Repeated sequence (DNA)

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Repeated sequences (also known as repetitive elements, repeating units or repeats) are patterns of nucleic acids (DNA or RNA) that occur in multiple copies throughout the genome. Repetitive DNA was first detected because of its rapid re-association kinetics. In many organisms, a significant fraction of the genomic DNA is highly repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans.[1]

Repetitive elements found in genomes fall into different classes, depending on their structure and/or the mode of multiplication. The disposition of repetitive elements consists either in arrays of tandemly repeated sequences, or in repeats dispersed throughout the genome (see below).


Debates regarding the potential functions of these elements have been long standing. Controversial references to ‘junk’ or ‘selfish’ DNA were put forward early on, implying that repetitive DNA segments are remainders from past evolution or autonomous self-replicating sequences hacking the cell machinery to proliferate.[2][3] Originally discovered by Barbara McClintock,[4] dispersed repeats have been increasingly recognized as a potential source of genetic variation and regulation. Together with these regulatory roles, a structural role of repeated DNA in shaping the 3D folding of genomes has also been proposed.[5] This hypothesis is only supported by a limited set of experimental evidence. For instance in human, mouse and fly, several classes of repetitive elements present a high tendency for co-localization within the nuclear space, suggesting that DNA repeats positions can be used by the cell as a genome folding map.[6]

Tandem repeats in human disease[edit]

Tandem repeat sequences, particularly trinucleotide repeats, underlie several human disease conditions. Trinucleotide repeats may expand in the germline over successive generations leading to increasingly severe manifestations of the disease. The disease conditions in which expansion occurs include Huntington’s disease, fragile X syndrome, several spinocerebellar ataxias, myotonic dystrophy and Friedrich ataxia.[7] Trinucleotide repeat expansions may occur through strand slippage during DNA replication or during DNA repair synthesis.[7]

Hexanucleotide GGGGCC repeat sequences in the C9orf72 gene are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia.[8] CAG trinucleotide repeat sequences underlie several spinocerebellar ataxias (SCAs-SCA1; SCA2; SCA3; SCA6; SCA7; SCA12; SCA17).[8] Huntington’s disease results from an unstable expansion of repeated CAG sequences in exon 1 of the huntingtin gene (HTT). HTT encodes a scaffold protein that directly participates in repair of oxidative DNA damage.[9] It has been noted that genes containing pathogenic CAG repeats often encode proteins that themselves have a role in the DNA damage response and that repeat expansions may impair specific DNA repair pathways.[10] Faulty repair of DNA damages in repeat sequences may cause further expansion of these sequences, thus setting up a vicious cycle of pathology.[10]


Main types[edit]

Major categories of repeated sequence or repeats: Tandem repeats: are copies which lie adjacent to each other, either directly or inverted.Satellite DNA - typically found in centromeres and heterochromatin. Minisatellite - repeat units from about 10 to 60 base pairs, found in many places in the genome, including the centromeres. Microsatellite - repeat units of less than 10 base pairs; this includes telomeres, which typically have 6 to 8 base pair repeat units.Interspersed repeats (aka. interspersed nuclear elements). Transposable elements. DNA transposons.retrotransposons.LTR-retrotransposons (HERVs).non LTR-retrotransposons.SINEs (Short Interspersed Nuclear Elements).LINEs (Long Interspersed Nuclear Elements).SVAs

In primates, the majority of LINEs are LINE-1 and the majority of SINEs are Alu's. SVAs are hominoid specific.

In prokaryotes, CRISPR are arrays of alternating repeats and spacers.

Other types[edit]

Note: The following are covered in detail in "Computing for Comparative Microbial Genomics".[11]

  • Direct repeats
    • Global direct repeat
    • Local direct simple repeats
    • Local direct repeats
    • Local direct repeats with spacer
  • Inverted repeats
    • Global inverted repeat
    • Local inverted repeat
    • Inverted repeat with spacer
    • Palindromic repeat
  • Mirror and everted repeats

See also[edit]


  1. ^ de Koning, AP Jason, et al. "Repetitive elements may comprise over two-thirds of the human genome." PLoS Genet 7.12 (2011): e1002384.
  2. ^ Ohno, Susumu. "So much “junk” DNA in our genome." Brookhaven Symp Biol. Vol. 23. 1972.
  3. ^ Orgel, Leslie E., F. H. C. Crick, and C. Sapienza. "Selfish dna." (1980): 645-646.
  4. ^ McClintock B.Controlling element and the gene. Cold Spring Harb. Symp. Quant. Biol. 1956;21:197-216.
  5. ^ Shapiro J.A., von Sternberg R.Why repetitive DNA is essential to genome function. Biol. Rev. 2005;80:227-250.
  6. ^ The 3D folding of metazoan genomes correlates with the association of similar repetitive elementsA Cournac, R Koszul, J Mozziconacci - Nucleic Acids Research, 2016
  7. ^ a b Usdin K, House NC, Freudenreich CH (2015). "Repeat instability during DNA repair: Insights from model systems". Crit. Rev. Biochem. Mol. Biol. 50 (2): 142–67. doi:10.3109/10409238.2014.999192. PMC 4454471. PMID 25608779.
  8. ^ a b Abugable AA, Morris JLM, Palminha NM, Zaksauskaite R, Ray S, El-Khamisy SF. DNA repair and neurological disease: From molecular understanding to the development of diagnostics and model organisms. DNA Repair (Amst). 2019 Sep;81:102669. doi: 10.1016/j.dnarep.2019.102669. Epub 2019 Jul 8. Review. PMID:31331820
  9. ^ Maiuri T, Mocle AJ, Hung CL, Xia J, van Roon-Mom WM, Truant R. Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex. Hum Mol Genet. 2017 Jan 15;26(2):395-406. doi: 10.1093/hmg/ddw395. PMID: 28017939
  10. ^ a b Massey TH, Jones L. The central role of DNA damage and repair in CAG repeat diseases. Dis Model Mech. 2018 Jan 30;11(1). pii: dmm031930. doi: 10.1242/dmm.031930. Review. PMID: 29419417
  11. ^ Ussery, David W.; Wassenaar, Trudy; Borini, Stefano (2008-12-22). "Word Frequencies, Repeats, and Repeat-related Structures in Bacterial Genomes". Computing for Comparative Microbial Genomics: Bioinformatics for Microbiologists. Computational Biology. 8 (1 ed.). Springer. pp. 133–144. ISBN 978-1-84800-254-8.

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