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EMBO J. 1995 Jan 3; 14(1): 169–177.
PMCID: PMC398064

Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus.


In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous within each species but differs somewhat between species. Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages. The data suggest that the U2 tandem repeat, once established in the primate lineage, contained sequence elements favoring perpetuation and concerted evolution of the array in situ, despite a pericentric inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon and other Old World monkeys with the 6 kb U2 repeat unit in humans and other hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a 5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of the provirus by homologous recombination between the LTRs generated a 6 kb U2 repeat unit containing a solo LTR. Remarkably, both junctions between the human U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR sequence, suggesting a role for the LTR in the origin or maintenance of the primate U2 array.

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  • Amstutz H, Munz P, Heyer WD, Leupoid U, Kohli J. Concerted evolution of tRNA genes: intergenic conversion among three unlinked serine tRNA genes in S. pombe. Cell. 1985 Apr;40(4):879–886. [PubMed]
  • Ares M, Jr, Chung JS, Giglio L, Weiner AM. Distinct factors with Sp1 and NF-A specificities bind to adjacent functional elements of the human U2 snRNA gene enhancer. Genes Dev. 1987 Oct;1(8):808–817. [PubMed]
  • Armour JA, Jeffreys AJ. Biology and applications of human minisatellite loci. Curr Opin Genet Dev. 1992 Dec;2(6):850–856. [PubMed]
  • Armour JA, Wong Z, Wilson V, Royle NJ, Jeffreys AJ. Sequences flanking the repeat arrays of human minisatellites: association with tandem and dispersed repeat elements. Nucleic Acids Res. 1989 Jul 11;17(13):4925–4935. [PMC free article] [PubMed]
  • Armour JA, Harris PC, Jeffreys AJ. Allelic diversity at minisatellite MS205 (D16S309): evidence for polarized variability. Hum Mol Genet. 1993 Aug;2(8):1137–1145. [PubMed]
  • Bernstein LB, Manser T, Weiner AM. Human U1 small nuclear RNA genes: extensive conservation of flanking sequences suggests cycles of gene amplification and transposition. Mol Cell Biol. 1985 Sep;5(9):2159–2171. [PMC free article] [PubMed]
  • Bollag RJ, Elwood DR, Tobin ED, Godwin AR, Liskay RM. Formation of heteroduplex DNA during mammalian intrachromosomal gene conversion. Mol Cell Biol. 1992 Apr;12(4):1546–1552. [PMC free article] [PubMed]
  • Buetti E. Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity. Mol Cell Biol. 1994 Feb;14(2):1191–1203. [PMC free article] [PubMed]
  • Caporossi D, Bacchetti S, Nicoletti B. Synergism between aphidicolin and adenoviruses in the induction of breaks at fragile sites on human chromosomes. Cancer Genet Cytogenet. 1991 Jul 1;54(1):39–53. [PubMed]
  • Collins C, Kuo WL, Segraves R, Fuscoe J, Pinkel D, Gray JW. Construction and characterization of plasmid libraries enriched in sequences from single human chromosomes. Genomics. 1991 Dec;11(4):997–1006. [PubMed]
  • Curtis D, Clark SH, Chovnick A, Bender W. Molecular analysis of recombination events in Drosophila. Genetics. 1989 Jul;122(3):653–661. [PMC free article] [PubMed]
  • Djian P, Green H. Vectorial expansion of the involucrin gene and the relatedness of the hominoids. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8447–8451. [PMC free article] [PubMed]
  • Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH., Jr Isolation of an active human transposable element. Science. 1991 Dec 20;254(5039):1805–1808. [PubMed]
  • Doolittle RF, Feng DF. Tracing the origin of retroviruses. Curr Top Microbiol Immunol. 1992;176:195–211. [PubMed]
  • Dover GA. Evolution of genetic redundancy for advanced players. Curr Opin Genet Dev. 1993 Dec;3(6):902–910. [PubMed]
