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Results for “genomic tandem array”

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PubMed1995

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.

The RNU2 locus encoding human U2 small nuclear RNA (snRNA) is organized as a nearly perfect tandem array containing 5 to 22 copies of a 5.8-kb repeat unit. Just downstream of the U2 snRNA gene in each 5.8-kb repeat unit lies a large (CT)n.(GA)n dinucleotide repeat (n approximately equal to 70). This form of genomic organization, in which one repeat is embedded within another, provides an unusual opportunity to study the balance of forces maintaining the homogeneity of both kinds of repeats. Using a combination of field inversion gel electrophoresis and polymerase chain reaction, we have been able to study the CT microsatellites within individual U2 tandem arrays. We find that the CT microsatellites within an RNU2 allele exhibit significant length polymorphism, despite the remarkable homogeneity of the surrounding U2 repeat units. Length polymorphism is due primarily to loss or gain of CT dinucleotide repeats, but other types of deletions, insertions, and substitutions are also frequent. Polymorphism is greatly reduced in regions where pure (CT)n tracts are interrupted by occasional G residues, suggesting that irregularities stabilize both the length and the sequence of the dinucleotide repeat. We further show that the RNU2 loci of other catarrhine primates (gorilla, chimpanzee, orangutan, and baboon) contain orthologous CT microsatellites; these also exhibit length polymorphism, but are highly divergent from each other. Thus, although the CT microsatellite is evolving far more rapidly than the rest of the U2 repeat unit, it has persisted through multiple speciation events spanning > 35 Myr. The persistence of the CT microsatellite, despite polymorphism and rapid evolution, suggests that it might play a functional role in concerted evolution of the RNU2 loci, perhaps as an initiation site for recombination and/or gene conversion.

Animals↗

PubMed2001

The pericentromeric heterochromatin of the grass Zingeria biebersteiniana (2n = 4) is composed of Zbcen1-type tandem repeats that are intermingled with accumulated dispersedly organized sequences.

DNA reassociation and hydroxyapatite chromatography were used to isolate high-copy DNA of the grass Zingeria biebersteiniana (2n = 4). In situ hybridization demonstrated that the DNA isolated was enriched for pericentromere-specific repetitive sequences. One abundant pericentromere-specific component is the differentially methylated tandem-repeat family Zbcen1. Other sequences isolated, Zb46 and Zb47A, are dispersed and display similarity to parts of the gypsy- and copia-like retrotransposable elements of other grasses. In situ hybridization with the copia-like sequence Zb47A resulted in dispersed labelling along the chromosome arms, with a significant signal accumulation in the pericentromeric region of all chromosomes. It is concluded that the pericentromeric heterochromatin of Z. biebersteiniana is composed of members of the Zbcen1 tandem repeat family and that these tandem arrays are intermingled with accumulated putative copia-like retrotransposon sequences. An observed Rab1 interphase orientation suggests that the length of the chromosomes rather than the genome size is the determining factor of the Rab1 phenomenon.

Centromere↗

PubMed1993

Heterogeneity in the concerted evolution process of a tandem satellite array in meadow mice (Microtus).

The evolutionary history of a 160-bp tandem satellite array, originally described from Microtus chrotorrhinus and called MSAT-160, was examined in related species of arvicolid rodents by sequence analyses, quantitative dot blotting, and Southern blotting. Results indicate that MSAT-160 is present in 12 of the 20 species and subspecies of Microtus assayed, but not in species belonging to any of the eight other genera examined. DNA from each species containing MSAT-160 was digested with 12 restriction endonucleases and restriction patterns were obtained reflecting the variable extent of homogenization of any given variant in different species. For example, with MboI digestion, M. chrotorrhinus produced a type A ladder pattern where most monomers contain the restriction site, M. ochrogaster generated a type B pattern where most monomers lack the site, and M. agrestis yielded a pattern intermediate between the A and B types. Further, dot blotting revealed copy-number differences between species. These findings indicate that changes in the periodic structure and amount of satellite DNA have occurred since these species last shared a common ancestor. In addition, various species-specific patterns were documented, illustrating that mechanisms other than genome-wide homogenization, such as stochastic mutation, out-of-register crossing over, deletion, and random amplification also play a role in structuring tandem arrays. Stochastic mutation and homogenization rates in satellite DNA, levels of species diversity, and magnitudes of chromosomal divergence differ significantly in Microtus, Mus and Ctenomys, the three rodent lineages examined.

