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Transduction of the Human gene FAM8A1 by endogenous retrovirus during priamte evolution

Genomics 2001 Nov;78(1-2):38-45. Transduction of the Human gene FAM8A1 by endogenous retrovirus during priamte evolution Jamain S, Girondot M, Leroy P, Clergue M, Quach H, Fellous M, Bourgeron T. Laboratoire d 'Immunogenetique Humaine, INSERM E021,

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Transduction of the Human gene FAM8A1 by endogenous retrovirus during priamte evolution

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  1. Genomics 2001 Nov;78(1-2):38-45 • Transduction of the Human gene FAM8A1 • by endogenous retrovirus during priamte evolution • Jamain S, Girondot M, Leroy P, Clergue M, Quach H, Fellous M, Bourgeron T.Laboratoire d 'Immunogenetique Humaine, INSERM E021, • Institut Pasteur, 25, rue du Docteur Roux, Paris Cedex 15, 75724, France. Joo-Mi Yi 2002. 3. 11. Molecular Biology and Pylogeny Lab.

  2. Introduction 1. This retrotransposition process can be achieved by different mechanisms involving retroviruses or other repetitive elements present in the genome and through capture of cellular mRNAs by retroviruses, a process termed transduction 2. Orphan human gene, FAM8A1(family with sequence similarity 8; originally called AHCP for autosomal highly conserved protein), was captured by a retrovirus during primate evolution through resembles oncogene transduction 3. This gene, localized on chromosome 6p23, produced multiple, closely related, processed pseudogenes(FAM8A2P-A6P) each inserted in HERV-K sequences. 4. The presence of different FAM8A1 psudogenes suggests that this retroelement (ERV+FAM8A1 pseudogenes) has been copied and inserted in different places in the genome by retrotransposition 5. This sis the first record of cellular mRNA transduction in humans, but other genes mat be captured by this process during the HERV cycle, presenting a potential cause of mutation and disease.

  3. Results - Isolating the FAM8A1 gene - Evolutionary conservation of the FAM8A1 gene

  4. - Expression of the FAM8A1 gene

  5. 2 6p21 6q23 11 Y 6p23 • - Characterization of human FAM8A1 pseudogenes • Phylogenetic relationship among the FAM8A1 pseudogene sequences • - Date of FAM8A1 pseudogene spread

  6. nonfunctional functional -Substitution pattern and evidence for gene conservation in FAM8A1 pseudogene sequences

  7. Reference figure HERVK14 AHCP

  8. 1. FAM8A1 mRNA and HERVK14 undergo illegitimate recombination during reverse transcription. 2. First strand switch –S2 3. Second strand switch–S1 4. Complete FAM8A1 transduction 5. Ancestral retroposon (ERV+ FAM8A1 psudogene) is inserted in the genome Model for FAM8A1 transduction showing postulated events in the creation of FAM8A1 psuedogenes

  9. References 1.Lower, R. (1999) The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends Microbiol. 7:350-356 2. Schwartz, J. R., Duesburg, S., and Duesburg, P. H. (1995). DNA recombination is sufficient for retroviral replication. Science 259:234-238 3.Medstrand, P., and Blomberg, J. (1993) Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues. J. Virol. 67:6778-6787

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