title: Molecular Evolution of the TET Gene Family in Mammals.
abstract: Ten-eleven translocation (TET) proteins, a family of Fe(2+)- and 2-oxoglutarate-dependent dioxygenases, are involved in DNA demethylation. They also help regulate various cellular functions. Three TET paralogs have been identified (TET1, TET2, and TET3) in humans. This study focuses on the evolution of mammalian TET genes. Distinct patterns in TET1 and TET2 vs. TET3 were revealed by codon-based tests of positive selection. Results indicate that TET1 and TET2 genes have experienced positive selection more frequently than TET3 gene, and that the majority of codon sites evolved under strong negative selection. These findings imply that the selective pressure on TET3 may have been relaxed in several lineages during the course of evolution. Our analysis of convergent amino acid substitutions also supports the different evolutionary dynamics among TET gene subfamily members. All of the five amino acid sites that are inferred to have evolved under positive selection in the catalytic domain of TET2 are localized at the protein's outer surface. The adaptive changes of these positively selected amino acid sites could be associated with dynamic interactions between other TET-interacting proteins, and positive selection thus appears to shift the regulatory scheme of TET enzyme function.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. h.akahori@gmail.com.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akahori
authors.affiliation: Department of Statistics, the University of Auckland, Auckland 1010, New Zealand. s.guindon@auckland.ac.nz.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Guindon
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. s3502004@edu.gifu-u.ac.jp.
authors.forename: Sumio
authors.initials: S
authors.lastname: Yoshizaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. ymuto@gifu-u.ac.jp.|Department of Functional Bioscience, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1193, Japan. ymuto@gifu-u.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Muto
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D003062:Codon; D049308:Dioxygenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D008322:Mammals / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D005810:Multigene Family; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012641:Selection, Genetic
chemical_list: D003062:Codon; D049308:Dioxygenases
keywords: mammal; molecular evolution; positive selection; ten-eleven translocation (TET) protein