Accelerated Evolution of Limb-Related Gene in the Common Ancestor of Cetaceans and Ruminants (Cetruminantia).

Reduced numbers of carpal and tarsal bones (wrist and ankle joints) are extensively observed in the clade of Cetacea and Ruminantia (Cetruminantia). () is one of the important genes required for limb development in mammals. Mutations in can lead to defects in particular bones of limbs, including carpus and tarsus. To test whether evolutionary changes in underlie the loss of these bones in Cetruminantia, we sequenced and analyzed coding sequences and compared them with other 5' and genes in a taxonomic coverage of Cetacea, Ruminantia and other mammalian relatives. Statistical tests on the 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 5' and genes do not show this same evolutionary pattern, but instead display a highly conserved pattern of evolution in this lineage. Accelerated evolution of , but not other 5' and 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 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 adaptive evolution in cetaceans and ruminants, which could be correlated with limb morphological adaptation.