Animals↗

PubMed1990

An alpha satellite DNA polymorphism specific for the centromeric region of chromosome 13.

Alpha satellite DNA is composed of variants of a short consensus sequence that are repeated in tandem arrays in the centromeric heterochromatin of each human chromosome. To define centromeric markers for linkage studies, we screened human genomic DNA for restriction fragment length polymorphisms using a probe detecting alphoid sequences on chromosomes 13 and 21. We describe one such DNA polymorphism. Analysis of linkage of this DNA marker to other polymorphic markers in the CEPH pedigrees demonstrates linkage to markers on the proximal long arm of chromosome 13 and defines the centromeric end of the linkage map of this chromosome.

Blotting, Southern↗

PubMed2002

Evidence for a fast, intrachromosomal conversion mechanism from mapping of nucleotide variants within a homogeneous alpha-satellite DNA array.

Assuming that patterns of sequence variants within highly homogeneous centromeric tandem repeat arrays can tell us which molecular turnover mechanisms are presently at work, we analyzed the alpha-satellite tandem repeat array DXZ1 of one human X chromosome. Here we present accurate snapshots from this dark matter of the genome. We demonstrate stable and representative cloning of the array in a P1 artificial chromosome (PAC) library, use samples of higher-order repeats subcloned from five unmapped PACs (120-160 kb) to identify common variants, and show that such variants are presently in a fixed transition state. To characterize patterns of variant spread throughout homogeneous array segments, we use a novel partial restriction and pulsed-field gel electrophoresis mapping approach. We find an older large-scale (35-50 kb) duplication event supporting the evolutionarily important unequal crossing-over hypothesis, but generally find independent variant occurrence and a paucity of potential de novo mutations within segments of highest homogeneity (99.1%-99.3%). Within such segments, a highly nonrandom variant clustering within adjacent higher-order repeats was found in the absence of haplotypic repeats. Such variant clusters are hardly explained by interchromosomal, fixation-driving mechanisms and likely reflect a fast, localized, intrachromosomal sequence conversion mechanism.

Animals↗

PubMed2000

Genomic organization of the family of CNR cadherin genes in mice and humans.

The cadherin-related neuronal receptor (CNR) family is localized to the synaptic junction, and their cytoplasmic domains interact with Fyn-tyrosine kinase. Here, we describe the chromosomal locations and the orthologous genomic structures of CNR family members in mice and humans. In the genomic organization, distinct exons, each of which encodes the N-terminus of a different CNR ("variable region"), are clustered in a tandem array, and these exons are spliced to a common region composed of three exons ("constant region"). We also discovered three alternative versions of the transcripts; a single variable exon connects with three different C-terminal tails, comparable to class-switching in the immunoglobulin heavy chain. Thus the CNR family in the central nervous system has similarities to the immunoglobulin and T-cell receptor genes in the immune system.

Amino Acid Sequence↗

PubMed1990

Telomere-related sequences at interstitial sites in the human genome.

The ends (telomeres) of eukaryotic chromosomes are protected from degradation and from loss during DNA replication by buffers of simple tandem repetitive sequence. The nucleotide sequence of these telomeric arrays is fundamental to telomere function as a site for protein and ribonucleoprotein binding and varies only slightly in a wide range of organisms. We present evidence that arrays of this human telomeric sequence, TTAGGG, are present not only at the ends of human chromosomes but also at numerous interstitial sites. These interstitial loci share nucleotide sequence similarity outside the repetitive array, suggesting that they are related functionally or have evolved from a common progenitor locus.

