DOCSLIB.ORG

The Evolution of Tandemly Repetitive DNA: Recombination Rules

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Evolution of Tandemly Repetitive DNA: Recombination Rules Copyright 0 1992 by the Genetics Societyof America The Evolution of Tandemly Repetitive DNA: Recombination Rules Rosalind M. Harding,* A. J. Boyce? andJ. B. Clegg* *MRC MolecularHaematology Unit, Institute of Molecular Medicine, University of Oxford, JohnRadcliffe Hospital, Headington, Oxford OX3 SOU, England, and ?Department of Biological Anthropology, University of Oxford, Oxford OX2 64S, England Manuscript received April 3, 1992 Accepted for publication August 3, 1992 ABSTRACT Variable numbers of tandem repeats (VNTRs), which include hypervariable regions, minisatellites and microsatellites, can be assigned together with satellite DNAs to define a class of noncoding tandemly repetitive DNA (TR-DNA). The evolution of TR-DNA is assumed to be driven by an unbiased recombinational process.A simulation modelof unequal exchange is presented and used to investigate the evolutionary persistence of single TR-DNA lineages. Three different recombination rules are specified to govern the expansion and contraction of a TR-DNA lineage from an initial array of two repeats to, finally, a single repeat allele, which cannot participate in a misalignment and exchange process. In the absence of amplification or selection acting to bias array evolution toward expansion, the probability of attaining a target array size is a function only of the initial number of repeats. Weshow that the proportions oflineages attaining a targeted array size are the same irrespective of recombination rule and rate, demonstrating that our simulation modelis well behaved. The time takento attain a target array size, the persistence of the target array, and the total persistence time of repetitive array structure,are functions of the initial number of repeats, the rate of recombination, and the rules of misalignment preceding recombinational exchange. These relation- ships are investigated usingour simulation model. While misalignmentcontraint is probably greatest for satellite DNA it also seems important in accounting for the evolution of VNTR loci including minisatellites. This conclusion is consistent with the observed nonrandom distributions of VNTRs and other TR-DNAs in the human genome. ONCODINGDNA sequenceswith “variable VNTRs to be examined within a context of TR-DNA N numbers of tandem repeats,” termed VNTRs, evolution. includethose loci called hypervariableregions The evolution of TR-DNA can be viewed within (HVRs), minisatellites and microsatellites. Grouping the even broader contextof the evolution of repetitive VNTRs together with satellite DNA creates a class of DNA, for which there area large numberof analytical noncoding tandemly repetitive DNA, hereafter de- and simulation models. Much attention has beengiven noted as TR-DNA. Satellite TR-DNA regions may to the evolutionary forces acting on multigenefamilies also have variable numbers of tandem repeats, but (HARDISON199 1 ; HUGHES199 1 ; LOOMISand GILPIN this is difficult todetermine. Because VNTRs are 1986; MAEDA and SMITHIES1986) andon inter- extensively polymorphic they can be used to address spersed repeats such as transposable elements(CHAR- a wide range of problems in forensicscience (JEFFREYS LESWORTH and LANGLEY1991; MARUYAMAand et al. 199 l), the determination of family relationships HARTL1991), SINES and LINES (BUCHETON1990; (JEFFREYS, TURNERand DEBENHAM1991), human SINGER 1982; ZUCKERKANDL, LATTER and JURKA gene mapping (NAKAMURAet al. 1987), and popula- 1989). Questionsabout the evolution of repetitive tion genetics (BAIRDet al. 1986; BALAZSet al. 1989; DNA haveaddressed two broad issues. First, how CHAKRABORTYet al. 1991 ; DEKA,CHAKRABORTY and does recombinational exchange resolving as genecon- FERRELL199 1; FLINTet al. 1989). The many appli- version,promote the evolutionary persistence and cations of VNTR loci rest on assumptions about their spreading of particular repeat lineages across the ge- evolutionary dynamics.Interestingly, a minisatellite nome of a species (NAGYLAKIand PETES1982; NA- VNTR modelpresented by GRAY and JEFFREYS GYLAKI 1984a,b, 1990; OHTA 1978, 1989; OHTA and (199 1) seems to sit at odds with general models for DOVER 1983)? Second,what processesof unequal TR-DNA, developed before the explosion of interest exchange promoteor control the variationin