Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution

• Main Authors: Malakhova Margarita L, Lin Xin, Chung Taeowan, Zou Xianqiong, Pike Helen M, Brown Rhoderick E
• Format: Article
• Language: English
• Published: BMC 2008-02-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/9/72

<p>Abstract</p> <p>Background</p> <p>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 <it>GLTP </it>genes.</p> <p>Results</p> <p>In human cells, single-copy <it>GLTP </it>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 (~94%), full-length coding sequence containing all key amino acid residues involved in glycolipid liganding. To establish the transcriptional activity of each human <it>GLTP </it>gene, <it>in silico </it>EST evaluations, RT-PCR amplifications of <it>GLTP </it>transcript(s), and methylation analyses of regulator CpG islands were performed using various human cells. Active transcription was found for 12q24.11 <it>GLTP </it>but 11p15.1 <it>GLTP </it>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 <it>GLTP </it>were highly conserved in therian mammals and other vertebrates. Orthologs of the intronless <it>GLTP </it>gene were observed in primates but not in rodentiates, carnivorates, cetartiodactylates, or didelphimorphiates, consistent with recent evolutionary development.</p> <p>Conclusion</p> <p>The results identify and characterize the gene responsible for GLTP expression in humans and provide the first evidence for the existence of a <it>GLTP </it>pseudogene, while demonstrating the rigorous approach needed to unequivocally distinguish transcriptionally-active retrogenes from silent pseudogenes. The results also rectify errors in the <it>Ensembl </it>database regarding the organizational structure of the actively transcribed <it>GLTP </it>gene in <it>Pan troglodytes </it>and establish the intronless <it>GLTP </it>as a primate-specific, processed pseudogene marker. A solid foundation has been established for future identification of hereditary defects in human <it>GLTP </it>genes.</p>