Base Sequence↗

PubMed1994

High resolution fluorescence in situ hybridization to linearly extended DNA visually maps a tandem repeat associated with facioscapulohumeral muscular dystrophy immediately adjacent to the telomere of 4q.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder. The FSHD locus has been linked to the most distal genetic markers on the long arm of chromosome 4. An EcoRI fragment length polymorphism segregates with the disease in most FSHD families. Within the EcoRI fragment lies a tandem array of 3.2 kb repeats. Deletions of integral copies of this repeat have been associated with the disease. The 3.2 kbp repeat has recently been shown to cross-hybridize to several regions of heterochromatin in the human genome and DNA sequence analysis reveals strong homology to a class of heterochromatin repeats, LSau. In this report, we demonstrate that the 3.2 kbp tandem repeat lies adjacent to a subtelomeric sequence, which is within 5-14 kb of the telomeric repeat (TTAGGG)n. Direct visual fluorescence hybridization to linearly extended strands of DNA enabled the visualization of this subtelomeric sequence as a short string of signals at the end of a longer string of signals from the differentially labeled 3.2 kbp tandem repeat. Furthermore, in support of our data showing that the 3.2 kbp repeat lies in close proximity to the telomere of 4q, we demonstrated the lack of hybridization of total human DNA to this same region. Our results indicate that the tandem array of 3.2 kbp repeats, disrupted in FSHD, lies immediately adjacent to the telomere of 4q and that the gene responsible for FSHD is likely located proximal to the tandem repeat.

Animals↗

PubMed1989

Stable maintenance of a 35-base-pair yeast mitochondrial genome.

Small deletion variants ([rho-] mutants) derived from the wild-type ([ rho+]) Saccharomyces cerevisiae mitochondrial genome were isolated and characterized. The mutant mitochondrial DNAs (mtDNAs) examined retained as little as 35 base pairs of one section of intergenic DNA, were composed entirely of A.T base pairs, and were stably maintained. These simple mtDNAs existed in tandemly repeated arrays at an amplified level that made up approximately 15% of the total cellular DNA and, as judged by fluorescence microscopy, had a nearly normal mitochondrial arrangement throughout the cell cytoplasm. The simple nature of these [rho-] genomes indicates that the sequences required to maintain mtDNA must be extremely simple.

Base Sequence↗

PubMed1983

Two distant clusters of partially homologous small repeats of Epstein-Barr virus are transcribed upon induction of an abortive or lytic cycle of the virus.

The two regions of the Epstein-Barr virus genome carrying partially homologous clusters of short tandem repeats (DSL and DSR [duplicated sequences, left and right, respectively] ) are transcribed into polyadenylated RNA upon spontaneous or chemical induction of the lytic virus cycle. In Raji, an Epstein-Barr virus genome carrying a nonproducer cell line, transcription of DSL and DSR is only observed upon induction of an abortive life cycle of the virus. In the nonproducer cell line Raji, the polyadenylated transcripts of DSL and DSR are about 2,500 and 2,700 bases, respectively, in length. Four different spontaneous Epstein-Barr virus producer lines, M-ABA, CC34-5, QIMR-WIL, and B95-8, differ in the length of their DSL and/or DSR regions by different numbers of tandem repeats. The size of the RNAs corresponds in all cases to the size of the respective cluster of repeats, indicating that a large part of each RNA species is colinearly transcribed from the entire tandem repeat arrays. Both the DSL and the DSR RNAs have the same polarity proceeding from right to left on the Epstein-Barr virus genome. DNA sequence analysis of the DSR repeat revealed that translation of the RNA would be possible in three open reading frames within the repeat cluster. Short homologies to herpes simplex virus IR-TR sequences and to immunoglobulin switch region sequences (IgH-S) are discussed.

Base Sequence↗

PubMed1998

Identification of two Krüppel-related zinc finger genes (ZNF200 and ZNF210) from human chromosome 16p13.3.

During the course of cloning the gene for familial Mediterranean fever (FMF), we identified a number of transcripts from a 275-kb genomic region on 16p13.3. Two of the transcripts were found to contain multiple C2H2-type zinc finger motifs in tandem arrays, indicating that they are members of the Krüppel-type family. One transcript was found to be an alternatively spliced form of a previously reported zinc finger gene, ZNF200. The other transcript, ZNF210, is 2017 bp and encodes an open reading frame of 504 aa. Northern blot analysis indicates that ZNF210 is expressed in all the tissues tested with the highest expression in heart, skeletal muscle, pancreas, prostate, ovary, and colon. On the other hand, the strongest expression of ZNF200 is in testis, with very low levels in all the other tissues tested. Sequence analysis reveals eight C2H2 zinc finger motifs at the C-terminus of ZNF210 and five in ZNF200. In addition, ZNF210 also possesses a Krüppel-associated box at its N-terminus, indicating that it might function as a transcription repressor. The intron-exon structures of both genes were determined and showed that ZNF210 has seven exons while the coding part of ZNF200 is distributed in four exons. The locations of ZNF200 and ZNF210 are 10 and 120 kb telomeric to the FMF gene, respectively.

