Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution
<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...
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| Format: | Article |
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BMC
2008-02-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/9/72 |
| _version_ | 1828524180065222656 |
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| author | Malakhova Margarita L Lin Xin Chung Taeowan Zou Xianqiong Pike Helen M Brown Rhoderick E |
| author_facet | Malakhova Margarita L Lin Xin Chung Taeowan Zou Xianqiong Pike Helen M Brown Rhoderick E |
| author_sort | Malakhova Margarita L |
| collection | DOAJ |
| description | <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> |
| first_indexed | 2024-12-11T20:42:38Z |
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| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T20:42:38Z |
| publishDate | 2008-02-01 |
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| spelling | doaj.art-fa80ac22ad504227bcefd04a86dc20572022-12-22T00:51:29ZengBMCBMC Genomics1471-21642008-02-01917210.1186/1471-2164-9-72Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolutionMalakhova Margarita LLin XinChung TaeowanZou XianqiongPike Helen MBrown Rhoderick E<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>http://www.biomedcentral.com/1471-2164/9/72 |
| spellingShingle | Malakhova Margarita L Lin Xin Chung Taeowan Zou Xianqiong Pike Helen M Brown Rhoderick E Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution BMC Genomics |
| title | Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution |
| title_full | Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution |
| title_fullStr | Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution |
| title_full_unstemmed | Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution |
| title_short | Human glycolipid transfer protein (<it>GLTP</it>) genes: organization, transcriptional status and evolution |
| title_sort | human glycolipid transfer protein it gltp it genes organization transcriptional status and evolution |
| url | http://www.biomedcentral.com/1471-2164/9/72 |
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