Research On The Molecular Evolutionary Mechanism Of Pain Perception In Cetaceans

Pain is caused by the stimulation of nociceptors.The mechanical,thermal,and chemical stimulation of pain receptors is processed into electrical signals.This impulse is transmitted along the nerve fibers to the spinal cord,and then to the brain to produce the sensation of pain.Studies have shown that different species have different pain sensitivity.The naked mole rat(Heterocephalus glaber)and other African rodents are not sensitive to acid or capsaicin,which is related to their long-term low-oxygen underground environment;bats such as Antrozous Pallidus coexist with scorpions and are not sensitive to the toxins produced by scorpions.The amino acid sites of their sodium ion channel have been changed.The insensitivity of these animals to pain represents an adaptation to the environment.Generally speaking,salt causes more pain to animals,but cetaceans live in seawater with high salt content(The salinity is 32%-37%).Field observations of cetaceans are indifferent to pain after being injured.The related reasons have not been reported.At the same time,related studies have shown that several pain-related genes in cetaceans have accelerated their evolution.Therefore,this study selected 31 pain-related genes(SCN9A,SCN10 A,PRDM12,ANO1,CCK,ERK1,ERK2,RUNX1,NGF,NTRK1,CACNA1 G,TRPV1,TRPV4,P2RX3,P2RX4,ASIC1,ASIC3,ASIC4,CA8,GRK2,ARRB2,KCNA1,KCNA2,TRAAK,KCNIP3,KCNJ10,ANO3,OPRM1,OPRL1,OPRK1 and OPRD1)from 43 mammalian species for research,using NCBI and Ortho Ma M and other websites.Find the protein coding sequence of the gene to conduct bioinformatics analysis to explore the molecular evolutionary mechanism of cetacean pain perception.In this study,the branch model was first used for analysis,and it was found that a total of four pain genes(ASIC3,SCN9 A,PRDM12,TRPV4)and one analgesic gene(CA8)detected positive selection signals in the branch lines of cetaceans.Then we used the branch site model to analyze 31 genes,and detected positive selection sites in7 pain genes(ASIC3,ANO1,CCK,SCN9 A,SCN10A,CACNA1 G,P2RX4),among which the pain genes are in cetaceans There is no significant difference in the number of positive selection sites in cetaceous species compared to the number of positive selection sites in non-cetacean species.Positive selection sites were detected in 6analgesic genes(OPRM1,OPRL1,OPRK1,OPRD1,ARRB2,TRAAK),mainly in cetaceans,positive selection sites in cetaceans and positive selection in non-cetaceans There is a significant difference in the number of sites.This also shows that compared with other mammals,cetaceans' analgesic genes are under stronger selective pressure,and these analgesic genes have evolved adaptively in the face of the complex environment of the ocean.Later,the study found that the pain-related gene ASIC4 terminated prematurely in toothed whales and Hawaiian monk seals except sperm whales.The pseudogeneization of the ASIC4 gene may be related to other sensory methods.Then,the specific sites of pain genes in cetaceans were detected to explore the relationship between changes in amino acid sites and decreased pain sensitivity of cetaceans.Through analysis,specific sites were detected in 15 genes of cetacean species,including 7 pain genes(P2RX3,SCN9 A,SCN10A,PRDM12,ASIC3,TRPV1,NGF)and 8 analgesic genes(ANO3,CA8,KCNA1,KCNIP3,GRK2,KCNJ10,OPRD1,OPRK1).The specific sites of some of the genes are located in important functional domains,which also suggests that these specific sites may have an impact on the decreased pain sensitivity of cetaceans.Finally,in order to explore whether there is convergent evolution in species with reduced pain sensitivity(including cetaceans,naked mole rats,and bats),Fasparser software was used to analyze pain-related genes and found that there are five genes(ASIC3,SCN10 A,CCK,OPRL1,ANO3)has detected a convergent site.This also indicates that these genes play a similar role in species with decreased pain sensitivity,and are closely related to decreased pain sensitivity.Combined with the above bioinformatics analysis of cetacean pain-related genes,the molecular evolutionary mechanism of reduced pain sensitivity of cetaceans was explored,which provided a theoretical basis for the study of the adaptive evolutionary mechanism of cetaceans' aquatic life.