numbers in VNTRs. Are VNTRs, minisatellites in particular, of repeats within lineages (KRUGERand VOGEL1975; qualitatively different from otherTR-DNAs? The aim PERELSONand BELL 1977; SMITH1976; TAKAHATA of the study reported here is to review the biology of 1981)? The studies addressing the second question TR-DNA, in particular the VNTR loci, and on this are pertinent to the developmenta TR-DNA of model foundation, build a simulation model which enables which can account for VNTR dynamics. Genetics 132: 847-859 (November, 1992) 848 R. M. Harding, A. J. Boyce and J. B. Clegg A major aim of these earlier theoretical studies was This model is shown to be compatible with the expan- to determine the balance of evolutionary forces per- sion times of two minisatellite VNTRs in humans from mitting the accumulation and stabilization of large homologous TR-DNA loci in a primate ancestor.The arrays ofrepeats. The dual parametersof genetic drift justification for this model is that, while the probabil- and unequal exchange, unbiased toward array expan- ity of generating a large and hypervariable tandem sion by amplification or selection, cannot account for array at any particular locus is small, given the vast equilibrium distributions of large numbers of repeats number of potential TR-DNA lociin the genome, (WALSH1987). Amplification is ageneralized term many arrays should be large. for any mutational process that expands DNA length. We mean by unequal exchange a mutational process BIOLOGICALBACKGROUND TO ATR-DNA of recombination either between homologous chro- MODEL mosomes or within chromosomes between sister chro- matids. To counteract the loss of repeats by drift and Structure: Minisatellite DNA, HVRs andother unequal exchange it is necessary to posit a balancing VNTRs, including simple-sequence or microsatellite rate of amplification or positive selection. Unless these DNA (TAUTZ1989; WEBERand MAY 1989)share evolutionary forces are ongoing, the probability of commonstructural features with highly repeated finding a large tandem array at a potential TR-DNA DNA such as telomeric (BLACKBURN 1990; 199 1) and locus is low. Selection is important in studies applica- satellite (WILLARDand WAYE 1987)sequences. Their ble to multigene families (TAKAHATA1981), as is similarities suggest that these DNAs are subject to the amplification in those of transposable elements and same generalevolutionary processes of recombina- retroposons(CHARLESWORTH and LANGLEY 199 1). tional mutation. Within this class of polymorphic non- Either selection or amplification, or both, have also coding TR-DNA loci, however, there is a range of been incorporated into evolutionary models of TR- repeatunit size andnumber. The oligonucleotide repeat unit sequences of several to tens of base pairs DNA lineages to account forthe accumulation of large UEFFREYS, WILSONand THEIN1985; WoNG et al. stable tandem arraysof satellite DNA (STEPHAN1986, 1987) in minisatellite loci are shorter than thetypical 1987, 1989; WALSH1987). An important conclusion motifs of satellite DNA (SINGER 1982), but larger than of these analyses is that the evolutionary persistence the di- and trinucleotide repeats of microsatellite loci, of large arrays critically depends on balancea between such as CA repeats (TAUTZ1989). Also, the average a moderate, or at least equivalent, rate of amplifica- copy numbers per minisatellite allele in the tens to tion relative to a low rate of unequal exchange. hundreds are intermediatebetween the thousandfold GRAY andJEFFREYS (1991) have alternatively em- copies of satellite sequences and the few copies com- phasized that sufficient rates of amplification may be prizing amicrosatellite allele. This structuralvariation low, even when rates of unequal exchange are high. among TR-DNAs points to differences in the recom- In their model for the evolutionary dynamics of a binational rules acting on them. minisatellite, MS32, amplification is simulated as a Rules and rates of recombination: Recombination duplication of uniquesequence creating an initial of minisatellite alleles probably occurs during, or after array of two tandem repeats. The dynamics subse- replication, as DNA slippage or unequal sister chro- quent to the single amplification event are modeled matid exchange (USCE). The evidence against a role as a random walk via a path of unbiased array expan- for homologous recombination within minisatellite sion and contraction