Decay of TRPV3 as the genomic trace of epidermal structure changes in the land-to-sea transition of mammals

Abstract

The epidermis plays an indispensable barrier function in animals. Some species have evolved unique epidermal structures to adapt to different environments. Aquatic and semi-aquatic mammals (cetaceans, manatees, and hippopotamus) are good models to study the evolution of epidermal structures because of their exceptionally thickened stratum spinosum, the lack of stratum granulosum, and the parakeratotic stratum corneum. This study aimed to analyze an upstream regulatory gene transient receptor potential cation channel, subfamily V, member 3 (TRPV3) of epidermal differentiation so as to explore the association between TRPV3 evolution and epidermal changes in mammals. Inactivating mutations were detected in almost all the aquatic cetaceans and several terrestrial mammals. Relaxed selective pressure was examined in the cetacean lineages with inactivated TRPV3, which might contribute to its exceptionally thickened stratum spinosum as the significant thickening of stratum spinosum in TRPV3 knock-out mouse. However, functional TRPV3 may exist in several terrestrial mammals due to their strong purifying selection, although they have "inactivating mutations." Further, for intact sequences, relaxed selective constraints on the TRPV3 gene were also detected in aquatic cetaceans, manatees, and semi-aquatic hippopotamus. However, they had intact TRPV3, suggesting that the accumulation of inactivating mutations might have lagged behind the relaxed selective pressure. The results of this study revealed the decay of TRPV3 being the genomic trace of epidermal development in aquatic and semi-aquatic mammals. They provided insights into convergently evolutionary changes of epidermal structures during the transition from the terrestrial to the aquatic environment.

Keywords: TRPV3; epidermal structure; inactivating mutations; land‐to‐sea transition; mammals; relaxed selective pressure.

FIGURE 1

Inactivating mutations were detected in TRPV3 of almost all the cetaceans. Relaxed selective constraints on the TRPV3 gene were convergently detected in three clades (cetaceans, manatees, and hippopotamus) with similar epidermis structure, such as parakeratotic stratum corneum, loss of stratum granulosum, and thickened stratum spinosum. These results suggested that the decay of TRPV3 might be the genomic trace of epidermal structure changes in the land‐to‐sea transition of mammals

FIGURE 2

Phylogenetic tree of TRPV3. Using 142 mammalian TRPV3 coding sequences as materials, the phylogenetic tree was reconstructed by the maximum‐likelihood (ML) method using IQ‐TREE. Inconsistencies were found in the clades highlighted in brown when comparing the species tree. The bootstrap values of 78% of nodes were >0.70, which suggested that the TRPV3 gene tree was well supported

FIGURE 3

Inactivating mutations of TRPV3 in multiple mammalian lineages. Left: Phylogeny of 142 placental mammals, in which red font represents species with inactivating mutations and under the relaxed selection pressure of TRPV3, while blue font represents species with inactivating mutations but not under the relaxed selection pressure of TRPV3. The red solid circle represents species (cetaceans, manatees, and hippopotamus) under the relaxed selection pressure of TRPV3 in the placental mammal range. Right: The intact TRPV3 gene model is visualized at the top, superimposed with multiple specific inactivated mutations. Different colors represent different types of mutations. The inactivating mutations were validated by SRA reads and PCR amplification reaction. The alignments of reads are highlighted with gray background, and each inactivating mutation corresponds to a serial number. Sequences in red font represent the mutated sites, while sequences in blue font represent the sequences of humans used as a reference. Notably, the deletions of 3 and 6 bp cover 11 toothed whales, including common bottlenose dolphin Tursiops truncates, Indo‐Pacific bottlenose dolphin Tursiops aduncus, Indo‐Pacific humpback dolphin Sousa chinensis, Pacific white‐sided dolphin Lagenorhynchus obliquidens, long‐finned pilot whale Globicephala melas, killer whale Orcinus orca, harbor porpoise Phocoena phocoena, vaquita Phocoena sinus, Yangtze finless porpoise, beluga whale Delphinapterus leucas, and narwhal Monodon monoceros

FIGURE 4

Results of the selection test. (a) Average evolution rate value (ω) of each branch in mammals. The y‐coordinate represents the value of ω. All ω values of order or superorder are averagely below 0.1 or around 0.1, except the ω of Cetacea near 0.5. Clearly, the amino acid substitution rate in cetaceans was much higher than that in other mammalian groups, suggesting the relaxed selection pressure of cetaceans. (b) Evolution rate value (ω) of species with intact TRPV3 but changed epidermal structure. The y‐coordinate represents the value of ω. The ω of terrestrial mammals (background species) is represented by a gray curve. The ω of species with intact TRPV3 but changed epidermal structure (tested species) is represented by a column. The asterisk represents a significantly improved ω value for the tested species compared with the ω of background species. This indicated that some aquatic or semi‐aquatic mammals (cetaceans, manatees, and hippopotamus) were under relaxed selection pressure, although their sequences of TRPV3 were intact