Satellite DNA

Satellite DNA consists of very large arrays of tandemly repeating, non-coding DNA. Satellite DNA is the main component of functional centromeres, and form the main structural constituent of heterochromatin.[1][2]

The name "satellite DNA" refers to how repetitions of a short DNA sequence tend to produce a different frequency of the nucleotides adenine, cytosine, guanine and thymine, and thus have a different density from bulk DNA - such that they form a second or 'satellite' band when genomic DNA is separated on a density gradient.

Types of satellite DNA

Satellite DNA, together with minisatellite and microsatellite DNA, constitute the tandem repeats.[3]

Some types of satellite DNA in humans are:

Type Size of repeat unit (bp) Location
α (alphoid DNA) 171 All chromosomes
β 68 Centromeres of chromosomes 1, 9, 13, 14, 15, 21, 22 and Y
Satellite 1 25-48 Centromeres and other regions in heterochromatin of most chromosomes
Satellite 2 5 Most chromosomes
Satellite 3 5 Most chromosomes

Length

A repeated pattern can be between 1 base pair long (a mononucleotide repeat) to several thousand base pairs long, and the total size of a satellite DNA block can be several megabases without interruption. Most satellite DNA is localized to the telomeric or the centromeric region of the chromosome. The nucleotide sequence of the repeats is fairly well conserved across species. However, variation in the length of the repeat is common. For example, minisatellite DNA is a short region (1-5kb) of 20-50 repeats. The difference in how many of the repeats is present in the region (length of the region) is the basis for DNA fingerprinting.

Origin

Microsatellites are thought to have originated by polymerase slippage during DNA replication. This comes from the observation that microsatellite alleles usually are length polymorphic; specifically, the length differences observed between microsatellite alleles are generally multiples of the repeat unit length.

Pathology

Microsatellites expansion (trinucleotide repeat expansion) is often found in transcription units. Often the base pair repetition will disrupt proper protein synthesis, leading to diseases such as myotonic dystrophy.

Structure

Satellite DNA adopts higher-order three-dimensional structures in eukaryotic organisms. This was demonstrated in the land crab Gecarcinus lateralis, whose DNA contains 3% of a GC-rich sequence consisting of repeats of a ~2100 base pair (bp) sequence called RU. [4] [5] The RU was arranged in long tandem arrays with approximately 16,000 copies per genome. Several RU sequences were cloned and sequenced to reveal conserved regions of conventional DNA sequences interspersed with four domains of microsatellite repeats biased in composition with purines on one strand and pyrimidines on the other, including mononucleotide repeats of G and C base pairs 20-25 bp in length. The most prevalent repeated sequences in the embedded microsatellite regions were CCT:AGG and CCCT:AGGG.[6][7][8] The strand biased pyrimidine:purine repeating sequences were shown to adopt triple-stranded structures under superhelical stress or at slightly acidic pH.[6] [6] [7] [8]

Between the strand-biased microsatellite repeats and G:C mononucleotide repeats, all sequence variations retained one or two base pairs with A (purine) interrupting the pyrimidine-rich strand and T (pyrimidine) interrupting the purine-rich strand. This sequence feature adopted a highly distorted conformation as shown by its response to nuclease enzymes. The sequence TTAA was found in one variant of RU, and the strand-biased domain was subcloned and studied in greater detail.[6]

A fifth region of the RU sequence was characterized by variations of a symmetrical DNA sequence of alternating purines and pyrimidines shown to adopt a left-handed Z-DNA helical structure in equilibrium with a stem-loop structure under superhelical stress. The sequence consisted of CGCAC:GTGCG and variations that retained the alternating purine and pyrimidine motif. A fragment containing the domain was excised and subcloned in order to examine structural properties of the alternating purine and pyrimidine motif independently of the four compositionally-biased repetitive sequences within RU. The palindromic sequence CGCACGTGCG:CGCACGTGCG, flanked by extended palindromic Z-DNA sequences over a 35 bp domain, adopted a Z-DNA structure with a symmetrical arrangement in equilibrium with a stem-loop structure centered on the palindrome containing the CGCAC:GTGCG motif. The CGCAC:GTGCG sequence was also found in tandem repeats with at least five copies immediately adjacent to one of the pyrimidine:purine biased divergent domains. [9]

Conserved sequences showed virtually no differences among cloned RU sequences. Variations among cloned RU sequences were characterized by the number of microsatellite repeats, and also by the lengths of C and G stretches where triple stranded structures formed. Other regions of variability among cloned RU sequences were found adjacent to alternating purine and pyrimidine sequences with Z-DNA/stem-loop structures.[4][5][6][7][8][9]

One RU sequence was shown to have multiple copies of an Alu sequence element inserted into a region bordered by inverted repeats where most copies contained just one Alu sequence.[4]

Another crab, the hermit crab Pagurus policarus, was shown to have a family of AT-rich satellites with inverted repeat structures that comprised 30% of the entire genome.[10]

See also

References

  1. ↑ Knight, Julian C. (2009). Human Genetic Diversity: Functional Consequences for Health and Disease. Oxford University Press. p. 167. ISBN 978-0-19-922769-3.
  2. ↑ "satellite DNA" at Dorland's Medical Dictionary
  3. ↑ Tandem Repeat at the US National Library of Medicine Medical Subject Headings (MeSH)
  4. 1 2 3 Bonnewell, V.; Fowler, R. F.; Skinner, D. M. (1983-08-26). "An inverted repeat borders a fivefold amplification in satellite DNA". Science. 221 (4613): 862–865. doi:10.1126/science.6879182. ISSN 0036-8075. PMID 6879182.
  5. 1 2 Skinner, D. M.; Bonnewell, V.; Fowler, R. F. (1983). "Sites of divergence in the sequence of a complex satellite DNA and several cloned variants". Cold Spring Harbor Symposia on Quantitative Biology. 47 (2): 1151–1157. doi:10.1101/sqb.1983.047.01.130. ISSN 0091-7451. PMID 6305575.
  6. 1 2 3 4 5 Fowler, R. F.; Skinner, D. M. (1986-07-05). "Eukaryotic DNA diverges at a long and complex pyrimidine:purine tract that can adopt altered conformations". The Journal of Biological Chemistry. 261 (19): 8994–9001. ISSN 0021-9258. PMID 3013872.
  7. 1 2 3 Stringfellow, L. A.; Fowler, R. F.; LaMarca, M. E.; Skinner, D. M. (1985). "Demonstration of remarkable sequence divergence in variants of a complex satellite DNA by molecular cloning". Gene. 38 (1-3): 145–152. doi:10.1016/0378-1119(85)90213-6. ISSN 0378-1119. PMID 3905513.
  8. 1 2 3 Fowler, R. F.; Bonnewell, V.; Spann, M. S.; Skinner, D. M. (1985-07-25). "Sequences of three closely related variants of a complex satellite DNA diverge at specific domains". The Journal of Biological Chemistry. 260 (15): 8964–8972. ISSN 0021-9258. PMID 2991230.
  9. 1 2 Fowler, R. F.; Stringfellow, L. A.; Skinner, D. M. (1988-11-15). "A domain that assumes a Z-conformation includes a specific deletion in some cloned variants of a complex satellite". Gene. 71 (1): 165–176. doi:10.1016/0378-1119(88)90088-1. ISSN 0378-1119. PMID 3215523.
  10. ↑ Fowler, R. F.; Skinner, D. M. (1985-01-25). "Cryptic satellites rich in inverted repeats comprise 30% of the genome of a hermit crab". The Journal of Biological Chemistry. 260 (2): 1296–1303. ISSN 0021-9258. PMID 2981841.

Further reading

External links

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