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Unformatted text preview: dine conversion on replication and, potentially, to large-scale changes in gene expression, as a result of alterations in DNA methylation patterns118. Therefore, the conservation of these dinucleotides in Alu subfamilies might indicate a form of selection for their retention in active Alu elements. This is in contrast with the rest of the Alu sequences, which seem to have evolved at a neutral rate throughout primate evolution35. Alu repeats continue to generate genomic diversity in several ways. Their amplification has resulted in the generation of the largest family of mobile elements in the human genome. Several thousand Alu elements have integrated into the human genome since the divergence of humans and African apes44,46,78,110; some of them have caused new detrimental mutations48. Additionally, recombination between Alu elements has contributed to the generation of human genetic diversity and is responsible for several human genetic disorders48. Many Alu sequences affect gene expression through changes in their own methylation status, whereas the expression of Alu RNA might influence translation levels121,123,124. Alu repeats that have undergone extensive gene conversion influenced the accumulation of SNPs in the genome44,78,110 — a phenomenon that has a significant impact on genetic-linkage studies and on population genetics. Detailed knowledge of the levels of temporal and spatial variation in Alu-related gene conversion will provide further insight into the magnitude of this process. But, most of the newly integrated Alu insertions are an innocuous source of genetic variation with a subset of homoplasy-free Alu-insertion polymorphisms that are useful for studying the relationships between populations, and the evolution and organization of tandemly arrayed gene families44,46,78,110. These elements will also be useful as genomic anchors for comparative genomic studies of the organization of nonhuman primate genomes44,46,78. Future studies of the expansion of recently integrated Alu elements and N ATURE REVIEWS | GENETICS VOLUME 3 | MAY 2002 | 3 7 7 © 2002 Nature Publishing Group REVIEWS
LINEs in non-human primate genomes will allow a detailed analysis of the interplay between the amplification dynamics of these elements, using whole primate genomes as ‘test-tubes’. These types of studies will facilitate an evolutionary examination of the current working hypothesis that Alu elements and LINEs use a common pathway for amplification27. In addition, they will result in the generation of new genetic markers for primate conservation biology and studies of nonhuman primate demographics, as well as providing an insight into the genetic differences between humans and non-human primates. These studies should also shed new light on the biology of these interesting mobile elements and provide a comparative assessment of their role in shaping various non-human primate genomes. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. Deininger, P. L. & Batzer, M. A. Evolution of retroposons. Evol. Biol. 27, 157–196 (1993). Okada, N. SINEs. Curr. Opin. Genet. Dev. 1, 498–504 (1991). 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). Smit, A. F. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr. Opin. Genet. Dev. 9, 657–663 (1999). 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). Schmid, C. W. & Deininger, P. L. Sequence organization of the human genome. Cell 6, 345–358 (1975). Rubin, C. M., Houck, C. M., Deininger, P. L., Friedmann, T. & Schmid, C. W. Partial nucleotide sequence of the 300nucleotide interspersed repeated human DNA sequences. Nature 284, 372–374 (1980). 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). 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. Korenberg, J. R. & Rykowski, M. C. Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands. Cell 53, 391–400 (1988). 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). Deininger, P. L. & Daniels, G. R. The recent evolution of mammalian repetitive DNA elements. Trends Genet. 2, 76–80 (1986). Ullu, E. & Tschudi, C. Alu sequences are processed 7SL RNA genes. Nature 312, 171–172 (1984). Shedlock, A. M. & Okada, N. SINE insertions: powerful tools for molecular systema...
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