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Alu repeats and human genomic diversity

Key Points

  • Alu elements are a class of short interspersed elements (SINEs) that have expanded to a copy number of more than one million elements in primate genomes.

  • The expansion of Alu elements is characterized by the dispersal, in a series of subfamilies, of elements of different evolutionary age that share common nucleotide substitutions.

  • Alu elements have an impact on the genome in several ways, including insertion mutations, recombination between elements, gene conversion and gene expression.

  • The human diseases caused by Alu insertions include neurofibromatosis, haemophilia, familial hypercholesterolaemia, breast cancer, insulin-resistant diabetes type II and Ewing sarcoma.

  • Alu elements alter the distribution of methylation and, possibly, transcription of genes throughout the genome.

  • The transcription of Alu elements changes in response to cellular stress and might be involved in maintaining or regulating the cellular stress response.

  • Alu elements are a primary source for the origin of simple sequence repeats in primate genomes.

  • Alu-insertion polymorphisms are a boon for the study of human population genetics and primate comparative genomics because they are neutral, identical-by-descent genetic markers with known ancestral states.


During the past 65 million years, Alu elements have propagated to more than one million copies in primate genomes, which has resulted in the generation of a series of Alu subfamilies of different ages. Alu elements affect the genome in several ways, causing insertion mutations, recombination between elements, gene conversion and alterations in gene expression. Alu-insertion polymorphisms are a boon for the study of human population genetics and primate comparative genomics because they are neutral genetic markers of identical descent with known ancestral states.

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Figure 1: Alignment of Alu-subfamily consensus sequences.
Figure 2: The expansion of Alu elements in primates.
Figure 3: Expansion of recently integrated human Alu subfamilies.
Figure 4: Spread of an Alu insertion.
Figure 5: Schematic of Alu-induced damage to the human genome.


  1. 1

    Deininger, P. L. & Batzer, M. A. Evolution of retroposons. Evol. Biol. 27, 157–196 (1993).

    Google Scholar 

  2. 2

    Okada, N. SINEs. Curr. Opin. Genet. Dev. 1, 498–504 (1991).

    CAS  PubMed  Google Scholar 

  3. 3

    Schmid, C. W. Alu: structure, origin, evolution, significance and function of one-tenth of human DNA. Prog. Nucleic Acids Res. Mol. Biol. 53, 283–319 (1996).

    CAS  Google Scholar 

  4. 4

    Smit, A. F. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr. Opin. Genet. Dev. 9, 657–663 (1999).

    CAS  Google Scholar 

  5. 5

    Houck, C. M., Rinehart, F. P. & Schmid, C. W. A ubiquitous family of repeated DNA sequences in the human genome. J. Mol. Biol. 132, 289–306 (1979).

    CAS  PubMed  Google Scholar 

  6. 6

    Schmid, C. W. & Deininger, P. L. Sequence organization of the human genome. Cell 6, 345–358 (1975).

    CAS  PubMed  Google Scholar 

  7. 7

    Rubin, C. M., Houck, C. M., Deininger, P. L., Friedmann, T. & Schmid, C. W. Partial nucleotide sequence of the 300-nucleotide interspersed repeated human DNA sequences. Nature 284, 372–374 (1980).

    CAS  PubMed  Google Scholar 

  8. 8

    Deininger, P. L., Jolly, D. J., Rubin, C. M., Friedmann, T. & Schmid, C. W. Base sequence studies of 300 nucleotide renatured repeated human DNA clones. J. Mol. Biol. 151, 17–33 (1981).

    CAS  PubMed  Google Scholar 

  9. 9

    International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).An assembly and annotation of the first draft sequence of the entire human genome that includes a comprehensive analysis of repeated DNA sequences.

  10. 10

    Korenberg, J. R. & Rykowski, M. C. Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands. Cell 53, 391–400 (1988).

    CAS  PubMed  Google Scholar 

  11. 11

    Chen, C., Gentles, A. J., Jurka, J. & Karlin, S. Genes, pseudogenes, and Alu sequence organization across human chromosomes 21 and 22. Proc. Natl Acad. Sci. USA 99, 2930–2935 (2002).

