Repeated sequence (DNA)
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Repeated sequences (also known as repetitive elements, 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 reassociation 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.
Repetitive elements found in genomes fall into different classes, depending on their mode of multiplication and/or structure. 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. Originally discovered by Barbara McClintock, 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. 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.
Tandem repeats in human disease
Tandem repeat sequences, particularly trinuceotide 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. Trinucleotide repeat expansions may occur through strand slippage during DNA replication or during DNA repair synthesis.
There are 3 major categories of repeated sequence or repeats:
- Terminal repeats
- Tandem repeats: 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)
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.
Note: The following are covered in detail in "Computing for Comparative Microbial Genomics".
- 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
- de Koning, AP Jason, et al. "Repetitive elements may comprise over two-thirds of the human genome." PLoS Genet 7.12 (2011): e1002384.
- Ohno, Susumu. "So much “junk” DNA in our genome." Brookhaven Symp Biol. Vol. 23. 1972.
- Orgel, Leslie E., F. H. C. Crick, and C. Sapienza. "Selfish dna." (1980): 645-646.
- McClintock B.Controlling element and the gene. Cold Spring Harb. Symp. Quant. Biol. 1956;21:197-216.
- Shapiro J.A., von Sternberg R.Why repetitive DNA is essential to genome function. Biol. Rev. 2005;80:227-250.
- The 3D folding of metazoan genomes correlates with the association of similar repetitive elementsA Cournac, R Koszul, J Mozziconacci - Nucleic Acids Research, 2016
- 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 . PMID 25608779.
- 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.