Amino Acid Sequence↗

PubMed1995

Peripherin gene is linked to keratin 18 gene on human chromosome 12.

Peripherin is a neuron-specific intermediate filament (IF) protein, found primarily in phylogenetically old regions of the nervous system. Whereas other neuronal IF genes have only two to three introns and are scattered in the genome, the peripherin gene (PRPH) has a complex intron-exon structure like nonneuronal IF genes that are clustered in tandem arrays, e.g., those encoding the keratins. We used a cosmid containing the human peripherin gene (PRPH) to determine its chromosomal location in relationship to nonneuronal IF genes. Using a rodent-human mapping panel, we localized the PRPH gene to human chromosome 12. Since a cluster of keratin genes maps to 12q12-13, polymorphic markers were developed for PRPH and for one of the keratin genes presumed to be in the cluster, keratin 18 (KRT18). Both markers were typed in CEPH reference families. Pairwise and multipoint analyses of the CEPH data revealed that KRT18 is tightly linked to DNA markers D12S4, D12S22, D12S90, D12S96 and D12S103, which lie between D12S18 and D12S8, with odds greater than 1000:1. These markers are physically located at 12q11-13, thus supporting the fine localization of KRT18 in or near the group of type II keratins in this region. Furthermore, linkage analysis showed that the peripherin gene (PRPH) is tightly linked to KRT18 (Z = 15.73, theta = 0.013), and therefore appears to be in close proximity to the cluster.

Base Sequence↗

PubMed1991

Homologous recombination in the tandem calmodulin genes of Trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification.

Homologous recombination between a calmodulin-neomycin-resistance fusion gene and the Trypanosoma brucei chromosome takes place not only in the large 5'- and 3'-flanking segments of the calmodulin locus but also in any of the four tandem genomic calmodulin genes. This results in a recombined locus consisting of the chimeric neor gene and four, three, two, one, or zero functional calmodulin genes. Cells bearing this latter event have half of their normal number of intact calmodulin genes and an accompanying phenotype of slow growth. Over months of propagation, these lines acquire additional calmodulin genes, frequently by amplifying a calmodulin gene at the untargeted locus, and concomitantly revert to normal growth rate. This response could be related to the property of the trypanosome of maintaining most housekeeping genes in tandem chromosomal arrays. Recombination appears to be initiated by a crossover event between the linearized end of the transfecting plasmid and a homologous region in the host genome; the second crossover generally occurs internally and in that region requires no more than 87 bp of homology.

Animals↗

PubMed1996

Evolution of the gonosomal heterochromatin of Microtus agrestis: rapid amplification of a large, multimeric, repeat unit containing a 3.0-kb (GATA)11-positive, middle repetitive element.

The sex chromosomes of Microtus agrestis are extremely large due to the accumulation of constitutive heterochromatin. We have cloned and characterized a 2,999-bp (GATA)n-positive sequence, following HaeIII digestion, that is confined to the noncentromeric heterochromatin of the X chromosome. The cloned element exhibits an accumulation of certain oligomers, which are scattered throughout its entire length, and several copies of Chi-related sequence motifs, which are thought to be implicated in recombination. The latter might have been responsible for the extensive amplification of homologous genomic elements. The sequence has been amplified to a copy number of 1-2 x 10(4) within the genome of M. agrestis. In contrast to many satellite DNAs, which are thought to be an inevitable constituent of constitutive heterochromatin, the sequence exhibits a tissue-specific methylation pattern and is organized, not as a simple tandem array, but as a component of an extremely large, multimeric, higher-order repeat unit with a length of over 20 kb. This higher-order repeat accounts for at least 15-30% of the gonosomal heterochromatin in M. agrestis. Sequences homologous to pMAHAE2 are abundant in the genomes of all Microtus species. The copy number varies from approximately 100 per diploid genome in M. arvalis, M. oeconomus, and M. cabrerae to approximately 500 per diploid genome in M. guentheri and up to 1-2 x 10(4) in M. agrestis. Our molecular data indicate that the sequences of the pMAHAE2 family probably arose during the evolution of the common ancestor of Microtus and have subsequently been amplified extensively in the X chromosomes of M. agrestis in the phylogenetically very short period of less than 1 million years.