    CAS  PubMed  Google Scholar 

  12. 12

    Deininger, P. L. & Daniels, G. R. The recent evolution of mammalian repetitive DNA elements. Trends Genet. 2, 76–80 (1986).

    CAS  Google Scholar 

  13. 13

    Ullu, E. & Tschudi, C. Alu sequences are processed 7SL RNA genes. Nature 312, 171–172 (1984).

    CAS  PubMed  Google Scholar 

  14. 14

    Shedlock, A. M. & Okada, N. SINE insertions: powerful tools for molecular systematics. Bioessays 22, 148–160 (2000).

    CAS  PubMed  Google Scholar 

  15. 15

    Ohshima, K., Hamada, M., Terai, Y. & Okada, N. The 3′ ends of tRNA-derived short interspersed repetitive elements are derived from the 3′ ends of long interspersed repetitive elements. Mol. Cell. Biol. 16, 3756–3764 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Ohshima, K. & Okada, N. Generality of the tRNA origin of short interspersed repetitive elements (SINEs). Characterization of three different tRNA-derived retroposons in the octopus. J. Mol. Biol. 243, 25–37 (1994).

    CAS  PubMed  Google Scholar 

  17. 17

    Okada, N. & Hamada, M. The 3′ ends of tRNA-derived SINEs originated from the 3′ ends of LINEs: a new example from the bovine genome. J. Mol. Evol. 44, S52–S56 (1997).

    CAS  PubMed  Google Scholar 

  18. 18

    Okada, N. & Ohshima, K. A model for the mechanism of initial generation of short interspersed elements (SINEs). J. Mol. Evol. 37, 167–170 (1993).

    CAS  PubMed  Google Scholar 

  19. 19

    Rogers, J. Retroposons defined. Nature 301, 460 (1983).

    CAS  PubMed  Google Scholar 

  20. 20

    Feng, Q., Moran, J. V., Kazazian, H. H. Jr & Boeke, J. D. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87, 905–916 (1996).

    CAS  Google Scholar 

  21. 21

    Moran, J. V. et al. High frequency retrotransposition in cultured mammalian cells. Cell 87, 917–927 (1996).This manuscript presents the development and characterization of an in vitro assay to measure retrotransposition in mammalian cells.

    CAS  Google Scholar 

  22. 22

    Luan, D. D., Korman, M. H., Jakubczak, J. L. & Eickbush, T. H. Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72, 595–605 (1993).The authors provide strong experimental evidence for the role of target-primed reverse transcription in retroelement mobilization.

    CAS  Google Scholar 

  23. 23

    Shen, M. R., Brosius, J. & Deininger, P. L. BC1 RNA, the transcript from a master gene for ID element amplification, is able to prime its own reverse transcription. Nucleic Acids Res. 25, 1641–1648 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Mathias, S. L., Scott, A. F., Kazazian, H. H. Jr, Boeke, J. D. & Gabriel, A. Reverse transcriptase encoded by a human transposable element. Science 254, 1808–1810 (1991).

    CAS  Google Scholar 

  25. 25

    Deragon, J. M., Sinnett, D. & Labuda, D. Reverse transcriptase activity from human embryonal carcinoma cells NTera2D1. EMBO J. 9, 3363–3368 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Jurka, J. Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons. Proc. Natl Acad. Sci. USA 94, 1872–1877 (1997).This paper provides the first computational evidence for the involvement of enzymatic activity in the integration of retroposons in the genome.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Boeke, J. D. LINEs and Alus — the polyA connection. Nature Genet. 16, 6–7 (1997).

    CAS  Google Scholar 

  28. 28

    Fanning, T. G. & Singer, M. F. LINE-1: a mammalian transposable element. Biochim. Biophys. Acta 910, 203–212 (1987).

    CAS  PubMed  Google Scholar 

  29. 29

    Skowronski, J. & Singer, M. F. The abundant LINE-1 family of repeated DNA sequences in mammals: genes and pseudogenes. Cold Spring Harb. Symp. Quant. Biol. 51, 457–464 (1986).

    CAS  PubMed  Google Scholar 

  30. 30

    Deininger, P. L., Batzer, M. A., Hutchison, C. A. & Edgell, M. H. Master genes in mammalian repetitive DNA amplification. Trends Genet. 8, 307–311 (1992).A comparison of amplification models for mobile elements that are proposed as a result of the initial discovery of mobile-element subfamily structure.

