Generation of a pseudogene during retroviral infection
Tóm tắt
During evolution, up to 10% of the mammalian genome may have arisen by rare retroposition events. This process involves reverse transcription of RNA intermediates that originate from retroviral and retrovial-like sequences, highly and middle repetitive DNA elements, and processed pseudogenes. The mechanism, and contemporary nature, for retrotransposition of the viral family and long interspersed elements has been well studied; however, it has proven difficult to demonstrate that the process by which pseudogenes retropose is continuing. In this report a mutation in the murine hypoxanthine-guanosine phosphoribosyl transferase (hprt) gene, which was previously isolated following retroviral infection of ES cells, is shown to result from a de novo retroposition of an α-tubulin pseudogene. Repair of this insertion by homologous recombination restores the activity of the hprt locus, thus confirming the site of mutation. This retroposon bears all the hallmarks of a naturally processed pseudogene [intron loss, presence of a poly(A) tail, and target site duplication] while the retroposition event took place at a known time in well-defined conditions, during retroviral infection of ES cells. The study of this mutation demonstrates that under appropriate conditions pseudogenes of protein-coding genes can still retropose in the mammalian genome. The coincidence of this mutagenic event with retroviral infection suggests that in this situation the reverse transcriptase may have had a retroviral origin, which would implicate a retroviral role in facilitating pseudogene formation.
Tài liệu tham khảo
Deininger, P.L. (1989). SINEs: short interspersed repeated DNA elements in higher eukaryotes. In Mobile DNA, D. Berg, M. Howe, eds. (Washington, DC: American Society for Microbiology), pp. 619–636.
Deragon, J.M., Sinnett, D., Labuda, D. (1990). Reverse transcriptase activity from human embryonal carcinoma cells NTera2D1. EMBO J. 9, 3363–3368.
Dornburg, R., Temin, H.M. (1990). cDNA genes formed after infection with retroviral vector particles lack the hallmarks of natural processed pseudogenes. Mol. Cell. Biol. 10, 68–74.
Elliott, E.M., Henderson, G., Sarangi, F., Ling, V. (1986). Complete sequence of three alpha-tubulin cDNAs in Chinese hamster ovary cells: each encodes a distinct alpha-tubulin isoprotein. Mol. Cell. Biol. 6, 906–913.
Friedrich, G., Soriano, P. (1991). Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5, 1513–1523.
Heidmann, O., Heidmann, T. (1991). Retrotransposition of a mouse IAP sequence tagged with an indicator gene. Cell 64, 886–889.
Hutchison III, C.A., Hardies, S.C., Loeb, D.D., Shehee, W.R., Edgell, M.H. (1989). LINEs and related retroposons: long interspersed repeated sequences in the eukaryotic genome. In Mobile DNA, D. Berg, M. Howe, eds. (Washington, DC: American Siciety for Microbiology), pp. 593–617.
Kazazian, H.H., Wong, C., Youssoufian, M., Scott, A.F., Phillips, D.G., Antonarakis, S.E. (1988). Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature 332, 164–166.
Kuehn, M.R., Bradley, A., Robertson, E.J., Evans, M.J. (1987). A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326, 295–298.
Levine, K.L., Syteiner, B., Johnson, K., Aronoff, R., Quinton, T.J., Linial, M.L. (1990). Unusual features of integrated cDNAs generated by infection with genome-free retroviruses. Mol. Cell. Biol. 10, 1891–1900.
Lewis, S.A., Cowan, N.J. (1986). Tubulin pseudogenes as markers for hominoid divergence. J. Mol. Biol. 187, 623–626.
Lewis, S.A., Lee, M.G., Cowan, N.J. (1985). Five mouse tubulin isotypes and their regulated expression during development. J. Cell. Biol. 101, 852–861.
Linial, M. (1987). Creation of a processed pseudogene by retroviral infection. Cell 49, 93–102.
Martin, S.L. (1991). Ribonucleoprotein particles with LINE-1 RNA in mouse embryonal carcinoma cells. Mol. Cell. Biol. 11, 4804–4807.
Mathias, S.L., Scott, A.F., Kazazian, H.H., Boek, J.D., Gabriel, A. (1991). Reverse transcriptase encoded by a human transposable element. Science 254, 1808–1810.
Melton, D., Konecki, D., Brennand, J., Caskey, C. (1984). Structure, expression and mutation of the hypoxanthine phosphoribosyl transferase gene. Proc. Natl. Acad. Sci. USA 81, 2147–2151.
Morse, B., Rotherg, P.G., South, V.J., Spandorfer, J.M., Astrin, S.M. (1988). Insertional mutagensis of the myc locus by a LINE-1 sequence in a human breast carcinoma. Nature 333, 87–90.
Mullenbach, R. (1989). An efficient salt-chloroform extraction of DNA from blood and tissues. Trends Genet. 5, 391.
Navone, N.A., Bianchi, A.B., Angel, J.A., Conti, C.C. (1992). A novel polymorphism near the mouse Int-2 locus. Mamm. Genome 3, 296–297.
Rogers, J. (1985). The origin and evolution of retroposons. Int. Rev. Cytol. 93, 187–279.
Sakai, Y., Hattori, M., Fujita, A., Yoshioka, K., Kuhara, S., Takenaka, O. (1986). The LINE-1 family of primates may encode a reverse transcriptase-like protein. Cold Spring Harbor Symp. Quant. Biol. 51, 465–469.
Sambrook, J., Fritsch, E.F., Maniatis, T. (1989). Molecular cloning: A Laboratory Manual, 2nd ed. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press).
Stocking, C., Kolleck, R., Bergholz, U., Ostertag, W. (1985). Long terminal repeat sequences impart haematopoietic transformation properties to the myeloproliferative sarcoma virus. Proc. Natl. Acad. Sci. USA 82, 5746–5750.
Tchenio, T., Segal-Bendirdjian, E., Heidmann, T. (1993). Generation of processed pseudogenes in murine cells. EMBO J. 12, 1487–1497.
Thomas, K.R., Cappechi, M.R. (1987). Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503–512.
Varmus, H.E., Brown P.O., (1989). Retroviruses. In Mobile DNA, D. Berg, M. Howe, eds. (Washington, DC: American Society for Microbiology), pp. 53–108.
Villasante, A., Wang, D., Dobner, P., Dolph, P., Lewis, S.A., Cowan, N.J. (1986). Six mouse α-Tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes. Mol. Cell. Biol. 6, 2409–2419.
Wallace, M.R., Andersen, L.B., Saulino, A.M., Gregory, P.E., Glover, T.W., Collins, F.S., (1991). A de novo Alu insertion results in neurofibromatosis type 1. Nature 353, 864–866.
Weiner, A., Deininger, P.L., Efstratiadis, A. (1986). Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem. 55, 631–661.