to a single repeat evolutionary arraysderives from the nonrandom association of dead end.Rates of unequal exchangeare proportional minisatellite alleles on different haplotypes. This has to allele size and ordersof magnitude higher than the been observed for the insulin 5’HVR (ROTWEINet al. low rates determined for stable, persistent TR-DNA 1986), the VNTRlocus, YNZ22 (WOLFF,NAKAMURA by analytical modeling (WALSH1987). Since there is and WHITE 1988), theminisatellite (MS 1) locus, D S71 a moderate probability (in the range of 0.001-0.05) (WOLFFet al. 1989), the HRAS1 3’VNTR (KASPER- that a long sequence of unequal exchange events is CZYK, DIMARTINOand KRONTIRIS1990) anda-globin initiated by a single duplication, it seems that a low 3‘HVR alleles (MARTINSON1991). On the other hand, rate of amplification is sufficient. In this model, short
Load more

Recommended publications
  • Staphylococcus Aureus Cas9 for Simultaneous
    Published online 5 January 2016 Nucleic Acids Research, 2016, Vol. 44, No. 8 e75 doi: 10.1093/nar/gkv1533 Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci Baohui Chen1, Jeffrey Hu1, Ricardo Almeida2, Harrison Liu3, Sanjeev Balakrishnan4, Christian Covill-Cooke5, Wendell A. Lim2,6 and Bo Huang1,7,* 1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA, 2Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA, 3Graduate Program of Bioengineering, University of California, San Francisco, San Francisco, CA 94143, USA, 4Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA, 5MRC Laboratory of Molecular Cell Biology, University College London, London, WC1E 6BT, UK, 6Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 4143, USA and 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA Received August 20, 2015; Revised November 24, 2015; Accepted December 22, 2015 ABSTRACT fold that interacts with Cas9 (15–18). Target recognition by the Cas9-sgRNA complex requires Watson–Crick base In order to elucidate the functional organization of pairing with the 5 end of the sgRNA (≈20 nt) as well as the genome, it is vital to directly visualize the interac- a short protospacer-adjacent motif (PAM) located imme- tions between genomic elements in living cells. For diately downstream of the target DNA sequence (13,19– this purpose, we engineered the Cas9 protein from 21). The PAM sequences are diverse among orthologous Staphylococcus aureus (SaCas9) for the imaging of CRISPR-Cas systems.
    [Show full text]
  • Retrotransposon- and Microsatellite Sequence-Associated Genomic Changes in Early Generations of a Newly Synthesized Allotetraploid Cucumis 3 Hytivus Chen & Kirkbride
    Plant Mol Biol DOI 10.1007/s11103-011-9804-y Retrotransposon- and microsatellite sequence-associated genomic changes in early generations of a newly synthesized allotetraploid Cucumis 3 hytivus Chen & Kirkbride Biao Jiang • Qunfeng Lou • Zhiming Wu • Wanping Zhang • Dong Wang • Kere George Mbira • Yiqun Weng • Jinfeng Chen Received: 27 May 2011 / Accepted: 27 June 2011 Ó Springer Science+Business Media B.V. 2011 Abstract Allopolyploidization is considered an essential generations of a newly synthesized allotetraploid Cucum- evolutionary process in plants that could trigger genomic is 9 hytivus Chen & Kirkbride (2n = 4x = 38) which was shock in allopolyploid genome through activation of tran- derived from crossing between cultivated cucumber scription of retrotransposons, which may be important in C. sativus L. (2n = 2x = 14) and its wild relative C. hystrix plant evolution. Two retrotransposon-based markers, inter- Chakr. (2n = 2x = 24). Extensive genomic changes were retrotransposon amplified polymorphism and retro- observed, most of which involved the loss of parental DNA transposon-microsatellite amplified polymorphism and a fragments and gain of novel fragments in the allotetraploid. microsatellite-based marker, inter simple sequence repeat Among the 28 fragments examined, 24 were lost while four were employed to investigate genomic changes in early were novel, suggesting that DNA sequence elimination is a relatively frequent event during polyploidization in Cucumis. Interestingly, of the 24 lost fragments, 18 were of C. hystrix origin, four were C. sativus-specific, and the Electronic supplementary material The online version of this remaining two were shared by both species, implying that article (doi:10.1007/s11103-011-9804-y) contains supplementary material, which is available to authorized users.
