Editing Satellite DNA

{{Short description|Repetitive DNA with distinct base composition observed using isopycnic centrifugation.}}
'''Satellite DNA''' consists of very large arrays of [[tandem repeat|tandemly]] repeating, [[non-coding DNA]]. Satellite DNA is the main component of functional [[centromere]]s, and form the main structural constituent of [[heterochromatin]].<ref>{{cite journal |vauthors=Lohe AR, Hilliker AJ, Roberts PA |title=Mapping simple repeated DNA sequences in heterochromatin of Drosophila melanogaster |journal=Genetics |volume=134 |issue=4 |pages=1149–74 |date=August 1993 |doi=10.1093/genetics/134.4.1149 |pmid=8375654 |pmc=1205583 |url=https://academic.oup.com/genetics/article/134/4/1149/6011184}}</ref>

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(s) when genomic DNA is separated along a cesium chloride [[density gradient]] using [[buoyant density centrifugation#DNA separation|buoyant density centrifugation]].<ref name="Kit1">{{cite journal |issn=0022-2836 |volume=3 |issue=6 |pages=711–716 |last1=Kit |first1=S. |title=Equilibrium sedimentation in density gradients of DNA preparations from animal tissues |journal=J. Mol. Biol. |date=1961 |pmid=14456492 |doi=10.1016/S0022-2836(61)80075-2}}</ref>
Sequences with a greater ratio of A+T display a lower density while those with a greater ratio of G+C display a higher density than the bulk of genomic DNA. Some repetitive sequences are ~50% G+C/A+T and thus have buoyant densities the same as bulk genomic DNA. These satellites are called "cryptic" satellites because they form a band hidden within the main band of genomic DNA. "Isopycnic" is another term used for cryptic satellites.<ref>Skinner D.M., Beattie W.G., Blattner F.F., Stark B.P., Dahlberg J.E., Biochemistry. 1974; 13: 3930-3937</ref>

==Satellite DNA families in humans==
Satellite DNA, together with [[minisatellite]] and [[microsatellite]] DNA, constitute the [[tandem repeat]]s.<ref>{{MeSH name|Tandem+Repeat}}</ref> The size of satellite DNA arrays varies greatly between individuals.<ref name=":0">{{Cite journal |last1=Altemose |first1=Nicolas |last2=Logsdon |first2=Glennis A. |last3=Bzikadze |first3=Andrey V. |last4=Sidhwani |first4=Pragya |last5=Langley |first5=Sasha A. |last6=Caldas |first6=Gina V. |last7=Hoyt |first7=Savannah J. |last8=Uralsky |first8=Lev |last9=Ryabov |first9=Fedor D. |last10=Shew |first10=Colin J. |last11=Sauria |first11=Michael E. G. |last12=Borchers |first12=Matthew |last13=Gershman |first13=Ariel |last14=Mikheenko |first14=Alla |last15=Shepelev |first15=Valery A. |date=April 2022 |title=Complete genomic and epigenetic maps of human centromeres |journal=Science |language=en |volume=376 |issue=6588 |pages=eabl4178 |doi=10.1126/science.abl4178 |issn=0036-8075 |pmc=9233505 |pmid=35357911}}</ref>

The major satellite DNA families in humans are called:

{| class="wikitable"
|-
! Satellite family
! Size of repeat unit (bp)
! Location in human chromosomes
|-
| α (alphoid DNA)
| 170<ref name="TS87">{{cite journal
| volume=195
| issue=3
| pages=457–470
| last1=Tyler-Smith
| first1=Chris
| last2=Brown
| first2=William R. A.
| title=Structure of the major block of alphoid satellite DNA on the human Y chromosome| journal=Journal of Molecular Biology
| date=1987
| pmid=2821279
| doi=10.1016/0022-2836(87)90175-6}}</ref>
| All chromosomes
|-
| β
| 68
| Centromeres of chromosomes [[chromosome 1|1]], [[chromosome 9|9]], [[chromosome 13|13]], [[chromosome 14|14]], [[chromosome 15|15]], [[chromosome 21|21]], [[chromosome 22|22]], and [[Y chromosome|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 [[DNA motif|pattern]] can be between 1&nbsp;base pair (bp) long (a mononucleotide repeat) to several thousand base pairs long,<ref name="Fowler5"/> and the total size of a satellite DNA block can be several megabases without interruption. Long repeat units have been described containing domains of shorter repeated segments and mononucleotides (1-5&nbsp;bp), arranged in clusters of microsatellites, wherein differences among individual copies of the longer repeat units were clustered.<ref name="Fowler5"/> 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. 

Low-resolution sequencing-based studies have demonstrated variation in human population satellite array lengths as well as in the frequency of certain sequence and structural variations (11–13, 29). However, due to a lack of full centromere assemblies, base-level understanding of satellite array variation and evolution has remained weak.<ref name=":0" /> For example, [[minisatellite]] DNA is a short region (1-5&nbsp;kb) of repeating elements with length >9&nbsp;nucleotides. Whereas [[microsatellite]]s in DNA sequences are considered to have a length of 1-8&nbsp;nucleotides.<ref>{{cite journal | author1 = Richard GF | author2 = Kerrest A | author3 = Dujon B | author-link3 = Bernard Dujon| title = Comparative genomics and molecular dynamics of DNA repeats in eukaryotes | journal = Microbiology and Molecular Biology Reviews | volume = 72 | issue = 4 | pages = 686–727 | date = December 2008 | pmid = 19052325 | pmc = 2593564 | doi = 10.1128/MMBR.00011-08 }}</ref> The difference in how many of the repeats is present in the region (length of the region) is the basis for [[DNA profiling]].{{citation needed|date=January 2011}}

==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.<ref>{{cite journal |pmc=2997547 |pmid=20624737 |doi=10.1093/gbe/evq023 |volume=2 |title=DNA slippage occurs at microsatellite loci without minimal threshold length in humans: a comparative genomic approach |year=2010 |journal=Genome Biol Evol |pages=325–35 |last1=Leclercq |first1=S |last2=Rivals |first2=E |last3=Jarne |first3=P}}</ref>

==Structure==
Satellite DNA adopts higher-order three-dimensional structures in a naturally occurring complex satellite DNA from the land crab ''[[Gecarcinus lateralis]]'', whose genome contains 3% of a GC-rich satellite band consisting of a ~2100&nbsp;bp "repeat unit" sequence motif called RU.<ref name="Fowler8">{{cite journal
|volume=221
|issue=4613
|pages=862–865
|last1=Bonnewell
|first1=V.
|last2=Fowler
|first2=R. F.
|last3=Skinner
|first3=D. M.
|title=An inverted repeat borders a fivefold amplification in satellite DNA |journal=Science
|date=1983-08-26
|pmid=6879182
|doi=10.1126/science.6879182 |bibcode=1983Sci...221..862B
}}</ref><ref name="Fowler9">{{cite journal
|volume=47
|pages=1151–1157
|last1=Skinner
|first1=D. M.
|last2=Bonnewell
|first2=V.
|last3=Fowler
|first3=R. F.
|title=Sites of divergence in the sequence of a complex satellite DNA and several cloned variants
|journal=Cold Spring Harbor Symposia on Quantitative Biology
|date=1983
|pmid=6305575
|issue=2
|doi=10.1101/sqb.1983.047.01.130}}</ref> 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 over stretches greater than 550&nbsp;bp, interspersed with five "divergent domains" within each copy of RU.

Four divergent domains consisted of microsatellite repeats, biased in base composition, with purines on one strand and pyrimidines on the other. Some contained mononucleotide repeats of C:G base pairs approximately 20&nbsp;bp in length. These strand-biased microsatellite domains ranged in length from approximately 20&nbsp;bp to greater than 250&nbsp;bp. The most prevalent repeated sequences in the embedded microsatellite regions were CT:AG, CCT:AGG, CCCT:AGGG, and CGCAC:GTGCG<ref name="Fowler3"/><ref name="Fowler4"/><ref name="Fowler5"/> These repeating sequences were shown to adopt altered structures including [[triple-stranded DNA]], [[Z-DNA]], [[stem-loop]], and other conformations under [[DNA supercoil|superhelical stress]].<ref name="Fowler3">{{cite journal
|volume=261
|issue=19
|pages=8994–9001
|last1=Fowler
|first1=R. F.
|last2=Skinner
|first2=D. M.
|title=Eukaryotic DNA diverges at a long and complex pyrimidine:purine tract that can adopt altered conformations
|journal=The Journal of Biological Chemistry |date=1986-07-05
|doi=10.1016/S0021-9258(19)84479-4
|pmid=3013872|doi-access=free
}}</ref><ref name="Fowler4">{{cite journal
|volume=38
|issue=1–3
|pages=145–152
|last1=Stringfellow
|first1=L. A.
|last2=Fowler
|first2=R. F.
|last3=LaMarca
|first3=M. E.
|last4=Skinner
|first4=D. M.
|title=Demonstration of remarkable sequence divergence in variants of a complex satellite DNA by molecular cloning |journal=Gene
|date=1985
|pmid=3905513
|doi=10.1016/0378-1119(85)90213-6 |url=https://zenodo.org/record/1258505
}}</ref><ref name="Fowler5">{{cite journal
|volume=260
|issue=15
|pages=8964–8972
|last1=Fowler
|first1=R. F.
|last2=Bonnewell
|first2=V.
|last3=Spann
|first3=M. S.
|last4=Skinner
|first4=D. M.
|title=Sequences of three closely related variants of a complex satellite DNA diverge at specific domains
|journal=The Journal of Biological Chemistry
|date=1985-07-25
|doi=10.1016/S0021-9258(17)39443-7
|pmid=2991230|doi-access=free
}}</ref>

Between the strand-biased microsatellite repeats and C:G 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. These interruptions in compositional bias adopted highly distorted conformations as shown by their response to structrural nuclease enzymes including S1, P1, and mung bean nucleases.<ref name="Fowler3"/>

The most complex compositionally-biased microsatellite domain of RU included the sequence TTAA:TTAA as well as a mirror repeat. It produced the strongest signal in response to nucleases compared to all other altered structures in experimental observations. That particular strand-biased divergent domain was [[subcloning|subcloned]] and its altered helical structure was studied in greater detail.<ref name="Fowler3"/>

A fifth divergent domain in the RU sequence was characterized by variations of a symmetrical DNA sequence motif of alternating purines and pyrimidines shown to adopt a left-handed [[Z-DNA]] or [[stem-loop]] structure under superhelical stress. The conserved symmetrical Z-DNA was abbreviated Z<sub>4</sub>Z<sub>5</sub>NZ<sub>15</sub>NZ<sub>5</sub>Z<sub>4</sub>, where Z represents alternating purine/pyrimidine sequences. A [[stem-loop]] structure was centered in the Z<sub>15</sub> element at the highly conserved [[palindromic sequence]] CGCACGTGCG:CGCACGTGCG and was flanked by extended palindromic Z-DNA sequences over a 35&nbsp;bp region. Many RU variants showed deletions of at least 10 bp outside the Z<sub>4</sub>Z<sub>5</sub>NZ<sub>15</sub>NZ<sub>5</sub>Z<sub>4</sub> structural element, while others had additional Z-DNA sequences lengthening the alternating purine and pyrimidine domain to over 50&nbsp;bp.<ref name="Fowler6">{{cite journal |doi=10.1016/0378-1119(88)90088-1 |volume=71 |issue=1 |pages=165–176 |last1=Fowler |first1=R. F. |last2=Stringfellow |first2=L. A. |last3=Skinner |first3=D. M. |title=A domain that assumes a Z-conformation includes a specific deletion in some cloned variants of a complex satellite |journal=Gene |date=1988-11-15 |pmid=3215523 |url=https://zenodo.org/record/1258509}}</ref>

One extended RU sequence (EXT) was shown to have six tandem copies of a 142&nbsp;bp amplified (AMPL) sequence motif inserted into a region bordered by inverted repeats where most copies contained just one AMPL sequence element. There were no nuclease-sensitive altered structures or significant sequence divergence in the relatively conventional AMPL sequence. A truncated RU sequence (TRU), 327&nbsp;bp shorter than most clones, arose from a single base change leading to a second EcoRI restriction site in TRU.<ref name="Fowler8"/>

Another crab, the hermit crab ''[[Pagurus pollicaris]]'', was shown to have a family of AT-rich satellites with [[inverted repeat]] structures that comprised 30% of the entire genome. Another cryptic satellite from the same crab with the sequence CCTA:TAGG<ref>{{cite journal |last1=Skinner |first1=Dorothy M. |last2=Beattie |first2=Wanda G. |date=September 1974 |title=Characterization of a pair of isopycnic twin crustacean satellite deoxyribonucleic acids, one of which lacks one base in each strand |journal=Biochemistry |volume=13 |issue=19 |pages=3922–3929 |doi=10.1021/bi00716a017 |pmid=4412396 |issn=0006-2960}}</ref><ref>{{cite journal |last1=Chambers |first1=Carey A. |last2=Schell |first2=Maria P. |last3=Skinner |first3=Dorothy M. |title=The primary sequence of a crustacean satellite DNA containing a family of repeats |journal=Cell |date=January 1978 |volume=13 |issue=1 |pages=97–110 |doi=10.1016/0092-8674(78)90141-1 |pmid=620424|s2cid=42786386 }}</ref><ref>{{Cite journal |last=Skinner |first=D. M. |last2=Beattie |first2=W. G. |last3=Blattner |first3=F. R. |last4=Stark |first4=B. P. |last5=Dahlberg |first5=J. E. |date=1974-09-10 |title=The repeat sequence of a hermit crab satellite deoxyribonucleic acid is (-T-A-G-G-)n-(-A-T-C-C-)n |url=https://pubmed.ncbi.nlm.nih.gov/4607234/ |journal=Biochemistry |volume=13 |issue=19 |pages=3930–3937 |doi=10.1021/bi00716a018 |issn=0006-2960 |pmid=4607234}}</ref>
was found inserted into some of the palindromes.<ref name="Fowler19">{{cite journal
|volume=260
|issue=2
|pages=1296–1303
|last1=Fowler
|first1=R. F.
|last2=Skinner
|first2=D. M.
|title=Cryptic satellites rich in inverted repeats comprise 30% of the genome of a hermit crab |journal=The Journal of Biological Chemistry
|date=1985-01-25
|doi=10.1016/S0021-9258(20)71243-3
|pmid=2981841|doi-access=free
}}</ref>

==See also==
* [[Buoyant density centrifugation#DNA separation|Buoyant density centrifugation]]
* [[DNA profiling]]
* [[DNA supercoil]]
* [[Eukaryotic chromosome fine structure]]
* [[Gene expression]]
* [[Polymerase chain reaction]]
* [[Tengiz Beridze]], scientist who discovered satellite DNA in plants

==References==
{{Reflist}}

==Further reading==
* {{cite book |author=Beridze, Thengiz |title=Satellite DNA |publisher=Springer-Verlag |year=1986 |isbn=978-0-387-15876-1}}
* {{cite book |author=Hoy, Marjorie A. |title=Insect molecular genetics: an introduction to principles and applications |publisher=Academic Press |year=2003 |isbn=978-0-12-357031-4 |page=[https://archive.org/details/insectmolecularg0000hoym_f5j0/page/53 53] |url=https://archive.org/details/insectmolecularg0000hoym_f5j0 |url-access=registration}}

==External links==
* {{MeSH name|Satellite+DNA}}
* Search tools:
** [https://bioserf.org SERF] De Novo Genome Analysis and Tandem Repeats Finder
** [http://tandem.bu.edu/trf/trf.html TRF] Tandem Repeats Finder


{{Repeated sequence}}

[[Category:DNA]]
[[Category:Repetitive DNA sequences]]