variants and the bioclimatic variables of the areas where they live. Distinct co-evolving amino acid sequences in functional sites were found in Platyrrhini and Catarrhini, which may have adaptive implications involving glucocorticoid hormones, suggesting varied selective pressures. Further studies are required to confirm these results.
当前的研究聚焦于对不同灵长类分类群特有的AVPR2（VTR2C）蛋白偶联受体变体的调查。AVPR2由神经激素抗利尿激素（AVP）激活，AVP可调节包括水平衡在内的生理过程。我们的研究结果显示，在第190、250和346位的三个AVPR2位点存在正选择。第250位的变异与人类先天性肾性尿崩症（cNDI）相关，这是一种以水分过度流失为特征的病症。其他13个具有潜在适应性关联的功能位点包括与cNDI相关的第185、202、204和252位。我们在AVPR2的ICL3和N端结构域中鉴定出SH3结合基序，在猕猴科、狨猴亚科和蛛猴科的进化枝中观察到了一些缺失。SH3结合基序在调节细胞生理方面至关重要，这表明这些差异可能具有适应性。在AVPR2残基与AVP信号肽/神经垂体素-2以及水通道蛋白2（AQP2，同一信号级联中的其他分子）的残基之间发现了协同进化。在这些灵长类动物的分类群特异性变体与它们所生活地区的生物气候变量之间未发现显著相关性。在阔鼻猴类和狭鼻猴类中发现了功能位点中不同的协同进化氨基酸序列，这可能涉及糖皮质激素的适应性影响，表明存在不同的选择压力。需要进一步的研究来证实这些结果。