    [Show full text]
  • Frequent Homozygous Deletions in the FRA3B Region in Tumor Cell Lines Still Leave the FHIT Exons Intact
    Oncogene (1998) 16, 635 ± 642 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact Liang Wang1, John Darling1, Jin-San Zhang1, Chi-Ping Qian1, Lynn Hartmann2, Cheryl Conover2, Robert Jenkins1 and David I Smith1 1Division of Experimental Pathology, Department of Laboratory Medicine and Pathology; and 2Department of Medical Oncology, Mayo Clinic/Foundation, 200 First Street, SW, Rochester, Maine 55902, USA FRA3B at human chromosomal band 3p14.2 is the most Soreng, 1984). However, whether or not fragile sites active common fragile site in the human genome. The play a causative role in these structural chromosome molecular mechanism of fragility at this region remains alterations has yet to be determined. unknown but does not involve expansion of a trinucleo- FRA3B, at chromosome band 3p14.2, is the most tide or minisatellite repeat as has been observed for highly inducible fragile site in the human genome several of the cloned rare fragile sites. Deletions and (Smeets et al., 1986). The constitutive familial renal cell rearrangements at FRA3B have been observed in a carcinoma-associated translocation t(3;8)(p14.2;q24) number of distinct tumors. The recently identi®ed (hRCC) (Cohen et al., 1979) was localized immedi- putative tumor suppressor gene FHIT spans FRA3B, ately centromeric of FRA3B (Paradee et al., 1995; and various groups have reported identifying deletions in Boldog et al., 1993). Structural rearrangements and this gene in dierent tumors. Using a high density of deletions at FRA3B were reported in a variety of PCR ampli®able markers within FRA3B searching for histologically dierent cancers including lung (Todd et deletions in the FRA3B region, we have analysed 21 al., 1997), breast (Panagopoulos et al., 1996), tumor cell lines derived from renal cell, pancreatic, and esophageal (Wang et al., 1996), ovarian (Ehlen et al., ovarian carcinomas.
    [Show full text]
  • Young, L.J., & Hammock E.A.D. (2007)
    Update TRENDS in Genetics Vol.23 No.5 Research Focus On switches and knobs, microsatellites and monogamy Larry J. Young1 and Elizabeth A.D. Hammock2 1 Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, 954 Gatewood Road, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA 2 Vanderbilt Kennedy Center and Department of Pharmacology, 465 21st Avenue South, MRBIII, Room 8114, Vanderbilt University, Nashville, TN 37232, USA Comparative studies in voles have suggested that a formation. In male prairie voles, infusion of vasopressin polymorphic microsatellite upstream of the Avpr1a locus facilitates the formation of partner preferences in the contributes to the evolution of monogamy. A recent study absence of mating [7]. The distribution of V1aR in the challenged this hypothesis by reporting that there is no brain differs markedly between the socially monogamous relationship between microsatellite structure and mon- and socially nonmonogamous vole species [8]. Site-specific ogamy in 21 vole species. Although the study demon- pharmacological manipulations and viral-vector-mediated strates that the microsatellite is not a universal genetic gene-transfer experiments in prairie, montane and mea- switch that determines mating strategy, the findings do dow voles suggest that the species differences in Avpr1a not preclude a substantial role for Avpr1a in regulating expression in the brain underlie the species differences in social behaviors associated with monogamy. social bonding among these three closely related species of vole [3,6,9,10]. Single genes and social behavior Microsatellites and monogamy The idea that a single gene can markedly influence Analysis of the Avpr1a loci in the four vole species complex social behaviors has recently received consider- mentioned so far (prairie, montane, meadow and pine voles) able attention [1,2].
