Céspedes Héctor A, Zavala Kattina, Vandewege Michael W, Opazo Juan C
Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.
Gen Comp Endocrinol. 2017 Sep 1;250:85-94. doi: 10.1016/j.ygcen.2017.06.006. Epub 2017 Jun 13.
Evolutionary studies of genes that have been functionally characterized and whose variation has been associated with pathological conditions represent an opportunity to understand the genetic basis of pathologies. α-Adrenoreceptors (ADRA2) are a class of G protein-coupled receptors that regulate several physiological processes including blood pressure, platelet aggregation, insulin secretion, lipolysis, and neurotransmitter release. This gene family has been extensively studied from a molecular/physiological perspective, yet much less is known about its evolutionary history. Accordingly, the goal of this study was to investigate the evolutionary history of α-adrenoreceptors (ADRA2) in vertebrates. Our results show that in addition to the three well-recognized α-adrenoreceptor genes (ADRA2A, ADRA2B and ADRA2C), we recovered a clade that corresponds to the fourth member of the α-adrenoreceptor gene family (ADRA2D). We also recovered a clade that possesses two ADRA2 sequences found in two lamprey species. Furthermore, our results show that mammals and crocodiles are characterized by possessing three α-adrenoreceptor genes, whereas all other vertebrate groups possess the full repertoire of α-adrenoreceptor genes. Among vertebrates ADRA2D seems to be a dispensable gene, as it was lost two independent times during the evolutionary history of the group. Additionally, we found that most examined species possess the most common alleles described for humans; however, there are cases in which non-human mammals possess the alternative variant. Finally, transcript abundance profiles revealed that during the early evolutionary history of gnathostomes, the expression of ADRA2D in different taxonomic groups became specialized to different tissues, but in the ancestor of sarcopterygians this specialization would have been lost.
对已进行功能表征且其变异与病理状况相关的基因进行进化研究，为理解病理学的遗传基础提供了契机。α-肾上腺素能受体（ADRA2）是一类G蛋白偶联受体，可调节多种生理过程，包括血压、血小板聚集、胰岛素分泌、脂肪分解和神经递质释放。该基因家族已从分子/生理学角度进行了广泛研究，但其进化历史却知之甚少。因此，本研究的目的是调查脊椎动物中α-肾上腺素能受体（ADRA2）的进化历史。我们的研究结果表明，除了三个广为人知的α-肾上腺素能受体基因（ADRA2A、ADRA2B和ADRA2C）外，我们还发现了一个与α-肾上腺素能受体基因家族的第四个成员（ADRA2D）相对应的进化枝。我们还发现了一个进化枝，其中包含在两种七鳃鳗物种中发现的两个ADRA2序列。此外，我们的研究结果表明，哺乳动物和鳄鱼的特征是拥有三个α-肾上腺素能受体基因，而所有其他脊椎动物类群则拥有完整的α-肾上腺素能受体基因库。在脊椎动物中，ADRA2D似乎是一个可有可无的基因，因为它在该类群的进化历史中独立丢失了两次。此外，我们发现大多数被检测的物种拥有人类描述的最常见等位基因；然而，在某些情况下，非人类哺乳动物拥有替代变体。最后，转录本丰度谱显示，在有颌类动物的早期进化历史中，ADRA2D在不同分类群中的表达专门针对不同组织，但在肉鳍鱼类的祖先中，这种专门化已经丧失。