  • Durnam DM, Menninger JC, Chandler SH, Smith PP, McDougall JK. A fragile site in the human U2 small nuclear RNA gene cluster is revealed by adenovirus type 12 infection. Mol Cell Biol. 1988 May;8(5):1863–1867. [PMC free article] [PubMed]
  • Eikenboom JC, Vink T, Briët E, Sixma JJ, Reitsma PH. Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2221–2224. [PMC free article] [PubMed]
  • Elder JF, Jr, Turner BJ. Concerted evolution at the population level: pupfish HindIII satellite DNA sequences. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):994–998. [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]
  • Gray IC, Jeffreys AJ. Evolutionary transience of hypervariable minisatellites in man and the primates. Proc Biol Sci. 1991 Mar 22;243(1308):241–253. [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]
  • Hammarström K, Santesson B, Westin G, Pettersson U. The gene cluster for human U2 RNA is located on chromosome 17q21. Exp Cell Res. 1985 Aug;159(2):473–478. [PubMed]
  • Hellmann-Blumberg U, Hintz MF, Gatewood JM, Schmid CW. Developmental differences in methylation of human Alu repeats. Mol Cell Biol. 1993 Aug;13(8):4523–4530. [PMC free article] [PubMed]
  • Hentschel CC. Homocopolymer sequences in the spacer of a sea urchin histone gene repeat are sensitive to S1 nuclease. Nature. 1982 Feb 25;295(5851):714–716. [PubMed]
  • Hipeau-Jacquotte R, Brutlag DL, Brégégère F. Conversion and reciprocal exchange between tandem repeats in Drosophila melanogaster. Mol Gen Genet. 1989 Dec;220(1):140–146. [PubMed]
  • Htun H, Lund E, Dahlberg JE. Human U1 RNA genes contain an unusually sensitive nuclease S1 cleavage site within the conserved 3' flanking region. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7288–7292. [PMC free article] [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]
  • Jackson MS, Mole SE, Ponder BA. Characterisation of a boundary between satellite III and alphoid sequences on human chromosome 10. Nucleic Acids Res. 1992 Sep 25;20(18):4781–4787. [PMC free article] [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]
  • Li YP, Tomanin R, Smiley JR, Bacchetti S. Generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial U2 locus in the human genome. Mol Cell Biol. 1993 Oct;13(10):6064–6070. [PMC free article] [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]
  • Lindgren V, Bernstein LB, Weiner AM, Francke U. Human U1 small nuclear RNA pseudogenes do not map to the site of the U1 genes in 1p36 but are clustered in 1q12-q22. Mol Cell Biol. 1985 Sep;5(9):2172–2180. [PMC free article] [PubMed]
  • Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 1992 Sep 18;70(6):923–935. [PubMed]
  • McCombie WR, Martin-Gallardo A, Gocayne JD, FitzGerald M, Dubnick M, Kelley JM, Castilla L, Liu LI, Wallace S, Trapp S, et al. Expressed genes, Alu repeats and polymorphisms in cosmids sequenced from chromosome 4p16.3. Nat Genet. 1992 Aug;1(5):348–353. [PubMed]
  • Martignetti JA, Brosius J. BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11563–11567. [PMC free article] [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]
  • Miró R, Clemente IC, Fuster C, Egozcue J. Fragile sites, chromosome evolution, and human neoplasia. Hum Genet. 1987 Apr;75(4):345–349. [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]
  • Nag DK, Petes TD. Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation. Mol Cell Biol. 1990 Aug;10(8):4420–4423. [PMC free article] [PubMed]
  • Ono M, Yasunaga T, Miyata T, Ushikubo H. Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J Virol. 1986 Nov;60(2):589–598. [PMC free article] [PubMed]
  • Orr-Weaver TL, Szostak JW. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. [PMC free article] [PubMed]
  • Pesce CG, Rossi MS, Muro AF, Reig OA, Zorzópulos J, Kornblihtt AR. Binding of nuclear factors to a satellite DNA of retroviral origin with marked differences in copy number among species of the rodent Ctenomys. Nucleic Acids Res. 1994 Feb 25;22(4):656–661. [PMC free article] [PubMed]
