Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution (original) (raw)

Abstract

The Alu repetitive family of short interspersed elements (SINEs) in primates can be subdivided into distinct subfamilies by specific diagnostic nucleotide changes. The older subfamilies are generally very abundant, while the younger subfamilies have fewer copies. Some of the youngest Alu elements are absent in the orthologous loci of nonhuman primates, indicative of recent retroposition events, the primary mode of SINE evolution. PCR analysis of one young Alu subfamily (Sb2) member found in the low-density lipoprotein receptor gene apparently revealed the presence of this element in the green monkey, orangutan, gorilla, and chimpanzee genomes, as well as the human genome. However, sequence analysis of these genomes revealed a highly mutated, older, primate-specific Alu element was present at this position in the nonhuman primates. Comparison of the flanking DNA sequences upstream of this Alu insertion corresponded to evolution expected for standard primate phylogeny, but comparison of the Alu repeat sequences revealed that the human element departed from this phylogeny. The change in the human sequence apparently occurred by a gene conversion event only within the Alu element itself, converting it from one of the oldest to one of the youngest Alu subfamilies. Although gene conversions of Alu elements are clearly very rare, this finding shows that such events can occur and contribute to specific cases of SINE subfamily evolution.

Full Text

The Full Text of this article is available as a PDF (306.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batzer M. A., Deininger P. L. A human-specific subfamily of Alu sequences. Genomics. 1991 Mar;9(3):481–487. doi: 10.1016/0888-7543(91)90414-a. [DOI] [PubMed] [Google Scholar]
  2. Batzer M. A., Gudi V. A., Mena J. C., Foltz D. W., Herrera R. J., Deininger P. L. Amplification dynamics of human-specific (HS) Alu family members. Nucleic Acids Res. 1991 Jul 11;19(13):3619–3623. doi: 10.1093/nar/19.13.3619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Batzer M. A., Kilroy G. E., Richard P. E., Shaikh T. H., Desselle T. D., Hoppens C. L., Deininger P. L. Structure and variability of recently inserted Alu family members. Nucleic Acids Res. 1990 Dec 11;18(23):6793–6798. doi: 10.1093/nar/18.23.6793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Batzer M. A., Schmid C. W., Deininger P. L. Evolutionary analyses of repetitive DNA sequences. Methods Enzymol. 1993;224:213–232. doi: 10.1016/0076-6879(93)24017-o. [DOI] [PubMed] [Google Scholar]
  5. Belmaaza A., Wallenburg J. C., Brouillette S., Gusew N., Chartrand P. Genetic exchange between endogenous and exogenous LINE-1 repetitive elements in mouse cells. Nucleic Acids Res. 1990 Nov 11;18(21):6385–6391. doi: 10.1093/nar/18.21.6385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Britten R. J., Baron W. F., Stout D. B., Davidson E. H. Sources and evolution of human Alu repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4770–4774. doi: 10.1073/pnas.85.13.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daniels G. R., Deininger P. L. Integration site preferences of the Alu family and similar repetitive DNA sequences. Nucleic Acids Res. 1985 Dec 20;13(24):8939–8954. doi: 10.1093/nar/13.24.8939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deininger P. L., Batzer M. A., Hutchison C. A., 3rd, Edgell M. H. Master genes in mammalian repetitive DNA amplification. Trends Genet. 1992 Sep;8(9):307–311. doi: 10.1016/0168-9525(92)90262-3. [DOI] [PubMed] [Google Scholar]
  9. Dover G. Molecular drive: a cohesive mode of species evolution. Nature. 1982 Sep 9;299(5879):111–117. doi: 10.1038/299111a0. [DOI] [PubMed] [Google Scholar]
