MOLECULAR-CLONING OF TISSUE-SPECIFIC TRANSCRIPTS OF A TRANSKETOLASE-RELATED GENE - IMPLICATIONS FOR THE EVOLUTION OF NEW VERTEBRATE GENES

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 tis sue-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 th e presence of a pseudoexon as well as the acquisition of a tissue-spec ific spliced exon compared to TR. Since it has been postulated that th e vertebrate genome arose by two cycles of tetraploidization from a ce phalochordate genome, this could represent an example of the modulatio n of the function of a preexisting transketolase gene by gene duplicat ion, Thiamine defiency is closely involved with two neurological disor ders, 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 f orms. (C) 1996 Academic Press, Inc.