    [Show full text]
  • Evaluating the Probability of CRISPR-Based Gene Drive Contaminating Another Species
    bioRxiv preprint doi: https://doi.org/10.1101/776609; this version posted September 19, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species 1 2 3 4 Virginie Courtier-Orgogozo ,​ Antoine Danchin ,​ Pierre-Henri Gouyon ​ and Christophe Boëte ​ ​ ​ ​ 1 I​ nstitut Jacques Monod, CNRS, UMR 7592, Université de Paris, Paris, France 2 I​ nstitut Cochin INSERM U1016 – CNRS UMR8104 – Université Paris Descartes, Paris, France 3 I​ nstitut de Systématique, Évolution, Biodiversité, Muséum National d'Histoire Naturelle, CNRS, Sorbonne Université, EPHE, UA, Paris, France 4 I​ SEM, Université de Montpellier, CNRS, IRD, EPHE, Montpellier, France Abstract The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct with ​ ​ hyb = probability of hybridization between the target species and a non-target species ​ transf = probability of horizontal transfer of a piece of DNA containing the gene drive ​ cassette from the target species to a non-target species (with no hybridization) express = probability that the Cas9 and guide RNA genes are expressed ​ ​ ​ cut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the ​ new host flank = probability that the gene drive cassette inserts at the cut site ​ immune = probability that the immune system does not reject Cas9-expressing cells ​ ​ ​ nonextinct = probability of invasion of the drive within the population ​ We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans.
    [Show full text]
  • Evaluation of the Effects of Sequence Length and Microsatellite Instability
    Int. J. Biol. Sci. 2019, Vol. 15 2641 Ivyspring International Publisher International Journal of Biological Sciences 2019; 15(12): 2641-2653. doi: 10.7150/ijbs.37152 Research Paper Evaluation of the effects of sequence length and microsatellite instability on single-guide RNA activity and specificity Changzhi Zhao1*, Yunlong Wang2*, Xiongwei Nie1, Xiaosong Han1, Hailong Liu1, Guanglei Li1, Gaojuan Yang1, Jinxue Ruan1, Yunlong Ma1, Xinyun Li1, 3, Huijun Cheng1, Shuhong Zhao1, 3, Yaping Fang2, Shengsong Xie1, 3 1. Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, P. R. China; 2. Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China; 3. The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, P. R. China. *The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Corresponding authors: Shengsong Xie, Tel: 086-027-87387480; Fax: 086-027-87280408; Email: [email protected]; Yaping Fang, Tel: 86-28-87285078; Fax: 86-28-87284285; Email: [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.07.21; Accepted: 2019.09.02; Published: 2019.10.03 Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology is effective for genome editing and now widely used in life science research.
    [Show full text]
  • Repetitive Elements in Humans
    International Journal of Molecular Sciences Review Repetitive Elements in Humans Thomas Liehr Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, D-07747 Jena, Germany; [email protected] Abstract: Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well. Keywords: variable numbers of tandem repeats (VNTRs); microsatellites; minisatellites; small-scale repetitive elements (SSREs); chromosomal heteromorphisms (CHs); higher-order repeat (HOR); retroviral DNA 1. Introduction Citation: Liehr, T. Repetitive In humans, like in other higher species, the genome of one individual never looks 100% Elements in Humans. Int. J. Mol. Sci. alike to another one [1], even among those of the same gender or between monozygotic 2021, 22, 2072.
