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. 1993 Oct;13(10):6520–6529. doi: 10.1128/mcb.13.10.6520

Nonrandom localization of recombination events in human alpha satellite repeat unit variants: implications for higher-order structural characteristics within centromeric heterochromatin.

P E Warburton 1, J S Waye 1, H F Willard 1
PMCID: PMC364711  PMID: 8413251

Abstract

Tandemly repeated DNA families appear to undergo concerted evolution, such that repeat units within a species have a higher degree of sequence similarity than repeat units from even closely related species. While intraspecies homogenization of repeat units can be explained satisfactorily by repeated rounds of genetic exchange processes such as unequal crossing over and/or gene conversion, the parameters controlling these processes remain largely unknown. Alpha satellite DNA is a noncoding tandemly repeated DNA family found at the centromeres of all human and primate chromosomes. We have used sequence analysis to investigate the molecular basis of 13 variant alpha satellite repeat units, allowing comparison of multiple independent recombination events in closely related DNA sequences. The distribution of these events within the 171-bp monomer is nonrandom and clusters in a distinct 20- to 25-bp region, suggesting possible effects of primary sequence and/or chromatin structure. The position of these recombination events may be associated with the location within the higher-order repeat unit of the binding site for the centromere-specific protein CENP-B. These studies have implications for the molecular nature of genetic recombination, mechanisms of concerted evolution, and higher-order structure of centromeric heterochromatin.

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Selected References

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

  1. Alexandrov I. A., Mashkova T. D., Akopian T. A., Medvedev L. I., Kisselev L. L., Mitkevich S. P., Yurov Y. B. Chromosome-specific alpha satellites: two distinct families on human chromosome 18. Genomics. 1991 Sep;11(1):15–23. doi: 10.1016/0888-7543(91)90097-x. [DOI] [PubMed] [Google Scholar]
  2. Alexandrov I. A., Mitkevich S. P., Yurov Y. B. The phylogeny of human chromosome specific alpha satellites. Chromosoma. 1988;96(6):443–453. doi: 10.1007/BF00303039. [DOI] [PubMed] [Google Scholar]
  3. Benezra R., Cantor C. R., Axel R. Nucleosomes are phased along the mouse beta-major globin gene in erythroid and nonerythroid cells. Cell. 1986 Mar 14;44(5):697–704. doi: 10.1016/0092-8674(86)90835-4. [DOI] [PubMed] [Google Scholar]
  4. Bernat R. L., Delannoy M. R., Rothfield N. F., Earnshaw W. C. Disruption of centromere assembly during interphase inhibits kinetochore morphogenesis and function in mitosis. Cell. 1991 Sep 20;66(6):1229–1238. doi: 10.1016/0092-8674(91)90045-z. [DOI] [PubMed] [Google Scholar]
  5. Brown D. D., Wensink P. C., Jordan E. A comparison of the ribosomal DNA's of Xenopus laevis and Xenopus mulleri: the evolution of tandem genes. J Mol Biol. 1972 Jan 14;63(1):57–73. doi: 10.1016/0022-2836(72)90521-9. [DOI] [PubMed] [Google Scholar]
  6. Choo K. H., Vissel B., Nagy A., Earle E., Kalitsis P. A survey of the genomic distribution of alpha satellite DNA on all the human chromosomes, and derivation of a new consensus sequence. Nucleic Acids Res. 1991 Mar 25;19(6):1179–1182. doi: 10.1093/nar/19.6.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Durfy S. J., Willard H. F. Patterns of intra- and interarray sequence variation in alpha satellite from the human X chromosome: evidence for short-range homogenization of tandemly repeated DNA sequences. Genomics. 1989 Nov;5(4):810–821. doi: 10.1016/0888-7543(89)90123-7. [DOI] [PubMed] [Google Scholar]
  9. Earnshaw W. C., Tomkiel J. E. Centromere and kinetochore structure. Curr Opin Cell Biol. 1992 Feb;4(1):86–93. doi: 10.1016/0955-0674(92)90063-i. [DOI] [PubMed] [Google Scholar]
  10. Ellison J. W., Hood L. E. Human antibody genes. Evolutionary and molecular genetic perspectives. Adv Hum Genet. 1983;13:113–147. [PubMed] [Google Scholar]
  11. Ge Y., Wagner M. J., Siciliano M., Wells D. E. Sequence, higher order repeat structure, and long-range organization of alpha satellite DNA specific to human chromosome 8. Genomics. 1992 Jul;13(3):585–593. doi: 10.1016/0888-7543(92)90128-f. [DOI] [PubMed] [Google Scholar]
  12. Haaf T., Warburton P. E., Willard H. F. Integration of human alpha-satellite DNA into simian chromosomes: centromere protein binding and disruption of normal chromosome segregation. Cell. 1992 Aug 21;70(4):681–696. doi: 10.1016/0092-8674(92)90436-g. [DOI] [PubMed] [Google Scholar]
  13. Hood L., Campbell J. H., Elgin S. C. The organization, expression, and evolution of antibody genes and other multigene families. Annu Rev Genet. 1975;9:305–353. doi: 10.1146/annurev.ge.09.120175.001513. [DOI] [PubMed] [Google Scholar]
  14. Maeda N., Smithies O. The evolution of multigene families: human haptoglobin genes. Annu Rev Genet. 1986;20:81–108. doi: 10.1146/annurev.ge.20.120186.000501. [DOI] [PubMed] [Google Scholar]
  15. Maio J. J., Brown F. L., Musich P. R. Subunit structure of chromatin and the organization of eukaryotic highly repetitive DNA: recurrent periodicities and models for the evolutionary origins of repetitive DNA. J Mol Biol. 1977 Dec 15;117(3):637–655. doi: 10.1016/0022-2836(77)90062-6. [DOI] [PubMed] [Google Scholar]
  16. Masumoto H., Masukata H., Muro Y., Nozaki N., Okazaki T. A human centromere antigen (CENP-B) interacts with a short specific sequence in alphoid DNA, a human centromeric satellite. J Cell Biol. 1989 Nov;109(5):1963–1973. doi: 10.1083/jcb.109.5.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Metzenberg A. B., Wurzer G., Huisman T. H., Smithies O. Homology requirements for unequal crossing over in humans. Genetics. 1991 May;128(1):143–161. doi: 10.1093/genetics/128.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muro Y., Masumoto H., Yoda K., Nozaki N., Ohashi M., Okazaki T. Centromere protein B assembles human centromeric alpha-satellite DNA at the 17-bp sequence, CENP-B box. J Cell Biol. 1992 Feb;116(3):585–596. doi: 10.1083/jcb.116.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Musich P. R., Brown F. L., Maio J. J. Nucleosome phasing and micrococcal nuclease cleavage of African green monkey component alpha DNA. Proc Natl Acad Sci U S A. 1982 Jan;79(1):118–122. doi: 10.1073/pnas.79.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nagylaki T., Petes T. D. Intrachromosomal gene conversion and the maintenance of sequence homogeneity among repeated genes. Genetics. 1982 Feb;100(2):315–337. doi: 10.1093/genetics/100.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Okumura K., Kiyama R., Oishi M. Sequence analyses of extrachromosomal Sau3A and related family DNA: analysis of recombination in the excision event. Nucleic Acids Res. 1987 Sep 25;15(18):7477–7489. doi: 10.1093/nar/15.18.7477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Orr-Weaver T. L., Szostak J. W. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. doi: 10.1128/mr.49.1.33-58.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Palen T. E., Cech T. R. Chromatin structure at the replication origins and transcription-initiation regions of the ribosomal RNA genes of Tetrahymena. Cell. 1984 Apr;36(4):933–942. doi: 10.1016/0092-8674(84)90043-6. [DOI] [PubMed] [Google Scholar]
  24. Pluta A. F., Saitoh N., Goldberg I., Earnshaw W. C. Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere. J Cell Biol. 1992 Mar;116(5):1081–1093. doi: 10.1083/jcb.116.5.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rubnitz J., Subramani S. The minimum amount of homology required for homologous recombination in mammalian cells. Mol Cell Biol. 1984 Nov;4(11):2253–2258. doi: 10.1128/mcb.4.11.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith G. P. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. doi: 10.1126/science.1251186. [DOI] [PubMed] [Google Scholar]
  27. Southern E. M. Long range periodicities in mouse satellite DNA. J Mol Biol. 1975 May 5;94(1):51–69. doi: 10.1016/0022-2836(75)90404-0. [DOI] [PubMed] [Google Scholar]
  28. Strachan T., Webb D., Dover G. A. Transition stages of molecular drive in multiple-copy DNA families in Drosophila. EMBO J. 1985 Jul;4(7):1701–1708. doi: 10.1002/j.1460-2075.1985.tb03839.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sumner A. T. Scanning electron microscopy of mammalian chromosomes from prophase to telophase. Chromosoma. 1991 Jul;100(6):410–418. doi: 10.1007/BF00337519. [DOI] [PubMed] [Google Scholar]
  30. Tudor M., Lobocka M., Goodell M., Pettitt J., O'Hare K. The pogo transposable element family of Drosophila melanogaster. Mol Gen Genet. 1992 Mar;232(1):126–134. doi: 10.1007/BF00299145. [DOI] [PubMed] [Google Scholar]
  31. Tyler-Smith C., Brown W. R. Structure of the major block of alphoid satellite DNA on the human Y chromosome. J Mol Biol. 1987 Jun 5;195(3):457–470. doi: 10.1016/0022-2836(87)90175-6. [DOI] [PubMed] [Google Scholar]
  32. Waldman A. S., Liskay R. M. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol Cell Biol. 1988 Dec;8(12):5350–5357. doi: 10.1128/mcb.8.12.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Warburton P. E., Greig G. M., Haaf T., Willard H. F. PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis. Genomics. 1991 Oct;11(2):324–333. doi: 10.1016/0888-7543(91)90139-6. [DOI] [PubMed] [Google Scholar]
  34. Warburton P. E., Willard H. F. Genomic analysis of sequence variation in tandemly repeated DNA. Evidence for localized homogeneous sequence domains within arrays of alpha-satellite DNA. J Mol Biol. 1990 Nov 5;216(1):3–16. doi: 10.1016/s0022-2836(05)80056-7. [DOI] [PubMed] [Google Scholar]
  35. Warburton P. E., Willard H. F. PCR amplification of tandemly repeated DNA: analysis of intra- and interchromosomal sequence variation and homologous unequal crossing-over in human alpha satellite DNA. Nucleic Acids Res. 1992 Nov 25;20(22):6033–6042. doi: 10.1093/nar/20.22.6033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Waye J. S., Durfy S. J., Pinkel D., Kenwrick S., Patterson M., Davies K. E., Willard H. F. Chromosome-specific alpha satellite DNA from human chromosome 1: hierarchical structure and genomic organization of a polymorphic domain spanning several hundred kilobase pairs of centromeric DNA. Genomics. 1987 Sep;1(1):43–51. doi: 10.1016/0888-7543(87)90103-0. [DOI] [PubMed] [Google Scholar]
  37. Waye J. S., England S. B., Willard H. F. Genomic organization of alpha satellite DNA on human chromosome 7: evidence for two distinct alphoid domains on a single chromosome. Mol Cell Biol. 1987 Jan;7(1):349–356. doi: 10.1128/mcb.7.1.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Waye J. S., Willard H. F. Chromosome-specific alpha satellite DNA: nucleotide sequence analysis of the 2.0 kilobasepair repeat from the human X chromosome. Nucleic Acids Res. 1985 Apr 25;13(8):2731–2743. doi: 10.1093/nar/13.8.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Waye J. S., Willard H. F. Molecular analysis of a deletion polymorphism in alpha satellite of human chromosome 17: evidence for homologous unequal crossing-over and subsequent fixation. Nucleic Acids Res. 1986 Sep 11;14(17):6915–6927. doi: 10.1093/nar/14.17.6915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Waye J. S., Willard H. F. Structure, organization, and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal crossing-over and an ancestral pentamer repeat shared with the human X chromosome. Mol Cell Biol. 1986 Sep;6(9):3156–3165. doi: 10.1128/mcb.6.9.3156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wevrick R., Willard H. F. Long-range organization of tandem arrays of alpha satellite DNA at the centromeres of human chromosomes: high-frequency array-length polymorphism and meiotic stability. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9394–9398. doi: 10.1073/pnas.86.23.9394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Willard H. F. Centromeres of mammalian chromosomes. Trends Genet. 1990 Dec;6(12):410–416. doi: 10.1016/0168-9525(90)90302-m. [DOI] [PubMed] [Google Scholar]
  43. Willard H. F., Greig G. M., Powers V. E., Waye J. S. Molecular organization and haplotype analysis of centromeric DNA from human chromosome 17: implications for linkage in neurofibromatosis. Genomics. 1987 Dec;1(4):368–373. doi: 10.1016/0888-7543(87)90041-3. [DOI] [PubMed] [Google Scholar]
  44. Willard H. F., Smith K. D., Sutherland J. Isolation and characterization of a major tandem repeat family from the human X chromosome. Nucleic Acids Res. 1983 Apr 11;11(7):2017–2033. doi: 10.1093/nar/11.7.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Willard H. F., Waye J. S. Chromosome-specific subsets of human alpha satellite DNA: analysis of sequence divergence within and between chromosomal subsets and evidence for an ancestral pentameric repeat. J Mol Evol. 1987;25(3):207–214. doi: 10.1007/BF02100014. [DOI] [PubMed] [Google Scholar]
  46. Willard H. F., Waye J. S., Skolnick M. H., Schwartz C. E., Powers V. E., England S. B. Detection of restriction fragment length polymorphisms at the centromeres of human chromosomes by using chromosome-specific alpha satellite DNA probes: implications for development of centromere-based genetic linkage maps. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5611–5615. doi: 10.1073/pnas.83.15.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wu K. C., Strauss F., Varshavsky A. Nucleosome arrangement in green monkey alpha-satellite chromatin. Superimposition of non-random and apparently random patterns. J Mol Biol. 1983 Oct 15;170(1):93–117. doi: 10.1016/s0022-2836(83)80228-9. [DOI] [PubMed] [Google Scholar]
  48. Yang T. P., Hansen S. K., Oishi K. K., Ryder O. A., Hamkalo B. A. Characterization of a cloned repetitive DNA sequence concentrated on the human X chromosome. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6593–6597. doi: 10.1073/pnas.79.21.6593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zhang X. Y., Fittler F., Hörz W. Eight different highly specific nucleosome phases on alpha-satellite DNA in the African green monkey. Nucleic Acids Res. 1983 Jul 11;11(13):4287–4306. doi: 10.1093/nar/11.13.4287. [DOI] [PMC free article] [PubMed] [Google Scholar]

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