Adaptive Evolution Of Hox Genes In Cetaceans And The Relationship With The Body Plan Development

Cetaceans, including whales, dolphins, and porpoises, are an exceptional group of mammals which secondly returned to water approximately 53 million years ago (Ma). Transition from land to water and adaptive to full aquatic habitats make cetaceans remarkable and evolutionarily significant. Along with enormous changes in cetacean's body plan and adaptive radiation in waters around the world, cetaceans finally developed multiple species which can be subdivided into two suborders Odontoceti and Mysticeti. In order to adapt to the marine environment, cetacean formed unique anatomical structure. Their neck is short and in some species cervical vertebrae are fused in different degree. All extant cetaceans lack hindlimbs and forelimbs have evolved into paddle-shaped flippers. Cetaceans have a horizontal tail fluke which is its single mode of propulsion under the water. More importantly, cetacean body is streamlined which minimizes the resistance of the water. All these changes make cetaceans adaptive to fully aquatic habitat, but the molecular mechanism for these changes is enigmatic. Hox genes play an important role in patterning and morphogenesis of the vertebrate axial skeleton in tetrapod and mutants of Hox genes would result in deformities. So in this study Hox genes were treated as candidate gene for phylogenetic analysis with other sequences downloaded from database. Comparative genomics and bioinformatics methods were used to detect evolutionary pattern of Hox genes at different branches of mammals, especially whether cetacean Hox genes were subject to positive selection or purify selection. Secondly, to explore whether evolutionary patterns of Hox genes is consistent with the changes of the body axis in cetaceans. We also carried out experimental verification in the representative species of cetacean. In this study, we used the above methods to elaborate the development mechanisms of cetacean's body axis at the molecular level.Through analysis of 26 Hox genes in mammals, the lineage-specific selection test showed that ? (dN/ds) values along most examined cetacean lineages were less than 1, suggesting that functional constraint have effect on Hox genes in cetacean. The results showed that only five genes (HoxA2, HoxA3, HoxB3, HoxB8 and HoxD12) were under positive selection. The physical and chemical properties of positively selected sites detected in these five genes changed greatly, which could be taken as additional evidence of positive selection. Positive selection at the HoxA2, HoxA3 and HoxB3 may be associated with shortened neck in cetaceans. HoxB8 and HoxD12 being under Darwin selection in cetaceans may be correlated to dramatic change of forelimb, including digit decreased and the number of phalanx increased. The results of sliding window analysis for HoxD12 showed that positively selected sites located outside homeobox region. Besides, the homeobox region was more conservative as said before. Our study provided new insights into understanding the molecular mechanisms of development of cetacean body plan and another opportunity for further studies.