Hair is one of the most distinguishing characteristics of mammals and has many important biological functions.Cetaceans,which evolved from terrestrial mammals,have evolved a series of adaptations to an aquatic environment and are therefore of evolutionary significance.Yet the molecular mechanism for their fully aquatic adaptations is not well explored.Here,in order to provide insights into the evolution of hair loss during the transition from land to water,we investigated and compared two essential and indispensable regulators of hair follicle development and hair follicle cycling,Hr and FGF5 genes,of representative cetaceans and their terrestrial relatives.Sequence characterizations and evolutionary analyses provided evidences for the loss of function of Hr genes in cetaceans,which might support absent dependence on hair as a result of fully adaptation to the aquatic habitat.By contrast,positive selection acting on FGF5 genes was found in cetaceans and a series of positively selected amino acid residues were detected.It was suggested that positive selection acting on FGF5 genes might have promoted the termination of hair growth and the early entry into the catagen of the hair follicle cycling.Consequently,the hair follicles were disrupted and the hair was completely lost due to the loss of function of Hr genes in cetaceans,which suggested that cetaceans have evolved an effective and complex mechanism for hair loss.In addition to provide interesting insights into the mechanism for hair loss during transition from land to water,this study could also contribute to the current knowledge of the function of hairless (Hr) gene and FGF5 genes in hair follicle development and hair follicle cycling.