    CAS  PubMed  Google Scholar 

  31. 31

    Paulson, K. E. & Schmid, C. W. Transcriptional inactivity of Alu repeats in HeLa cells. Nucleic Acids Res. 14, 6145–6158 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Ullu, E. & Weiner, A. M. Upstream sequences modulate the internal promoter of the human 7SL RNA gene. Nature 318, 371–374 (1985).

    CAS  PubMed  Google Scholar 

  33. 33

    Batzer, M. A. et al. Standardized nomenclature for Alu repeats. J. Mol. Evol. 42, 3–6 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Labuda, D. & Striker, G. Sequence conservation in Alu evolution. Nucleic Acids Res. 17, 2477–2491 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Batzer, M. A. et al. Structure and variability of recently inserted Alu family members. Nucleic Acids Res. 18, 6793–6798 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Arcot, S. S., Wang, Z., Weber, J. L., Deininger, P. L. & Batzer, M. A. Alu repeats: a source for the genesis of primate microsatellites. Genomics 29, 136–144 (1995).

    CAS  PubMed  Google Scholar 

  37. 37

    Economou, E. P., Bergen, A. W., Warren, A. C. & Antonarakis, S. E. The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome. Proc. Natl Acad. Sci. USA 87, 2951–2954 (1990).

    CAS  PubMed  Google Scholar 

  38. 38

    Jurka, J. & Pethiyagoda, C. Simple repetitive DNA sequences from primates: compilation and analysis. J. Mol. Evol. 40, 120–126 (1995).

    CAS  PubMed  Google Scholar 

  39. 39

    Zuliani, G. & Hobbs, H. H. A high frequency of length polymorphisms in repeated sequences adjacent to Alu sequences. Am. J. Hum. Genet. 46, 963–969 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Toth, G., Gaspari, Z. & Jurka, J. Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res. 10, 967–981 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Beckman, J. S. & Weber, J. L. Survey of human and rat microsatellites. Genomics 12, 627–631 (1992).

    CAS  PubMed  Google Scholar 

  42. 42

    Aleman, C., Roy-Engel, A. M., Shaikh, T. H. & Deininger, P. L. Cis-acting influences on Alu RNA levels. Nucleic Acids Res. 28, 4755–4761 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Shaikh, T. H., Roy, A. M., Kim, J., Batzer, M. A. & Deininger, P. L. cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts. J. Mol. Biol. 271, 222–234 (1997).

    CAS  PubMed  Google Scholar 

  44. 44

    Carroll, M. L. et al. Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to human genomic diversity. J. Mol. Biol. 311, 17–40 (2001).

    CAS  PubMed  Google Scholar 

  45. 45

    Roy, A. M. et al. Recently integrated human Alu repeats: finding needles in the haystack. Genetica 107, 149–161 (1999).

    CAS  PubMed  Google Scholar 

  46. 46

    Roy-Engel, A. M. et al. Alu insertion polymorphisms for the study of human genomic diversity. Genetics 159, 279–290 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Shen, M. R., Batzer, M. A. & Deininger, P. L. Evolution of the master Alu gene(s). J. Mol. Evol. 33, 311–320 (1991).

    CAS  PubMed  Google Scholar 

  48. 48

    Deininger, P. L. & Batzer, M. A. Alu repeats and human disease. Mol. Genet. Metab. 67, 183–193 (1999).This article provides an overview of the data that show a role for Alu elements in human genetic instability and disease.

    CAS  PubMed  Google Scholar 

  49. 49

    Misra, S. & Rio, D. C. Cytotype control of Drosophila P element transposition: the 66 kd protein is a repressor of transposase activity. Cell 62, 269–284 (1990).

    CAS  PubMed  Google Scholar 

  50. 50

    Deininger, P. L. & Slagel, V. K. Recently amplified Alu family members share a common parental Alu sequence. Mol. Cell. Biol. 8, 4566–4569 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Batzer, M. A. & Deininger, P. L. A human-specific subfamily of Alu sequences. Genomics 9, 481–487 (1991).

