title: Natural selection and functional diversification of the epidermal growth factor receptor EGFR family in vertebrates.
abstract: BACKGROUND
  Genes that have been subject to adaptive evolution can produce varying degrees of pathology or differing symptomatology. ErbB family receptor activation will initiate a number of downstream signaling pathways, such as mitogen-activated protein kinase (MAPK), activator of transcription (STAT), the modulation of calcium channels, and so on, all of which lead to aggressive tumor behavior. However, the evolutionary mechanisms operating in the retention of ErbB family genes and the changes in selection pressures are not clear.
  
  
  RESULTS
  Sixty-two full-length cDNA sequences from 27 vertebrate species were extracted from the UniProt protein database, NCBI's GenBank and the Ensembl database. The result of phylogenetic analysis showed that the four ErbB family members in vertebrates might be formed by gene duplication. In order to determine the mode of evolution in vertebrates, selection analysis and functional divergence analysis were combined to explain the relationship of the site-specific evolution and functional divergence in the vertebrate ErbB family. Our results indicate that the acceleration of asymmetric evolutionary rates and purifying selection together were the main force for the production of ErbBs, and positive selections were detected in the ErbB family.
  
  
  CONCLUSIONS
  An evolutional phylogeny of 27 vertebrates was presented in our study; the tree showed that the genes have evolved through duplications followed by purifying selection, except for seven sites, which evolved by positive selection. There was one common site with positive selection and functional divergence. In the process of functional differentiation evolving through gene duplication, relaxed selection may play an important part.
authors.affiliation: School of Pharmacy, Guangdong Medical College, Dongguan, Guangdong, PR China. liuyong0614@126.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenwu
authors.initials: W
authors.lastname: He
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Long
authors.forename: Feng
authors.initials: F
authors.lastname: Pang
authors.forename: Lei
authors.initials: L
authors.lastname: Xian
authors.forename: Mingwu
authors.initials: M
authors.lastname: Chen
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D020440:Gene Duplication; D018773:Genes, erbB-1; D008969:Molecular Sequence Data; D010802:Phylogeny; D012641:Selection, Genetic; D014714:Vertebrates / Q000235:genetics
chemical_list: D066246:ErbB Receptors