Rubbing Salt in the Wound: Molecular Evolutionary Analysis of Pain-Related Genes Reveals the Pain Adaptation of Cetaceans in Seawater

• Published in: Animals
• Main Authors: Ding, Xiaoyue, Yu, Fangfang, He, Xiaofang, Xu, Shixia, Yang, Guang, Ren, Wenhua
• Format: Text
• Language: English
• Published: MDPI 2022
• Subjects: Article; Physeter macrocephalus; toothed whales
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774174/; https://doi.org/10.3390/ani12243571

SIMPLE SUMMARY: Cetaceans are aquatic mammals that evolved a series of specializations for life in an aquatic habitat, such as lack of distal hindlimbs, loss of hair, and derivation of echolocation. Notably, in the face of high salinity of seawater, the molecular mechanism of adaptation to pain in cetacean is still unclear. In this study, we performed molecular evolutionary analyses of genes related to pain perception (pain) and pain relief (analgesia) in selected representatives of mammals to explore the molecular mechanisms of pain adaptation in cetaceans to ‘rubbing salt in the wound’. Relaxed selection, positive selection, and convergent and specific amino acid substitutions were identified within cetacean’s pain-related genes, showing that the adaptation of mammals to a seawater environment might also include molecular evolution towards greater sensitivity to pain and more effective analgesia. Our study could have implications for diagnosis and treatment of human pain. ABSTRACT: Pain, usually caused by a strong or disruptive stimulus, is an unpleasant sensation that serves as a warning to organisms. To adapt to extreme environments, some terrestrial animals have evolved to be inherently insensitive to pain. Cetaceans are known as supposedly indifferent to pain from soft tissue injury representatives of marine mammals. However, the molecular mechanisms that explain how cetaceans are adapted to pain in response to seawater environment remain unclear. Here, we performed a molecular evolutionary analysis of pain-related genes in selected representatives of cetaceans. ASIC4 gene was identified to be pseudogenized in all odontocetes (toothed whales) except from Physeter macrocephalus (sperm whales), and relaxed selection of this gene was detected in toothed whales with pseudogenized ASIC4. In addition, positive selection was detected in pain perception (i.e., ASIC3, ANO1, CCK, and SCN9A) and analgesia (i.e., ASIC3, ANO1, CCK, and SCN9A) genes among the examined cetaceans. In this study, potential convergent amino ...