    CAS  PubMed  Google Scholar 

  52. 52

    Matera, A. G., Hellmann, U. & Schmid, C. W. A transpositionally and transcriptionally competent Alu subfamily. Mol. Cell. Biol. 10, 5424–5432 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Batzer, M. A. et al. Amplification dynamics of human-specific (HS) Alu family members. Nucleic Acids Res. 19, 3619–3623 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Batzer, M. A. et al. Dispersion and insertion polymorphism in two small subfamilies of recently amplified human Alu repeats. J. Mol. Biol. 247, 418–427 (1995).

    CAS  PubMed  Google Scholar 

  55. 55

    Jurka, J. A new subfamily of recently retroposed human Alu repeats. Nucleic Acids Res. 21, 2252 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Leeflang, E. P., Chesnokov, I. N. & Schmid, C. W. Mobility of short interspersed repeats within the chimpanzee lineage. J. Mol. Evol. 37, 566–572 (1993).

    CAS  PubMed  Google Scholar 

  57. 57

    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. J. Mol. Evol. 37, 559–565 (1993).

    CAS  PubMed  Google Scholar 

  58. 58

    Leeflang, E. P., Liu, W. M., Hashimoto, C., Choudary, P. V. & Schmid, C. W. Phylogenetic evidence for multiple Alu source genes. J. Mol. Evol. 35, 7–16 (1992).

    CAS  PubMed  Google Scholar 

  59. 59

    Batzer, M. A. et al. African origin of human-specific polymorphic Alu insertions. Proc. Natl Acad. Sci. USA 91, 12288–12292 (1994).This paper shows the use of Alu elements for the study of human population genetics and includes the first comprehensive survey of Alu-insertion-polymorphism-related human variation.

    CAS  PubMed  Google Scholar 

  60. 60

    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. 64, 641–648 (1992).

    CAS  PubMed  Google Scholar 

  61. 61

    Arcot, S. S. et al. Alu fossil relics — distribution and insertion polymorphism. Genome Res. 6, 1084–1092 (1996).

    CAS  PubMed  Google Scholar 

  62. 62

    Bamshad, M. et al. Genetic evidence on the origins of Indian caste populations. Genome Res. 11, 994–1004 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Batzer, M. A. et al. Genetic variation of recent Alu insertions in human populations. J. Mol. Evol. 42, 22–29 (1996).

    CAS  PubMed  Google Scholar 

  64. 64

    Comas, D. et al. Alu insertion polymorphisms in NW Africa and the Iberian Peninsula: evidence for a strong genetic boundary through the Gibraltar Straits. Hum. Genet. 107, 312–319 (2000).

    CAS  PubMed  Google Scholar 

  65. 65

    Jorde, L. B. et al. The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. Am. J. Hum. Genet. 66, 979–988 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Nasidze, I. et al. Alu insertion polymorphisms and the genetic structure of human populations from the Caucasus. Eur. J. Hum. Genet. 9, 267–272 (2001).

    CAS  PubMed  Google Scholar 

  67. 67

    Novick, G. E. et al. Polymorphic Alu insertions and the Asian origin of Native American populations. Hum. Biol. 70, 23–39 (1998).

    CAS  PubMed  Google Scholar 

  68. 68

    Sherry, S. T., Harpending, H. C., Batzer, M. A. & Stoneking, M. Alu evolution in human populations: using the coalescent to estimate effective population size. Genetics 147, 1977–1982 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Stoneking, M. et al. Alu insertion polymorphisms and human evolution: evidence for a larger population size in Africa. Genome Res. 7, 1061–1071 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Watkins, W. S. et al. Patterns of ancestral human diversity: an analysis of Alu-insertion and restriction-site polymorphisms. Am. J. Hum. Genet. 68, 738–752 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Hammer, M. F. A recent insertion of an Alu element on the Y chromosome is a useful marker for human population studies. Mol. Biol. Evol. 11, 749–761 (1994).

    CAS  PubMed  Google Scholar 

  72. 72

    Shimamura, M. et al. Molecular evidence from retroposons that whales form a clade within even-toed ungulates. Nature 388, 666–670 (1997).In this manuscript, the authors use SINE insertions to study the phylogenetic origin of whales.

