title: Human glycolipid transfer protein (GLTP) genes: organization, transcriptional status and evolution.
abstract: BACKGROUND
  Glycolipid transfer protein is the prototypical and founding member of the new GLTP superfamily distinguished by a novel conformational fold and glycolipid binding motif. The present investigation provides the first insights into the organization, transcriptional status, phylogenetic/evolutionary relationships of GLTP genes.
  
  
  RESULTS
  In human cells, single-copy GLTP genes were found in chromosomes 11 and 12. The gene at locus 11p15.1 exhibited several features of a potentially active retrogene, including a highly homologous (approximately 94%), full-length coding sequence containing all key amino acid residues involved in glycolipid liganding. To establish the transcriptional activity of each human GLTP gene, in silico EST evaluations, RT-PCR amplifications of GLTP transcript(s), and methylation analyses of regulator CpG islands were performed using various human cells. Active transcription was found for 12q24.11 GLTP but 11p15.1 GLTP was transcriptionally silent. Heterologous expression and purification of the GLTP paralogs showed glycolipid intermembrane transfer activity only for 12q24.11 GLTP. Phylogenetic/evolutionary analyses indicated that the 5-exon/4-intron organizational pattern and encoded sequence of 12q24.11 GLTP were highly conserved in therian mammals and other vertebrates. Orthologs of the intronless GLTP gene were observed in primates but not in rodentiates, carnivorates, cetartiodactylates, or didelphimorphiates, consistent with recent evolutionary development.
  
  
  CONCLUSIONS
  The results identify and characterize the gene responsible for GLTP expression in humans and provide the first evidence for the existence of a GLTP pseudogene, while demonstrating the rigorous approach needed to unequivocally distinguish transcriptionally-active retrogenes from silent pseudogenes. The results also rectify errors in the Ensembl database regarding the organizational structure of the actively transcribed GLTP gene in Pan troglodytes and establish the intronless GLTP as a primate-specific, processed pseudogene marker. A solid foundation has been established for future identification of hereditary defects in human GLTP genes.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA. xzou@hi.umn.edu
authors.forename: Xianqiong
authors.initials: X
authors.lastname: Zou
authors.forename: Taeowan
authors.initials: T
authors.lastname: Chung
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Malakhova
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pike
authors.forename: Rhoderick E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C511922:GLTP protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins