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 the phenomenon that repetitions of a short DNA sequence tend to produce a different frequency of the bases 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.[3]

Types of satellite DNA

Satellite DNA, together with minisatellite and microsatellite DNA, constitute the tandem repeats.[4]

Some types of satellite DNA in humans are:

Type Size of repeat unit (bp) Location
α (alphoid DNA) 170 [5] 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.[6]

Pathology

Microsatellite 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.[7]

Structure

Satellite DNA adopts higher-order three-dimensional structures in eukaryotic organisms. This was demonstrated in the land crab Gecarcinus lateralis, whose genome contains 3% of a GC-rich sequence consisting of repeats of a ~2100 base pair (bp) sequence called RU. [8] [9] 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 five "divergent domains" within each copy of RU.

Four divergent domains consisted of microsatellite repeats biased in composition with purines on one strand and pyrimidines on the other, including mononucleotide repeats of C:G base pairs approximately 20 bp in length. The most prevalent repeated sequences in the embedded microsatellite regions were CCT:AGG, CTT:AAG, CTTT:AAAG, and CCCT:AGGG.[10][11][12] These strand biased pyrimidine:purine repeating sequences were shown to adopt triple-stranded structures under superhelical stress or at slightly acidic pH.[10] [10] [11] [12]

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 that particular strand-biased divergent domain was subcloned and its altered helical structure was studied in greater detail.[10]

A fifth divergent domain in 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. 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 divergent domains 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. [13]

In all RU variants examined, tandem repeats of the CGCAC:GTGCG sequence motif were also found adjacent to a C:G mononucleotide repeat within one of the repetitive pyrimidine:purine divergent domains.

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.[8][9][10][11][12][13]

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.[8]

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.[14]

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. ↑ Kit, S. (1961). "Equilibrium sedimentation in density gradients of DNA preparations from animal tissues". J. Mol. Biol. 3 (6): 711–716. doi:10.1016/S0022-2836(61)80075-2. ISSN 0022-2836. PMID 14456492.
  4. ↑ Tandem+Repeat at the US National Library of Medicine Medical Subject Headings (MeSH)
  5. ↑ Tyler-Smith, Chris; Brown, William R. A. (1987). "Structure of the major block of alphoid satellite DNA on the human Y chromosome". Journal of Molecular Biology. 195 (3): 457–470. doi:10.1016/0022-2836(87)90175-6. PMID 2821279.
  6. ↑ Leclercq, S; Rivals, E; Jarne, P (2010). "DNA slippage occurs at microsatellite loci without minimal threshold length in humans: a comparative genomic approach". Genome Biol Evol. 2: 325–35. doi:10.1093/gbe/evq023. PMC 2997547. PMID 20624737.
  7. ↑ Usdin, K (2008). "The biological effects of simple tandem repeats: lessons from the repeat expansion diseases". Genome Res. 18 (7): 1011–9. doi:10.1101/gr.070409.107. PMC 3960014. PMID 18593815.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. ↑ 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

  • Beridze, Thengiz (1986). Satellite DNA. Springer-Verlag. ISBN 978-0-387-15876-1.
  • Hoy, Marjorie A. (2003). Insect molecular genetics: an introduction to principles and applications. Academic Press. p. 53. ISBN 978-0-12-357031-4.
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