Evolutionary Insights into the Relationship of Frogs, Salamanders, and Caecilians and Their Adaptive Traits, with an Emphasis on Salamander Regeneration and Longevity

SIMPLE SUMMARY: Amphibians have unique traits, such as regeneration and longevity in salamanders, frequent vocalization in frogs, and degenerative vision in caecilians. The genetic basis of these traits is not well understood. This study aimed to investigate the genetic changes underlying these unique traits, especially salamanders’ regeneration and longevity, by comparing the genes of amphibians to other vertebrates. I found that salamander genomes have undergone accelerated adaptive evolution, especially for development-related genes. Several salamanders’ genes are under positive selection and/or share mutations with other long-lived and regenerative vertebrates, suggesting that these genes are important for these unique traits. This study could help us to better understand the mechanisms of regeneration and aging, which could lead to the development of new ways to improve human health and well-being. ABSTRACT: The extant amphibians have developed uncanny abilities to adapt to their environment. I compared the genes of amphibians to those of other vertebrates to investigate the genetic changes underlying their unique traits, especially salamanders’ regeneration and longevity. Using the well-supported Batrachia tree, I found that salamander genomes have undergone accelerated adaptive evolution, especially for development-related genes. The group-based comparison showed that several genes are under positive selection, rapid evolution, and unexpected parallel evolution with traits shared by distantly related species, such as the tail-regenerative lizard and the longer-lived naked mole rat. The genes, such as EEF1E1, PAFAH1B1, and OGFR, may be involved in salamander regeneration, as they are involved in the apoptotic process, blastema formation, and cell proliferation, respectively. The genes PCNA and SIRT1 may be involved in extending lifespan, as they are involved in DNA repair and histone modification, respectively. Some genes, such as PCNA and OGFR, have dual roles in regeneration and aging, which suggests that these two processes are interconnected. My experiment validated the time course differential expression pattern of SERPINI1 and OGFR, two genes that have evolved in parallel in salamanders and lizards during the regeneration process of salamander limbs. In addition, I found several candidate genes responsible for frogs’ frequent vocalization and caecilians’ degenerative vision. This study provides much-needed insights into the processes of regeneration and aging, and the discovery of the critical genes paves the way for further functional analysis, which could open up new avenues for exploiting the genetic potential of humans and improving human well-being.