Human rDNA: evolutionary patterns within the genes and tandem arrays derived from multiple chromosomes.

Human rDNA forms arrays on five chromosome pairs and is homogenized by concerted evolution through recombination and gene conversion (loci RNR1, RNR2, RNR3, RNR4, RNR5, OMIM: 180450). Homogenization is not perfect, however, so that it becomes possible to study its efficiency within genes, within arrays, and between arrays by measuring and comparing DNA sequence variation. Previous studies with randomly cloned genomic DNA fragments showed that different parts of the gene evolve at different rates but did not allow comparison of rDNA sequences derived from specific chromosomes. We have now cloned and sequenced rDNA fragments from specific acrocentric chromosomes to (1) study homogenization along the rDNA and (2) compare homogenization within chromosomes and between homologous and nonhomologous chromosomes. Our results show high homogeneity among regulatory and coding regions of rDNA on all chromosomes, a surprising homogeneity among adjacent distal non-rDNA sequences, and the existence of one to three very divergent intergenic spacer classes within each array.

[1]  J. Dahlberg,et al.  Topology and formation of triple-stranded H-DNA. , 1989, Science.

[2]  C. Polanco,et al.  Multigene family of ribosomal DNA in Drosophila melanogaster reveals contrasting patterns of homogenization for IGS and ITS spacer regions. A possible mechanism to resolve this paradox. , 1998, Genetics.

[3]  V. Funanage,et al.  Assignment of the human dihydrofolate reductase gene to the q11----q22 region of chromosome 5 , 1984, Molecular and cellular biology.

[4]  D. Hickey,et al.  Concerted evolution within a trypsin gene cluster in Drosophila. , 1999, Molecular biology and evolution.

[5]  D. Liao,et al.  Striking bimodal methylation of the repeat unit of the tandem array encoding human U2 snRNA (the RNU2 locus). , 1999, Genomics.

[6]  J. Erickson,et al.  Variation among human 28S ribosomal RNA genes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  N. Arnheim,et al.  The evolutionarily conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during yeast meiosis. , 1986, Molecular and cellular biology.

[8]  GEORGE F. Smith.  Molecular structure of the number 21 chromosome and Down syndrome. , 1985, Annals of the New York Academy of Sciences.

[9]  B. Birshtein,et al.  Nucleotide sequence of an unequal sister chromatid exchange site in a mouse myeloma cell line , 1989, Molecular and cellular biology.

[10]  J. Erickson,et al.  Nucleolus Organizing Genes on Chromosome 21: Recombination and Nondisjunction , 1985, Annals of the New York Academy of Sciences.

[11]  M. Slatkin,et al.  Linkage disequilibrium in human ribosomal genes: implications for multigene family evolution. , 1988, Genetics.

[12]  Christian Schlötterer,et al.  Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests intrachromosomal exchanges drive concerted evolution , 1994, Current Biology.

[13]  L. Hawthorn,et al.  Regional assignment of EST sequences on human chromosome 13. , 1996, Cytogenetics and cell genetics.

[14]  R. Kuick,et al.  Studies of the inheritance of human ribosomal DNA variants detected in two-dimensional separations of genomic restriction fragments. , 1996, Genetics.

[15]  T. Sekiya,et al.  Alteration of Mosaic Methylation of the Repeat Unit of the Human Ribosomal RNA Genes in Lung Cancer , 1999, Biological chemistry.

[16]  P. Hebert,et al.  Gene Conversion and Evolution of Daphniid Hemoglobins (Crustacea, Cladocera) , 1999, Journal of Molecular Evolution.

[17]  P. D’Eustachio,et al.  Human nucleolus organizers on nonhomologous chromosomes can share the same ribosomal gene variants. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Budde,et al.  p53 represses ribosomal gene transcription , 1999, Oncogene.

[19]  D. Irwin,et al.  Mosaic evolution of ruminant stomach lysozyme genes. , 1999, Molecular phylogenetics and evolution.

[20]  A. Weiner,et al.  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. , 1995, Genomics.

[21]  J. Stringer.  Recombination between poly[d(GT).d(CA)] sequences in simian virus 40-infected cultured cells , 1985, Molecular and cellular biology.

[22]  S. Lehnert,et al.  Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. , 1987, Development.

[23]  O. Ryder,et al.  Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Y. Uematsu,et al.  Hotspots of homologous recombination in mammalian genomes , 1987 .

[25]  C. Jones,et al.  Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble). , 1977, American journal of human genetics.

[26]  J. Sylvester,et al.  Complete sequence of the 43-kb human ribosomal DNA repeat: analysis of the intergenic spacer. , 1995, Genomics.

[27]  J. Milner,et al.  Non-activated p53 co-localizes with sites of transcription within both the nucleoplasm and the nucleolus , 2000, Oncogene.

[28]  N. Zini,et al.  Monoclonal antibodies to human DNA topoisomerase I and the two isoforms of DNA topoisomerase II: 170- and 180-kDa isozymes. , 1992, Experimental cell research.

[29]  D. Hillis,et al.  Recombinant DNA sequences generated by PCR amplification. , 1997, Molecular biology and evolution.

[30]  A. Bird,et al.  Mosaic methylation of the repeat unit of the human ribosomal RNA genes. , 1997, Human molecular genetics.

[31]  A. Weiner,et al.  Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion , 1997, The EMBO journal.

[32]  B. Thyagarajan,et al.  Nucleolin Promotes Homologous DNA Pairing in vitro , 1998, Somatic cell and molecular genetics.

[33]  W. P. Wahls,et al.  Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells , 1990, Cell.

[34]  R. Jessberger,et al.  A B-cell-specific DNA Recombination Complex* , 1998, The Journal of Biological Chemistry.

[35]  Jac A. Nickoloff,et al.  Gene Conversion Tracts from Double-Strand Break Repair in Mammalian Cells , 1998, Molecular and Cellular Biology.

[36]  J. Wang,et al.  Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[37]  N. Maizels,et al.  Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[38]  T. Shows,et al.  Organization of rDNA spacer fragment variants among human acrocentric chromosomes in somatic cell hybrids. , 1983, Journal of molecular and applied genetics.