title: Gene duplications and losses among vertebrate deoxyribonucleoside kinases of the non-TK1 Family.
abstract: Deoxyribonucleoside kinases (dNKs) salvage deoxyribonucleosides (dNs) and catalyze the rate limiting step of this salvage pathway by converting dNs into corresponding monophosphate forms. These enzymes serve as an excellent model to study duplicated genes and their evolutionary history. So far, among vertebrates only four mammalian dNKs have been studied for their substrate specificity and kinetic properties. However, some vertebrates, such as fish, frogs, and birds, apparently possess a duplicated homolog of deoxycytidine kinase (dCK). In this study, we characterized a family of dCK/deoxyguanosine kinase (dGK)-like enzymes from a frog Xenopus laevis and a bird Gallus gallus. We showed that X. laevis has a duplicated dCK gene and a dGK gene, whereas G. gallus has a duplicated dCK gene but has lost the dGK gene. We cloned, expressed, purified, and subsequently determined the kinetic parameters of the dCK/dGK enzymes encoded by these genes. The two dCK enzymes in G. gallus have broader substrate specificity than their human or X. laevis counterparts. Additionally, the duplicated dCK enzyme in G. gallus might have become mitochondria. Based on our study we postulate that changing and adapting substrate specificities and subcellular localization are likely the drivers behind the evolution of vertebrate dNKs.
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Mutahir
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.|e Lund Protein Production Platform, Lund University , Lund , Sweden.
authors.forename: Louise Slot
authors.initials: LS
authors.lastname: Christiansen
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.
authors.forename: Anders R
authors.initials: AR
authors.lastname: Clausen
authors.affiliation: b Department of Biology , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Berchtold
authors.affiliation: c ZGene A/S Hørsholm , Denmark.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gojkovic
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.|d Department of Science , Systems and Models, Roskilde University , Roskilde , Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Munch-Petersen
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.|e Lund Protein Production Platform, Lund University , Lund , Sweden.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knecht
authors.affiliation: a Department of Biology , Lund University , Lund , Sweden.
authors.forename: Jure
authors.initials: J
authors.lastname: Piškur
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics*; D002645:Chickens; D019143:Evolution, Molecular; D017353:Gene Deletion; D020440:Gene Duplication; D007700:Kinetics; D009928:Organ Specificity; D013937:Thymidine Kinase / Q000737:chemistry / Q000235:genetics*; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D030161:Avian Proteins; D029867:Xenopus Proteins; C105339:thymidine kinase 2; D013937:Thymidine Kinase
keywords: Gallus gallus; Nucleoside salvage pathway; Xenopus laevis; deoxyribonucleosides; evolution