Evolutionary Changes In The Hox Gene And Related Regulatory Factors Are Studied In Mammalian Phenotypic Modification

Axial skeleton and appendages play pivotal roles in locomotion, bracing and body protection. The formation of axial skeleton and appendages during the evolutionary process provides guarantee for evolutionary radiations and adaptation to diverse environment among species. As the most differentiated group, mammals have subjected to significant phenotypic changes during the process of mammalian evolution. However, the genetics mechanism leading to the morphology change has not resolved up to now. Hox families have been receiving much concern, during the embryonic development, for their indispensable function specifying anterior-posterior axis morphological characteristics.In the present research, we have conducted bioinformatics and comparative genomics analysis from three aspects (Hox cluster organization, Hox coding sequence and relevant regulatory factors evolution analysis) to explore the important role of Hox gene evolution changes on the phenotypic modification of mammalian axial skeleton and appendages during the adaptation into different habitats. Our results have showed an obvious increase of LINEs in bat Hoxa and afrotheria Hoxb cluster respectively and changes of the repetitive sequence density in marine mammal Hoxc and Hoxd clusters, which suggest a modification of relevant Hox gene expression and future leading to phenotypic changes of these lineages above-mentioned. Investigatation on Hox genes has shown that some Hox genes (Hoxa11, Hoxd9, Hoxc4, Hoxc10, Hoxd10, and Hoxd12) have subjected to accelerated evolution or positive selection in some lineages or species and lineage-specific mutations with radical amino acid property changes (Hoxa:Hoxa3, Hoxa6; Hoxb:Hoxb9; Hoxc:Hoxc5, Hoxc11; Hoxd:Hoxd1, Hoxd12) during the evolutionary process of mammals, which hints the adaptive evolution during mammalian evolutionary process that reflects essential impacts of the modification of Hox-protein function on changes of mammalian axial skeleton and limbs. The vital role of modified Hox-expression parttens and Hox-protein function on mammalian phenotypic changes was evidenced one step future by adaptive mutated sites in main control factors and Hox genes locating in important function domains. Although the positive selection of some genes (Hoxa:Hoxa2, Hoxa7; Hoxb:Hoxb2, Hoxb3, Hoxb4, Hoxc:Hoxc4, Hoxc10; Hoxd:Hoxd1, Hoxd3, Hoxd8; Hoxd9, Hoxd10, Hoxd12; and E2f6, Bmil) in the terminal branch seemly cannot explain the lineage phenotypic modification, they might contribute to the polymorphism of individual axial skeleton and limbs. Also, comparative analysis has showed that phenotypic evolutionary changes might be drived by Hox-expression modification and mutation of Hox coding sequences.We have uncovered evolutionary changes of Hox organization, regulatory factors and Hox coding regions, which play an essential role in the phenotypic adaptive evolution of mammals. Our research enriches the molecular mechanism of mammalian phenotypic changes and provides important molecular basis for mammalian adaptation into diverse habitats.