    CAS  Google Scholar 

  73. 73

    Nikaido, M., Rooney, A. P. & Okada, N. Phylogenetic relationships among cetartiodactyls based on insertions of short and long interspersed elements: hippopotamuses are the closest extant relatives of whales. Proc. Natl Acad. Sci. USA 96, 10261–10266 (1999).

    CAS  Google Scholar 

  74. 74

    Nikaido, M. et al. Evolution of CHR-2 SINEs in cetartiodactyl genomes: possible evidence for the monophyletic origin of toothed whales. Mamm. Genome 12, 909–915 (2001).

    CAS  PubMed  Google Scholar 

  75. 75

    Nikaido, M. et al. Retroposon analysis of major cetacean lineages: the monophyly of toothed whales and the paraphyly of river dolphins. Proc. Natl Acad. Sci. USA 98, 7384–7389 (2001).

    CAS  PubMed  Google Scholar 

  76. 76

    Hillis, D. M. SINEs of the perfect character. Proc. Natl Acad. Sci. USA 96, 9979–9981 (1999).

    CAS  Google Scholar 

  77. 77

    Cantrell, M. A. et al. An ancient retrovirus-like element contains hot spots for SINE insertion. Genetics 158, 769–777 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Roy-Engel, A. M. et al. Non-traditional Alu evolution and primate genomic diversity. J. Mol. Biol. 316, 1033–1040 (2002).

    CAS  Google Scholar 

  79. 79

    Edwards, M. C. & Gibbs, R. A. A human dimorphism resulting from loss of an Alu. Genomics 14, 590–597 (1992).

    CAS  PubMed  Google Scholar 

  80. 80

    Nakamura, Y. et al. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science 235, 1616–1622 (1987).

    CAS  PubMed  Google Scholar 

  81. 81

    Botstein, D., White, R. L., Skolnick, M. & Davis, R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32, 314–331 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Brookes, A. J. The essence of SNPs. Gene 234, 177–186 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Chakravarti, A. It's raining SNPs, hallelujah? Nature Genet. 19, 216–217 (1998).

    CAS  PubMed  Google Scholar 

  84. 84

    Pennisi, E. A closer look at SNPs suggests difficulties. Science 281, 1787–1789 (1998).

    CAS  PubMed  Google Scholar 

  85. 85

    Britten, R. J. DNA sequence insertion and evolutionary variation in gene regulation. Proc. Natl Acad. Sci. USA 93, 9374–9377 (1996).

    CAS  PubMed  Google Scholar 

  86. 86

    Britten, R. J. Mobile elements inserted in the distant past have taken on important functions. Gene 205, 177–182 (1997).A thorough compilation of mobile elements, which have been functionally significant in the genome.

    CAS  Google Scholar 

  87. 87

    Makalowski, W., Mitchell, G. A. & Labuda, D. Alu sequences in the coding regions of mRNA: a source of protein variability. Trends Genet. 10, 188–193 (1994).

    CAS  PubMed  Google Scholar 

  88. 88

    Norris, J. et al. Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J. Biol. Chem. 270, 22777–22782 (1995).

    CAS  PubMed  Google Scholar 

  89. 89

    Szabo, Z. et al. Sequential loss of two neighboring exons of the tropoelastin gene during primate evolution. J. Mol. Evol. 49, 664–671 (1999).

    CAS  PubMed  Google Scholar 

  90. 90

    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. 4, 19–29 (1987).One of the first reports of subfamily structure in Alu elements.

    CAS  PubMed  Google Scholar 

  91. 91

    Waldman, A. S. & Liskay, R. M. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol. Cell. Biol. 8, 5350–5357 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Lobachev, K. S. et al. Inverted Alu repeats unstable in yeast are excluded from the human genome. EMBO J. 19, 3822–3830 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Stenger, J. E. et al. Biased distribution of inverted and direct Alus in the human genome: implications for insertion, exclusion, and genome stability. Genome Res. 11, 12–27 (2001).

    CAS  PubMed  Google Scholar 

  94. 94

    Gebow, D., Miselis, N. & Liber, H. L. Homologous and nonhomologous recombination resulting in deletion: effects of p53 status, microhomology, and repetitive DNA length and orientation. Mol. Cell. Biol. 20, 4028–4035 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Hsu, S. J., Erickson, R. P., Zhang, J., Garver, W. S. & Heidenreich, R. A. Fine linkage and physical mapping suggests cross-over suppression with a retroposon insertion at the npc1 mutation. Mamm. Genome 11, 774–778 (2000).

