title: Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes.
abstract: As part of a systematic search for differentially expressed genes, we have isolated a novel transketolase-related gene (TKR) (HGMW-approved symbol TKT), located between the green color vision pigment gene (GCP) and the ABP-280 filamin gene (FLN1) in Xq28. Transcripts encoding tissue-specific protein isoforms could be isolated. Comparison with known transketolases (TK) demonstrated a TKR-specific deletion mutating one thiamine binding site. Genomic sequencing of the TKR gene revealed the presence of a pseudoexon as well as the acquisition of a tissue-specific spliced exon compared to TK. Since it has been postulated that the vertebrate genome arose by two cycles of tetraploidization from a cephalochordate genome, this could represent an example of the modulation of the function of a preexisting transketolase gene by gene duplication. Thiamine defiency is closely involved with two neurological disorders, Beriberi and Wernicke-Korsakoff syndromes, and in both of these conditions TK with altered activity are found. We discuss the possible involvement of TKR in explaining the observed variant transketolase forms.
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Coy
authors.forename: S
authors.initials: S
authors.lastname: Dübel
authors.forename: P
authors.initials: P
authors.lastname: Kioschis
authors.forename: K
authors.initials: K
authors.lastname: Thomas
authors.forename: G
authors.initials: G
authors.lastname: Micklem
authors.forename: H
authors.initials: H
authors.lastname: Delius
authors.forename: A
authors.initials: A
authors.lastname: Poustka
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005318:Fetal Heart / Q000737:chemistry; D005796:Genes / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013831:Thiamine; D014174:Transketolase / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014174:Transketolase; D013831:Thiamine