Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1993 Oct; 13(10): 6520–6529.
PMCID: PMC364711

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alexandrov IA, Mashkova TD, Akopian TA, Medvedev LI, Kisselev LL, Mitkevich SP, Yurov YB. Chromosome-specific alpha satellites: two distinct families on human chromosome 18. Genomics. 1991 Sep;11(1):15–23. [PubMed]
  • Alexandrov IA, Mitkevich SP, Yurov YB. The phylogeny of human chromosome specific alpha satellites. Chromosoma. 1988;96(6):443–453. [PubMed]
  • Benezra R, Cantor CR, 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. [PubMed]
  • Bernat RL, Delannoy MR, Rothfield NF, Earnshaw WC. Disruption of centromere assembly during interphase inhibits kinetochore morphogenesis and function in mitosis. Cell. 1991 Sep 20;66(6):1229–1238. [PubMed]
  • Brown DD, Wensink PC, 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. [PubMed]
  • Choo KH, 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. [PMC free article] [PubMed]
  • Dover G. Molecular drive: a cohesive mode of species evolution. Nature. 1982 Sep 9;299(5879):111–117. [PubMed]
  • Durfy SJ, Willard HF. 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. [PubMed]
  • Earnshaw WC, Tomkiel JE. Centromere and kinetochore structure. Curr Opin Cell Biol. 1992 Feb;4(1):86–93. [PubMed]
  • Ellison JW, Hood LE. Human antibody genes. Evolutionary and molecular genetic perspectives. Adv Hum Genet. 1983;13:113–147. [PubMed]
  • Ge Y, Wagner MJ, Siciliano M, Wells DE. 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. [PubMed]
  • Haaf T, Warburton PE, Willard HF. 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. [PubMed]
  • Hood L, Campbell JH, Elgin SC. The organization, expression, and evolution of antibody genes and other multigene families. Annu Rev Genet. 1975;9:305–353. [PubMed]
  • Maeda N, Smithies O. The evolution of multigene families: human haptoglobin genes. Annu Rev Genet. 1986;20:81–108. [PubMed]
  • Maio JJ, Brown FL, Musich PR. 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Metzenberg AB, Wurzer G, Huisman TH, Smithies O. Homology requirements for unequal crossing over in humans. Genetics. 1991 May;128(1):143–161. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Musich PR, Brown FL, Maio JJ. 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. [PMC free article] [PubMed]
  • Nagylaki T, Petes TD. Intrachromosomal gene conversion and the maintenance of sequence homogeneity among repeated genes. Genetics. 1982 Feb;100(2):315–337. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Orr-Weaver TL, Szostak JW. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. [PMC free article] [PubMed]
  • Palen TE, Cech TR. Chromatin structure at the replication origins and transcription-initiation regions of the ribosomal RNA genes of Tetrahymena. Cell. 1984 Apr;36(4):933–942. [PubMed]
  • Pluta AF, Saitoh N, Goldberg I, Earnshaw WC. 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Smith GP. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. [PubMed]
  • Southern EM. Long range periodicities in mouse satellite DNA. J Mol Biol. 1975 May 5;94(1):51–69. [PubMed]
  • Strachan T, Webb D, Dover GA. Transition stages of molecular drive in multiple-copy DNA families in Drosophila. EMBO J. 1985 Jul;4(7):1701–1708. [PMC free article] [PubMed]
  • Sumner AT. Scanning electron microscopy of mammalian chromosomes from prophase to telophase. Chromosoma. 1991 Jul;100(6):410–418. [PubMed]
  • 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. [PubMed]
  • Tyler-Smith C, Brown WR. Structure of the major block of alphoid satellite DNA on the human Y chromosome. J Mol Biol. 1987 Jun 5;195(3):457–470. [PubMed]
  • Waldman AS, Liskay RM. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol Cell Biol. 1988 Dec;8(12):5350–5357. [PMC free article] [PubMed]
  • Warburton PE, Greig GM, Haaf T, Willard HF. PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis. Genomics. 1991 Oct;11(2):324–333. [PubMed]
  • Warburton PE, Willard HF. 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. [PubMed]
  • Warburton PE, Willard HF. 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. [PMC free article] [PubMed]
  • Waye JS, Durfy SJ, Pinkel D, Kenwrick S, Patterson M, Davies KE, Willard HF. 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. [PubMed]
  • Waye JS, England SB, Willard HF. 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. [PMC free article] [PubMed]
  • Waye JS, Willard HF. 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. [PMC free article] [PubMed]
  • Waye JS, Willard HF. 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. [PMC free article] [PubMed]
  • Waye JS, Willard HF. 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. [PMC free article] [PubMed]
  • Wevrick R, Willard HF. 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. [PMC free article] [PubMed]
  • Willard HF. Centromeres of mammalian chromosomes. Trends Genet. 1990 Dec;6(12):410–416. [PubMed]
  • Willard HF, Greig GM, Powers VE, Waye JS. Molecular organization and haplotype analysis of centromeric DNA from human chromosome 17: implications for linkage in neurofibromatosis. Genomics. 1987 Dec;1(4):368–373. [PubMed]
  • Willard HF, Smith KD, 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. [PMC free article] [PubMed]
  • Willard HF, Waye JS. 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. [PubMed]
  • Willard HF, Waye JS, Skolnick MH, Schwartz CE, Powers VE, England SB. 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. [PMC free article] [PubMed]
  • Wu KC, 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. [PubMed]
  • Yang TP, Hansen SK, Oishi KK, Ryder OA, Hamkalo BA. 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. [PMC free article] [PubMed]
  • Zhang XY, 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. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Save items

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...