  • Ried T, Baldini A, Rand TC, Ward DC. Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1388–1392. [PMC free article] [PubMed]
  • Schmid C, Maraia R. Transcriptional regulation and transpositional selection of active SINE sequences. Curr Opin Genet Dev. 1992 Dec;2(6):874–882. [PubMed]
  • Schramayr S, Caporossi D, Mak I, Jelinek T, Bacchetti S. Chromosomal damage induced by human adenovirus type 12 requires expression of the E1B 55-kilodalton viral protein. J Virol. 1990 May;64(5):2090–2095. [PMC free article] [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]
  • Smeets DF, van de Klundert FA. Common fragile sites in man and three closely related primate species. Cytogenet Cell Genet. 1990;53(1):8–14. [PubMed]
  • Smith GP. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. [PubMed]
  • Smith GP. Unequal crossover and the evolution of multigene families. Cold Spring Harb Symp Quant Biol. 1974;38:507–513. [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]
  • Sørensen PD, Lomholt B, Frederiksen S, Tommerup N. Fine mapping of human 5S rRNA genes to chromosome 1q42.11----q42.13. Cytogenet Cell Genet. 1991;57(1):26–29. [PubMed]
  • Strand M, Prolla TA, Liskay RM, Petes TD. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993 Sep 16;365(6443):274–276. [PubMed]
  • Stringer JR. Recombination between poly[d(GT).d(CA)] sequences in simian virus 40-infected cultured cells. Mol Cell Biol. 1985 Jun;5(6):1247–1259. [PMC free article] [PubMed]
  • Sweetser DB, Hough H, Whelden JF, Arbuckle M, Nickoloff JA. Fine-resolution mapping of spontaneous and double-strand break-induced gene conversion tracts in Saccharomyces cerevisiae reveals reversible mitotic conversion polarity. Mol Cell Biol. 1994 Jun;14(6):3863–3875. [PMC free article] [PubMed]
  • Thompson CB. Creation of immunoglobulin diversity by intrachromosomal gene conversion. Trends Genet. 1992 Dec;8(12):416–422. [PubMed]
  • Tlsty TD. Normal diploid human and rodent cells lack a detectable frequency of gene amplification. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3132–3136. [PMC free article] [PubMed]
  • Trask BJ, Hamlin JL. Early dihydrofolate reductase gene amplification events in CHO cells usually occur on the same chromosome arm as the original locus. Genes Dev. 1989 Dec;3(12A):1913–1925. [PubMed]
  • Truss M, Chalepakis G, Beato M. Interplay of steroid hormone receptors and transcription factors on the mouse mammary tumor virus promoter. J Steroid Biochem Mol Biol. 1992 Oct;43(5):365–378. [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]
  • Van Arsdell SW, Weiner AM. Pseudogenes for human U2 small nuclear RNA do not have a fixed site of 3' truncation. Nucleic Acids Res. 1984 Feb 10;12(3):1463–1471. [PMC free article] [PubMed]
  • Warburton PE, Waye JS, Willard HF. Nonrandom localization of recombination events in human alpha satellite repeat unit variants: implications for higher-order structural characteristics within centromeric heterochromatin. Mol Cell Biol. 1993 Oct;13(10):6520–6529. [PMC free article] [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]
  • Westin G, Zabielski J, Hammarström K, Monstein HJ, Bark C, Pettersson U. Clustered genes for human U2 RNA. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3811–3815. [PMC free article] [PubMed]
  • Wevrick R, Willard VP, Willard HF. Structure of DNA near long tandem arrays of alpha satellite DNA at the centromere of human chromosome 7. Genomics. 1992 Dec;14(4):912–923. [PubMed]
  • Wienberg J, Jauch A, Stanyon R, Cremer T. Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization. Genomics. 1990 Oct;8(2):347–350. [PubMed]
  • Wu TC, Lichten M. Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science. 1994 Jan 28;263(5146):515–518. [PubMed]
  • Yunis JJ, Prakash O. The origin of man: a chromosomal pictorial legacy. Science. 1982 Mar 19;215(4539):1525–1530. [PubMed]

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