Animals↗

PubMed2003

Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation.

A large family of neural protocadherin (Pcdh) proteins is encoded by three closely linked mammalian gene clusters (alpha, beta, and gamma). Pcdh alpha and gamma clusters have a striking genomic organization. Specifically, each "variable" exon is spliced to a common set of downstream "constant" exons within each cluster. Recent studies demonstrated that the cell-specific expression of each Pcdh gene is determined bya combination of variable-exon promoter activation and cis-splicing of the corresponding variable exon to the first constant exon. To determine whether there are other similarly organized gene clusters in mammalian genomes, we performed a genome-wide search and identified a large number of mammalian genes containing multiple variable first exons. Here we describe several clusters that contain about a dozen variable exons arrayed in tandem, including UDP glucuronosyltransferase (UGT1), plectin, neuronal nitric oxide synthase (NOS1), and glucocorticoid receptor (GR) genes. In all these cases, multiple variable first exons are each spliced to a common set of downstream constant exons to generate diverse functional mRNAs. As an example, we analyzed the tissue-specific expression profile of the mouse UGT1 repertoire and found that multiple isoforms are expressed in a tissue-specific manner. Therefore, this variable and constant genomic organization provides a genetic mechanism for directing distinct cell- and tissue-specific patterns of gene expression.

Animals↗

PubMed1989

Primate evolution of a human chromosome 1 hypervariable repetitive element.

The clone designated hMF #1 represents a clustered DNA family, located on chromosome 1, consisting of tandem arrays displaying a monomeric length of 40 bp and a repetition frequency of approximately 7 x 10(3) copies per haploid genome. The sequence hMF #1 reveals multiple restriction fragment length polymorphisms (RFLPs) when human genomic DNA is digested with a variety of 4-6-bp recognition sequence restriction enzymes (i.e., Taq I, Eco RI, Pst I, etc.). When hamster and mouse genomic DNA was digested and analyzed, no cross-species homology could be observed. Further investigation revealed considerable hybridization in the higher primates (chimpanzee, gorilla, and orangutan) as well as some monkey species. The evolutionary relationship of this repetitive DNA sequence, found in humans, to that of other primates was explored using two hybridization methods: DNA dot blot to establish copy number and Southern DNA analysis to examine the complexity of the RFLPs. Homology to the hMF #1 sequence was found throughout the suborder Anthropoidea in 14 ape and New and Old World monkey species. However the sequence was absent in one species of the suborder Prosimii. Several discrepancies between "established" evolutionary relationships and those predicted by hMF #1 exist, which suggests that repetitive elements of this type are not reliable indicators of phylogenetic branching patterns. The phenomenon of marked diversity between sequence homologies and copy numbers of dispersed repetitive DNA of closely related species has been observed in Drosophila, mice, Galago, and higher primates. We report here a similar phenomenon for a clustered repeat that may have originated at an early stage of primate evolution.

Animals↗

PubMed1984

Distinctive termini characterize two families of human endogenous retroviral sequences.

Human DNA contains many copies of endogenous retroviral sequences. Characterization of molecular clones of these structures reveals the existence of two related families. One family consists of full-length (8.8 kilobases) proviral structures, with typical long terminal repeates (LTR's). The other family consists of structures, which contain only 4.1 kilobases of gag-pol sequences, bounded by a tandem array of imperfect repeats 72 to 76 base pairs in length. Typical LTR sequences that exist as solitary elements in the genome were cloned and characterized.

Base Sequence↗

PubMed1995

Repetitive DNA sequence families in Hemitaxonus minomensis and H. athyrii (Hymenoptera; Tenthredinidae).

Families of the repetitive DNA sequences from Hemitaxonus minomensis and H. athyrii were characterized. pHMS family and pHME family in H. minomensis consist of tandemly arranged arrays whose basic repeat units are 260 bp and 330 bp, respectively. pHAE family in H. athyrii consists of a tandemly arranged array whose basic repeat unit is 330 bp. pHMS family and pHME family occupy approximately 4.8% and 0.07% of the genome of H. minomensis, respectively. By contrast, in H. athyrii, pHAE family comprise 0.04% of the genome. Nucleotide sequence comparison of these three repetitive families showed very little homology. Southern blot hybridization using six species of Hemitaxonus showed that these repetitive families are species specific.

Animals↗