    [Show full text]
  • Genome Organization/ Human
    Genome Organization/ Secondary article Human Article Contents . Introduction David H Kass, Eastern Michigan University, Ypsilanti, Michigan, USA . Sequence Complexity Mark A Batzer, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA . Single-copy Sequences . Repetitive Sequences . The human nuclear genome is a highly complex arrangement of two sets of 23 Macrosatellites, Minisatellites and Microsatellites . chromosomes, or DNA molecules. There are various types of DNA sequences and Gene Families . chromosomal arrangements, including single-copy protein-encoding genes, repetitive Gene Superfamilies . sequences and spacer DNA. Transposable Elements . Pseudogenes . Mitochondrial Genome Introduction . Genome Evolution . Acknowledgements The human nuclear genome contains 3000 million base pairs (bp) of DNA, of which only an estimated 3% possess protein-encoding sequences. As shown in Figure 1, the DNA sequences of the eukaryotic genome can be classified sequences such as the ribosomal RNA genes. Repetitive into several types, including single-copy protein-encoding sequences with no known function include the various genes, DNA that is present in more than one copy highly repeated satellite families, and the dispersed, (repetitive sequences) and intergenic (spacer) DNA. The moderately repeated transposable element families. The most complex of these are the repetitive sequences, some of remainder of the genome consists of spacer DNA, which is which are functional and some of which are without simply a broad category of undefined DNA sequences. function. Functional repetitive sequences are classified into The human nuclear genome consists of 23 pairs of dispersed and/or tandemly repeated gene families that chromosomes, or 46 DNA molecules, of differing sizes either encode proteins (and may include noncoding (Table 1).
    [Show full text]
  • MNS16A Tandem Repeat Minisatellite of Human Telomerase Gene: Functional Studies in Colorectal, Lung and Prostate Cancer
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 17), pp: 28021-28027 Research Paper MNS16A tandem repeat minisatellite of human telomerase gene: functional studies in colorectal, lung and prostate cancer Philipp Hofer1, Cornelia Zöchmeister1, Christian Behm1, Stefanie Brezina1, Andreas Baierl2, Angelina Doriguzzi1, Vanita Vanas1, Klaus Holzmann1, Hedwig Sutterlüty- Fall1, Andrea Gsur1 1Medical University of Vienna, Institute of Cancer Research, A-1090 Vienna, Austria 2University of Vienna, Department of Statistics and Operations Research, A-1010 Vienna, Austria Correspondence to: Andrea Gsur, email: [email protected] Keywords: genetic variation, MNS16A, functional polymorphism, telomerase, TERT regulation Received: September 23, 2016 Accepted: February 21, 2017 Published: March 03, 2017 Copyright: Hofer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity. For the first time, we investigated promoter activity of all six VNTRs of MNS16A in cell lines of colorectal, lung and prostate cancer using Luciferase reporter assay.
    [Show full text]
  • Genome-Wide Mapping and Characterization of Microsatellites In
    www.nature.com/scientificreports OPEN Genome-wide mapping and characterization of microsatellites in the swamp eel genome Received: 14 February 2017 Zhigang Li, Feng Chen, Chunhua Huang, Weixin Zheng, Chunlai Yu, Hanhua Cheng & Accepted: 26 April 2017 Rongjia Zhou Published: xx xx xxxx We described genome-wide screening and characterization of microsatellites in the swamp eel genome. A total of 99,293 microsatellite loci were identified in the genome with an overall density of 179 microsatellites per megabase of genomic sequences. The dinucleotide microsatellites were the most abundant type representing 71% of the total microsatellite loci and the AC-rich motifs were the most recurrent in all repeat types. Microsatellite frequency decreased as numbers of repeat units increased, which was more obvious in long than short microsatellite motifs. Most of microsatellites were located in non-coding regions, whereas only approximately 1% of the microsatellites were detected in coding regions. Trinucleotide repeats were most abundant microsatellites in the coding regions, which represented amino acid repeats in proteins. There was a chromosome-biased distribution of microsatellites in non-coding regions, with the highest density of 203.95/Mb on chromosome 8 and the least on chromosome 7 (164.06/Mb). The most abundant dinucleotides (AC)n was mainly located on chromosome 8. Notably, genomic mapping showed that there was a chromosome-biased association of genomic distributions between microsatellites and transposon elements. Thus, the novel dataset of microsatellites in swamp eel provides a valuable resource for further studies on QTL-based selection breeding, genetic resource conservation and evolutionary genetics. Swamp eel (Monopterus albus) taxonomically belongs to teleosts, the family Synbranchidae of the order Synbranchiformes (Neoteleostei, Teleostei, and Vertebrata).
