Reduced numbers of carpal and tarsal bones (wrist and ankle joints) are extensively observed in the clade of Cetacea and Ruminantia (Cetruminantia). Homebox D11 (Hoxd11) is one of the important genes required for limb development in mammals. Mutations in Hoxd11 can lead to defects in particular bones of limbs, including carpus and tarsus. To test whether evolutionary changes in Hoxd11 underlie the loss of these bones in Cetruminantia, we sequenced and analyzed Hoxd11 coding sequences and compared them with other 59 HoxA and HoxD genes in a taxonomic coverage of Cetacea, Ruminantia and other mammalian relatives. Statistical tests on the Hoxd11 sequences found an accelerated evolution in the common ancestor of cetaceans and ruminants, which coincided with the reduction of carpal and tarsal bones in this clade. Five amino acid substitutions (G222S, G227A, G229S, A240T and G261V) and one amino acid deletion (G254Del) occurred in this lineage. In contrast, other 59 HoxA and HoxD genes do not show this same evolutionary pattern, but instead display a highly conserved pattern of evolution in this lineage. Accelerated evolution of Hoxd11, but not other 59 HoxA and HoxD genes, is probably related to the reduction of the carpal and tarsal bones in Cetruminantia. Moreover, we found two amino acid substitutions (G110S and D223N) in Hoxd11 that are unique to the lineage of Cetacea, which coincided with hindlimb loss in the common ancestor of cetaceans. Our results give molecular evidence of Hoxd11 adaptive evolution in cetaceans and ruminants, which could be correlated with limb morphological adaptation.

Purpose. To report the first complete fox coronavirus (CoV) genome sequence obtained through genome‐wide amplifications and to understand the adaptive evolution of fox CoV. Methods. Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results. Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species‐specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion. The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments.