Logo of embojLink to Publisher's site
EMBO J. 1997 Feb 3; 16(3): 588–598.
PMCID: PMC1169662

Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion.


We have surveyed the tandemly repeated genes encoding U2 snRNA in a diverse panel of humans. We found only two polymorphisms within the U2 repeat unit: a SacI polymorphism (alleles SacI+ or SacI-) and a CT microsatellite polymorphism (alleles CT+ or CT-). Surprisingly, individual U2 tandem arrays are entirely SacI+ or SacI-, and entirely CT+ or CT-, although the SacI and CT alleles can occur in any combination. We also found that polymorphisms in the left and right junction regions flanking the tandem array fall into only two haplotypes (JL+ and JL-, JR+ and JR-). Most surprisingly, JL+ is always associated with JR+, and JL- with JR-. Thus individual U2 arrays do not exchange flanking markers, despite independent assortment and subsequent homogenization of the SacI and CT alleles within the U2 repeat units. We propose that the primary driving force for concerted evolution of the tandem U2 genes is intrachromosomal homogenization; interchromosomal genetic exchanges are much rarer, and reciprocal nonsister chromatid exchange apparently does not occur. Thus concerted evolution of the U2 tandem array occurs in situ along a chromosome lineage, and linkage disequilibrium between sequences flanking the U2 array may persist for long periods of time.

Full Text

The Full Text of this article is available as a PDF (412K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. [PubMed]
  • Dover G. Molecular drive: a cohesive mode of species evolution. Nature. 1982 Sep 9;299(5879):111–117. [PubMed]
  • Dover GA, Linares AR, Bowen T, Hancock JM. Detection and quantification of concerted evolution and molecular drive. Methods Enzymol. 1993;224:525–541. [PubMed]
  • Elder JF, Jr, Turner BJ. Concerted evolution of repetitive DNA sequences in eukaryotes. Q Rev Biol. 1995 Sep;70(3):297–320. [PubMed]
  • Gangloff S, Zou H, Rothstein R. Gene conversion plays the major role in controlling the stability of large tandem repeats in yeast. EMBO J. 1996 Apr 1;15(7):1715–1725. [PMC free article] [PubMed]
  • Gargano S, Wang P, Rusanganwa E, Bacchetti S. The transcriptionally competent U2 gene is necessary and sufficient for adenovirus type 12 induction of the fragile site at 17q21-22. Mol Cell Biol. 1995 Nov;15(11):6256–6261. [PMC free article] [PubMed]
  • Glover TW, Stein CK. Induction of sister chromatid exchanges at common fragile sites. Am J Hum Genet. 1987 Nov;41(5):882–890. [PMC free article] [PubMed]
  • Gonzalez IL, Sylvester JE, Schmickel RD. Human 28S ribosomal RNA sequence heterogeneity. Nucleic Acids Res. 1988 Nov 11;16(21):10213–10224. [PMC free article] [PubMed]
  • Gonzalez IL, Wu S, Li WM, Kuo BA, Sylvester JE. Human ribosomal RNA intergenic spacer sequence. Nucleic Acids Res. 1992 Nov 11;20(21):5846–5846. [PMC free article] [PubMed]
  • Hammarström K, Westin G, Bark C, Zabielski J, Petterson U. Genes and pseudogenes for human U2 RNA. Implications for the mechanism of pseudogene formation. J Mol Biol. 1984 Oct 25;179(2):157–169. [PubMed]
  • Hibner BL, Burke WD, Eickbush TH. Sequence identity in an early chorion multigene family is the result of localized gene conversion. Genetics. 1991 Jul;128(3):595–606. [PMC free article] [PubMed]
  • Hillis DM, Moritz C, Porter CA, Baker RJ. Evidence for biased gene conversion in concerted evolution of ribosomal DNA. Science. 1991 Jan 18;251(4991):308–310. [PubMed]
  • Htun H, Lund E, Westin G, Pettersson U, Dahlberg JE. Nuclease S1-sensitive sites in multigene families: human U2 small nuclear RNA genes. EMBO J. 1985 Jul;4(7):1839–1845. [PMC free article] [PubMed]
  • Jeffreys AJ, Wilson V, Thein SL. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. [PubMed]
  • Jeffreys AJ, Tamaki K, MacLeod A, Monckton DG, Neil DL, Armour JA. Complex gene conversion events in germline mutation at human minisatellites. Nat Genet. 1994 Feb;6(2):136–145. [PubMed]
  • Jinks-Robertson S, Petes TD. Experimental determination of rates of concerted evolution. Methods Enzymol. 1993;224:631–646. [PubMed]
  • Kadyk LC, Hartwell LH. Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics. 1992 Oct;132(2):387–402. [PMC free article] [PubMed]
  • Kadyk LC, Hartwell LH. Replication-dependent sister chromatid recombination in rad1 mutants of Saccharomyces cerevisiae. Genetics. 1993 Mar;133(3):469–487. [PMC free article] [PubMed]
  • Liao D, Weiner AM. Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT)n.(GA)n microsatellite embedded within the U2 repeat unit. Genomics. 1995 Dec 10;30(3):583–593. [PubMed]
  • Lindgren V, Ares M, Jr, Weiner AM, Francke U. Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17. Nature. 1985 Mar 7;314(6006):115–116. [PubMed]
  • Lovett ST, Drapkin PT, Sutera VA, Jr, Gluckman-Peskind TJ. A sister-strand exchange mechanism for recA-independent deletion of repeated DNA sequences in Escherichia coli. Genetics. 1993 Nov;135(3):631–642. [PMC free article] [PubMed]
  • Mangin M, Ares M, Jr, Weiner AM. U1 small nuclear RNA genes are subject to dosage compensation in mouse cells. Science. 1985 Jul 19;229(4710):272–275. [PubMed]
  • Matera AG, Weiner AM, Schmid CW. Structure and evolution of the U2 small nuclear RNA multigene family in primates: gene amplification under natural selection? Mol Cell Biol. 1990 Nov;10(11):5876–5882. [PMC free article] [PubMed]
  • Mellon I, Rajpal DK, Koi M, Boland CR, Champe GN. Transcription-coupled repair deficiency and mutations in human mismatch repair genes. Science. 1996 Apr 26;272(5261):557–560. [PubMed]
  • Charlesworth B, Sniegowski P, Stephan W. The evolutionary dynamics of repetitive DNA in eukaryotes. Nature. 1994 Sep 15;371(6494):215–220. [PubMed]
  • Murti JR, Bumbulis M, Schimenti JC. High-frequency germ line gene conversion in transgenic mice. Mol Cell Biol. 1992 Jun;12(6):2545–2552. [PMC free article] [PubMed]
  • Coen ES, Dover GA. Unequal exchanges and the coevolution of X and Y rDNA arrays in Drosophila melanogaster. Cell. 1983 Jul;33(3):849–855. [PubMed]
  • Murti JR, Bumbulis M, Schimenti JC. Gene conversion between unlinked sequences in the germline of mice. Genetics. 1994 Jul;137(3):837–843. [PMC free article] [PubMed]
  • Nagele R, Freeman T, McMorrow L, Lee HY. Precise spatial positioning of chromosomes during prometaphase: evidence for chromosomal order. Science. 1995 Dec 15;270(5243):1831–1835. [PubMed]
  • Nagylaki T. Evolution of multigene families under interchromosomal gene conversion. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3796–3800. [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]
  • Neuhausen SL, Swensen J, Miki Y, Liu Q, Tavtigian S, Shattuck-Eidens D, Kamb A, Hobbs MR, Gingrich J, Shizuya H, et al. A P1-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1. Hum Mol Genet. 1994 Nov;3(11):1919–1926. [PubMed]
  • Ohta T. Simple model for treating evolution of multigene families. Nature. 1976 Sep 2;263(5572):74–76. [PubMed]
  • Ohta T, Dover GA. Population genetics of multigene families that are dispersed into two or more chromosomes. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4079–4083. [PMC free article] [PubMed]
  • Ozenberger BA, Roeder GS. A unique pathway of double-strand break repair operates in tandemly repeated genes. Mol Cell Biol. 1991 Mar;11(3):1222–1231. [PMC free article] [PubMed]
  • Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993 Dec 17;75(6):1227–1236. [PubMed]
  • Pavelitz T, Rusché L, Matera AG, Scharf JM, Weiner AM. Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. EMBO J. 1995 Jan 3;14(1):169–177. [PMC free article] [PubMed]
  • Petes TD. Molecular genetics of yeast. Annu Rev Biochem. 1980;49:845–876. [PubMed]
  • Rockmill B, Engebrecht JA, Scherthan H, Loidl J, Roeder GS. The yeast MER2 gene is required for chromosome synapsis and the initiation of meiotic recombination. Genetics. 1995 Sep;141(1):49–59. [PMC free article] [PubMed]
  • Schlötterer C, Tautz D. Slippage synthesis of simple sequence DNA. Nucleic Acids Res. 1992 Jan 25;20(2):211–215. [PMC free article] [PubMed]
  • Schlötterer C, Tautz D. Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests intrachromosomal exchanges drive concerted evolution. Curr Biol. 1994 Sep 1;4(9):777–783. [PubMed]
  • Seperack P, Slatkin M, Arnheim N. Linkage disequilibrium in human ribosomal genes: implications for multigene family evolution. Genetics. 1988 Aug;119(4):943–949. [PMC free article] [PubMed]
  • Shiroishi T, Koide T, Yoshino M, Sagai T, Moriwaki K. Hotspots of homologous recombination in mouse meiosis. Adv Biophys. 1995;31:119–132. [PubMed]
  • Shulman MJ, Collins C, Connor A, Read LR, Baker MD. Interchromosomal recombination is suppressed in mammalian somatic cells. EMBO J. 1995 Aug 15;14(16):4102–4107. [PMC free article] [PubMed]
  • Smith GP. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. [PubMed]
  • Sørensen PD, Frederiksen S. Characterization of human 5S rRNA genes. Nucleic Acids Res. 1991 Aug 11;19(15):4147–4151. [PMC free article] [PubMed]
  • Szostak JW, Wu R. Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae. Nature. 1980 Apr 3;284(5755):426–430. [PubMed]
  • Thompson-Stewart D, Karpen GH, Spradling AC. A transposable element can drive the concerted evolution of tandemly repetitious DNA. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9042–9046. [PMC free article] [PubMed]
  • Tishkoff SA, Dietzsch E, Speed W, Pakstis AJ, Kidd JR, Cheung K, Bonné-Tamir B, Santachiara-Benerecetti AS, Moral P, Krings M. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science. 1996 Mar 8;271(5254):1380–1387. [PubMed]
  • Van Arsdell SW, Weiner AM. Human genes for U2 small nuclear RNA are tandemly repeated. Mol Cell Biol. 1984 Mar;4(3):492–499. [PMC free article] [PubMed]
  • Walsh JB. Persistence of tandem arrays: implications for satellite and simple-sequence DNAs. Genetics. 1987 Mar;115(3):553–567. [PMC free article] [PubMed]
  • Warburton PE, Willard HF. Interhomologue sequence variation of alpha satellite DNA from human chromosome 17: evidence for concerted evolution along haplotypic lineages. J Mol Evol. 1995 Dec;41(6):1006–1015. [PubMed]
  • Weiner AM, Denison RA. Either gene amplification or gene conversion may maintain the homogeneity of the multigene family encoding human U1 small nuclear RNA. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):1141–1149. [PubMed]
  • Willard HF. Centromeres of mammalian chromosomes. Trends Genet. 1990 Dec;6(12):410–416. [PubMed]
  • Wolff RK, Plaetke R, Jeffreys AJ, White R. Unequal crossingover between homologous chromosomes is not the major mechanism involved in the generation of new alleles at VNTR loci. Genomics. 1989 Aug;5(2):382–384. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Save items

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence and PMC links.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • 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.
  • OMIM
    Genome Survey Sequence (GSS) nucleotide records reported in the current articles.
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...