    [Show full text]
  • A Monkey Alu Sequence Is Flanked by 13-Base-Pair Direct Repeats
    Proc. Natt Acad. Sci. USA Vol. 79, pp. 1497-1500, March 1982 Biochemistry A monkey Alu sequence is flanked by 13-base-pair direct repeats of an interrupted a-satellite DNA sequence (transposable element/repeated DNA/DNA sequence analysis) GIOVANNA GRIMALDI AND MAXINE F. SINGER Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Building 37, Room 4E-28, Bethesda, Maryland 20205 Contributed by Maxine F. Singer, December 11, 1981 ABSTRACT A member of the Alu family, the dominant family (16) supplied by Carl Schmid and Prescott Deininger; the se- of short interspersed repeated DNA sequences in primates, in- quence ofthis Alu is known (16). The conditions for hybridiza- terrupts a cloned repeat unit of African green monkey a-satellite tion were 0.05 M phosphate. buffer, pH 6.5/0.45 M NaCl/ DNA. TheAlu is immediately flanked by 13-base-pair duplications 0.045 M sodium citrate/0.2% bovine albumin/0.2% Ficoll/ of the known sequence ofthe satellite at the site ofinsertion. These 0.2% polyvinylpyrrolidone/0. 1% sodium lauryl sulfate contain- observations support the idea that Alu family members may be ing 500 jug ofdenatured sheared salmon sperm DNA and =100 moveable elements. ng ofdenatured 32P-labeled probe (5 x 106 cpm) in a total vol- ume of30 ml for 16 hr at 650C. Filters were washed at 550C for The Alu family of short interspersed DNA sequences is reit- three 1-hr periods in 0.03 M NaCV3 mM sodium citrate/0. 1% erated =3 x 105 times in the genomes of humans (1-3) and sodium lauryl sulfate.
    [Show full text]
  • Identification and Characterization of a Minisatellite Contained Within A
    Klein et al. Mobile DNA (2015) 6:18 DOI 10.1186/s13100-015-0049-1 RESEARCH Open Access Identification and characterization of a minisatellite contained within a novel miniature inverted-repeat transposable element (MITE) of Porphyromonas gingivalis Brian A. Klein1,2, Tsute Chen2, Jodie C. Scott2, Andrea L. Koenigsberg1, Margaret J. Duncan2 and Linden T. Hu1* Abstract Background: Repetitive regions of DNA and transposable elements have been found to constitute large percentages of eukaryotic and prokaryotic genomes. Such elements are known to be involved in transcriptional regulation, host-pathogen interactions and genome evolution. Results: We identified a minisatellite contained within a miniature inverted-repeat transposable element (MITE) in Porphyromonas gingivalis.TheP. gingivalis minisatellite and associated MITE, named ‘BrickBuilt’, comprises a tandemly repeating twenty-three nucleotide DNA sequence lacking spacer regions between repeats, and with flanking ‘leader’ and ‘tail’ subunits that include small inverted-repeat ends. Forms of the BrickBuilt MITE are found 19 times in thegenomeofP. gingivalis strain ATCC 33277, and also multiple times within the strains W83, TDC60, HG66 and JCVI SC001. BrickBuilt is always located intergenically ranging between 49 and 591 nucleotides from the nearest upstream and downstream coding sequences. Segments of BrickBuilt contain promoter elements with bidirectional transcription capabilities. Conclusions: We performed a bioinformatic analysis of BrickBuilt utilizing existing whole genome sequencing, microarray and RNAseq data, as well as performing in vitro promoter probe assays to determine potential roles, mechanisms and regulation of the expression of these elements and their affect on surrounding loci. The multiplicity, localization and limited host range nature of MITEs and MITE-like elements in P.
    [Show full text]