  10. Goldberg Y. P., Rommens J. M., Andrew S. E., Hutchinson G. B., Lin B., Theilmann J., Graham R., Glaves M. L., Starr E., McDonald H. Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease. Nature. 1993 Mar 25;362(6418):370–373. doi: 10.1038/362370a0. [DOI] [PubMed] [Google Scholar]
  11. Horsthemke B., Beisiegel U., Dunning A., Havinga J. R., Williamson R., Humphries S. Unequal crossing-over between two alu-repetitive DNA sequences in the low-density-lipoprotein-receptor gene. A possible mechanism for the defect in a patient with familial hypercholesterolaemia. Eur J Biochem. 1987 Apr 1;164(1):77–81. doi: 10.1111/j.1432-1033.1987.tb10995.x. [DOI] [PubMed] [Google Scholar]
  12. Hutchinson G. B., Andrew S. E., McDonald H., Goldberg Y. P., Graham R., Rommens J. M., Hayden M. R. An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily. Nucleic Acids Res. 1993 Jul 25;21(15):3379–3383. doi: 10.1093/nar/21.15.3379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jurka J. A new subfamily of recently retroposed human Alu repeats. Nucleic Acids Res. 1993 May 11;21(9):2252–2252. doi: 10.1093/nar/21.9.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jurka J., Milosavljevic A. Reconstruction and analysis of human Alu genes. J Mol Evol. 1991 Feb;32(2):105–121. doi: 10.1007/BF02515383. [DOI] [PubMed] [Google Scholar]
  15. Jurka J., Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4775–4778. doi: 10.1073/pnas.85.13.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koop B. F., Goodman M., Xu P., Chan K., Slightom J. L. Primate eta-globin DNA sequences and man's place among the great apes. Nature. 1986 Jan 16;319(6050):234–238. doi: 10.1038/319234a0. [DOI] [PubMed] [Google Scholar]
  17. Leeflang E. P., Chesnokov I. N., Schmid C. W. Mobility of short interspersed repeats within the chimpanzee lineage. J Mol Evol. 1993 Dec;37(6):566–572. doi: 10.1007/BF00182742. [DOI] [PubMed] [Google Scholar]
  18. Leeflang E. P., Liu W. M., Chesnokov I. N., Schmid C. W. Phylogenetic isolation of a human Alu founder gene: drift to new subfamily identity [corrected]. J Mol Evol. 1993 Dec;37(6):559–565. doi: 10.1007/BF00182741. [DOI] [PubMed] [Google Scholar]
  19. Leeflang E. P., Liu W. M., Hashimoto C., Choudary P. V., Schmid C. W. Phylogenetic evidence for multiple Alu source genes. J Mol Evol. 1992 Jul;35(1):7–16. doi: 10.1007/BF00160256. [DOI] [PubMed] [Google Scholar]
  20. Lehrman M. A., Goldstein J. L., Russell D. W., Brown M. S. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987 Mar 13;48(5):827–835. doi: 10.1016/0092-8674(87)90079-1. [DOI] [PubMed] [Google Scholar]
  21. Lehrman M. A., Russell D. W., Goldstein J. L., Brown M. S. Alu-Alu recombination deletes splice acceptor sites and produces secreted low density lipoprotein receptor in a subject with familial hypercholesterolemia. J Biol Chem. 1987 Mar 5;262(7):3354–3361. [PubMed] [Google Scholar]
  22. Martignetti J. A., Brosius J. BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11563–11567. doi: 10.1073/pnas.90.24.11563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McLean J., Wion K., Drayna D., Fielding C., Lawn R. Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression. Nucleic Acids Res. 1986 Dec 9;14(23):9397–9406. doi: 10.1093/nar/14.23.9397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Melamed C., Nevo Y., Kupiec M. Involvement of cDNA in homologous recombination between Ty elements in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Apr;12(4):1613–1620. doi: 10.1128/mcb.12.4.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miyamoto M. M., Koop B. F., Slightom J. L., Goodman M., Tennant M. R. Molecular systematics of higher primates: genealogical relations and classification. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7627–7631. doi: 10.1073/pnas.85.20.7627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Muratani K., Hada T., Yamamoto Y., Kaneko T., Shigeto Y., Ohue T., Furuyama J., Higashino K. Inactivation of the cholinesterase gene by Alu insertion: possible mechanism for human gene transposition. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11315–11319. doi: 10.1073/pnas.88.24.11315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nicholls R. D., Fischel-Ghodsian N., Higgs D. R. Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987 May 8;49(3):369–378. doi: 10.1016/0092-8674(87)90289-3. [DOI] [PubMed] [Google Scholar]
  28. Perna N. T., Batzer M. A., Deininger P. L., Stoneking M. Alu insertion polymorphism: a new type of marker for human population studies. Hum Biol. 1992 Oct;64(5):641–648. [PubMed] [Google Scholar]
  29. Quentin Y. The Alu family developed through successive waves of fixation closely connected with primate lineage history. J Mol Evol. 1988;27(3):194–202. doi: 10.1007/BF02100074. [DOI] [PubMed] [Google Scholar]
  30. Rogers J. H. The origin and evolution of retroposons. Int Rev Cytol. 1985;93:187–279. doi: 10.1016/s0074-7696(08)61375-3. [DOI] [PubMed] [Google Scholar]
  31. Rouyer F., Simmler M. C., Page D. C., Weissenbach J. A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination. Cell. 1987 Nov 6;51(3):417–425. doi: 10.1016/0092-8674(87)90637-4. [DOI] [PubMed] [Google Scholar]
  32. Rüdiger N. S., Heinsvig E. M., Hansen F. A., Faergeman O., Bolund L., Gregersen N. DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia. Clin Genet. 1991 Jun;39(6):451–462. doi: 10.1111/j.1399-0004.1991.tb03057.x. [DOI] [PubMed] [Google Scholar]
  33. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shen M. R., Batzer M. A., Deininger P. L. Evolution of the master Alu gene(s). J Mol Evol. 1991 Oct;33(4):311–320. doi: 10.1007/BF02102862. [DOI] [PubMed] [Google Scholar]
  35. Singer M. F. SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes. Cell. 1982 Mar;28(3):433–434. doi: 10.1016/0092-8674(82)90194-5. [DOI] [PubMed] [Google Scholar]
  36. Slagel V. K., Deininger P. L. In vivo transcription of a cloned prosimian primate SINE sequence. Nucleic Acids Res. 1989 Nov 11;17(21):8669–8682. doi: 10.1093/nar/17.21.8669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Slagel V., Flemington E., Traina-Dorge V., Bradshaw H., Deininger P. Clustering and subfamily relationships of the Alu family in the human genome. Mol Biol Evol. 1987 Jan;4(1):19–29. doi: 10.1093/oxfordjournals.molbev.a040422. [DOI] [PubMed] [Google Scholar]
  38. Stoppa-Lyonnet D., Duponchel C., Meo T., Laurent J., Carter P. E., Arala-Chaves M., Cohen J. H., Dewald G., Goetz J., Hauptmann G. Recombinational biases in the rearranged C1-inhibitor genes of hereditary angioedema patients. Am J Hum Genet. 1991 Nov;49(5):1055–1062. [PMC free article] [PubMed] [Google Scholar]
  39. Vidaud D., Vidaud M., Bahnak B. R., Siguret V., Gispert Sanchez S., Laurian Y., Meyer D., Goossens M., Lavergne J. M. Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene. Eur J Hum Genet. 1993;1(1):30–36. doi: 10.1159/000472385. [DOI] [PubMed] [Google Scholar]
  40. Wallace M. R., Andersen L. B., Saulino A. M., Gregory P. E., Glover T. W., Collins F. S. A de novo Alu insertion results in neurofibromatosis type 1. Nature. 1991 Oct 31;353(6347):864–866. doi: 10.1038/353864a0. [DOI] [PubMed] [Google Scholar]
  41. Willard C., Nguyen H. T., Schmid C. W. Existence of at least three distinct Alu subfamilies. J Mol Evol. 1987;26(3):180–186. doi: 10.1007/BF02099850. [DOI] [PubMed] [Google Scholar]
  42. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]