    CAS  PubMed  Google Scholar 

  96. 96

    Rieder, M. J., Taylor, S. L., Clark, A. G. & Nickerson, D. A. Sequence variation in the human angiotensin converting enzyme. Nature Genet. 22, 59–62 (1999).

    CAS  PubMed  Google Scholar 

  97. 97

    Arcot, S. S. et al. High-resolution cartography of recently integrated human chromosome 19-specific Alu fossils. J. Mol. Biol. 281, 843–856 (1998).

    CAS  PubMed  Google Scholar 

  98. 98

    Brookfield, J. F. Selection on Alu sequences? Curr. Biol. 11, 900–901 (2001).

    Google Scholar 

  99. 99

    Iizuka, M., Jones, C., Hayashi, K. & Sekiya, T. Mapping of 28 (CA)n microsatellite repeats and 13 Alu markers on human chromosome 11 using a panel of somatic cell hybrids. Genomics 19, 581–584 (1994).

    CAS  PubMed  Google Scholar 

  100. 100

    Schlotterer, C. & Tautz, D. Slippage synthesis of simple sequence DNA. Nucleic Acids Res. 20, 211–215 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101

    Levinson, G. & Gutman, G. A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol. Biol. Evol. 4, 203–221 (1987).

    CAS  Google Scholar 

  102. 102

    Justice, C. M. et al. Phylogenetic analysis of the Friedreich ataxia GAA trinucleotide repeat. J. Mol. Evol. 52, 232–238 (2001).

    CAS  PubMed  Google Scholar 

  103. 103

    Campuzano, V. et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271, 1423–1427 (1996).

    CAS  Google Scholar 

  104. 104

    Knight, A. et al. DNA sequences of Alu elements indicate a recent replacement of the human autosomal genetic complement. Proc. Natl Acad. Sci. USA 93, 4360–4364 (1996).

    CAS  PubMed  Google Scholar 

  105. 105

    Ryan, S. C., Zielinski, R. & Dugaiczyk, A. Structure of the gorilla α-fetoprotein gene and the divergence of primates. Genomics 9, 60–72 (1991).

    CAS  PubMed  Google Scholar 

  106. 106

    Nishio, H., Hamdi, H. K. & Dugaiczyk, A. Genomic expansion across the albumin gene family on human chromosome 4q is directional. Biol. Chem. 380, 1431–1434 (1999).

    CAS  PubMed  Google Scholar 

  107. 107

    Bailey, W. J. et al. Molecular evolution of the ψɛ-globin gene locus: gibbon phylogeny and the hominoid slowdown. Mol. Biol. Evol. 8, 155–184 (1991).

    CAS  PubMed  Google Scholar 

  108. 108

    Koop, B. F. et al. Tarsius δ- and β-globin genes: conversions, evolution, and systematic implications. J. Biol. Chem. 264, 68–79 (1989).

    CAS  PubMed  Google Scholar 

  109. 109

    Kass, D. H., Batzer, M. A. & Deininger, P. L. Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution. Mol. Cell. Biol. 15, 19–25 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110

    Roy, A. M. et al. Potential gene conversion and source genes for recently integrated Alu elements. Genome Res. 10, 1485–1495 (2000).In this paper, the authors provide an initial estimate of the impact of gene conversion on the sequence diversity of Alu elements.

    CAS  PubMed  Google Scholar 

  111. 111

    Maeda, N., Wu, C. I., Bliska, J. & Reneke, J. Molecular evolution of intergenic DNA in higher primates: pattern of DNA changes, molecular clock, and evolution of repetitive sequences. Mol. Biol. Evol. 5, 1–20 (1988).

    CAS  Google Scholar 

  112. 112

    Hayakawa, T., Satta, Y., Gagneux, P., Varki, A. & Takahata, N. Alu-mediated inactivation of the human CMP-N-acetylneuraminic acid hydroxylase gene. Proc. Natl Acad. Sci. USA 98, 11399–11404 (2001).

    CAS  PubMed  Google Scholar 

  113. 113

    Hoff, E. F., Levin, H. L. & Boeke, J. D. Schizosaccharomyces pombe retrotransposon Tf2 mobilizes primarily through homologous cDNA recombination. Mol. Cell. Biol. 18, 6839–6852 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Ardlie, K. et al. Lower-than-expected linkage disequilibrium between tightly linked markers in humans suggests a role for gene conversion. Am. J. Hum. Genet. 69, 582–589 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Frisse, L. et al. Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am. J. Hum. Genet. 69, 831–843 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116

    Rubin, C. M., VandeVoort, C. A., Teplitz, R. L. & Schmid, C. W. Alu repeated DNAs are differentially methylated in primate germ cells. Nucleic Acids Res. 22, 5121–5127 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117

    Schmid, C. W. Human Alu subfamilies and their methylation revealed by blot hybridization. Nucleic Acids Res. 19, 5613–5617 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118

    Bird, A. P. DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 8, 1499–1504 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Liu, W. M., Maraia, R. J., Rubin, C. M. & Schmid, C. W. Alu transcripts: cytoplasmic localisation and regulation by DNA methylation. Nucleic Acids Res. 22, 1087–1095 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Liu, W. M. & Schmid, C. W. Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation. Nucleic Acids Res. 21, 1351–1359 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121

    Li, T. & Schmid, C. W. Differential stress induction of individual Alu loci: implications for transcription and retrotransposition. Gene 276, 135–141 (2001).

    CAS  PubMed  Google Scholar 

  122. 122

    Liu, W. M., Chu, W. M., Choudary, P. V. & Schmid, C. W. Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Res. 23, 1758–1765 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Schmid, C. W. Does SINE evolution preclude Alu function? Nucleic Acids Res. 26, 4541–4550 (1998).An interesting discussion of the evidence for potential functional roles for Alu sequences.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124

    Li, T., Spearow, J., Rubin, C. M. & Schmid, C. W. Physiological stresses increase mouse short interspersed element (SINE) RNA expression in vivo. Gene 239, 367–372 (1999).

    CAS  PubMed  Google Scholar 

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Research on mobile elements in the Batzer and Deininger labs is supported by the National Institutes of Health, Department of the Army, Louisiana Board of Regents Millennium Trust Health Excellence Fund and the Office of Justice Programs, National Institute of Justice, Department of Justice. The points of view in this document are those of the authors and do not necessarily represent the official position of the US Department of Justice.

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Correspondence to Mark A. Batzer.

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CMP-N-acetylneuraminic acid hydroxylase





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Batzer laboratory

Deininger laboratory

Dolan DNA Learning Center, Cold Spring Harbor Laboratory — Genetic Origins and Alu Insertion Polymorphism

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A class of repetitive DNA that is made up of repeats that are 2–8 nucleotides in length. They can be highly polymorphic and are frequently used as molecular markers in population genetics studies.


A class of repetitive sequences, 7–100 nucleotides each, that span 500–20,000 bp, and are especially located throughout the genome, towards chromosome ends.


A DNA sequence that was derived originally from a functional protein-coding gene that has lost its function owing to the presence of one or more inactivating mutations.


A plot of DNA annealing as a function of DNA concentration and time. The amount of DNA (as a percentage) that has renatured (reassociated/reannealed) plotted against 'C0t', where 'C0' refers to the initial DNA concentration and 't' is the time of renaturation.


The number of nucleotide differences between two aligned DNA sequences.


Loci in two species that are derived from a common ancestral locus by a speciation event. This is different from paralogous members of a gene family that are derived from duplication events.


Random changes in allele frequency that result from the sampling of gametes from generation to generation.


Similarity due to independent evolutionary change; an allelic variant (such as a nucleotide variant or a mobile-element insertion at a particular location) that is present in two or more genes, but absent in their common ancestor.


The soluble precursor of elastin (one of the most hydrophobic proteins known). Mammalian tropoelastin is a moderately conserved protein.


(LOH). A loss of one of the alleles at a given locus as a result of a genomic change, such as mitotic deletion, gene conversion or chromosome missegregration.


A non-reciprocal recombination process that results in an alteration of the sequence of a gene to that of its homologue during meiosis.

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Batzer, M., Deininger, P. Alu repeats and human genomic diversity. Nat Rev Genet 3, 370–379 (2002).

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