3.1 Phylogenetic relationship of TMPRSS2 among 164 vertebrates
A phylogenetic tree consisting of 164 vertebrate species were constructed using the whole protein sequence of TMPRSS2 to evaluate the homology across species (Fig S1). The tree showed four main clades. The Chondrichthyes TMPRSS2 formed the most basal branch, followed bt the Osteichthyes and Amphibia TMPRSS2 clades. The TMPRSS2 of Mammalia, Reptilia, and Aves formed the last clade, in which the Mammalia TMPRSS2 formed the sister cluster with that of Reptilia and Aves. The phylogenetic relationship of TMPRSS2 among different species was highly consistent with the evolutionary relationships at the species level, as well as the genetic distance (Table S2). We further confirmed the start and end positions of three main conserved domain regions of TMPRSS2 to focus on this analysis in more conserved functional regions (Fig 1, Fig S2, Fig S3). The overall structure of the tree built with the conserved region was well in line with the tree constructed using the complete sequences with only a few detailed differences. We further built a phylogenetic tree of TMPRSS2 using selected species that are closer to humans (Fig 2). Important livestock, like pig, sheep and cattle, was closely clustered with cat, dog, and pangolin, which are shown to be effected by SARS-CoV-2. The horse was also placed with the human. In addition, rat, mouse and hamster shared the same clade with human. Bird, reptile, amphibian and fish were not found to be mixed into the susceptible animals.