Editing Non-coding DNA (section)

==Types of non-coding DNA sequences==
{{further|Conserved non-coding sequence}}

===Noncoding genes===
{{See also|Non-coding RNA}}

There are [[Gene|two types of genes]]: protein coding genes and [[Non-coding RNA|noncoding genes]].<ref>{{cite book | vauthors = Kampourakis K | date = 2017 | title = Making sense of genes | publisher = Cambridge University Press | place = Cambridge UK | isbn = 978-1-107-12813-2}}{{page needed|date=June 2022}}</ref> Noncoding genes are an important part of non-coding DNA and they include genes for [[transfer RNA]] and [[ribosomal RNA]]. These genes were discovered in the 1960s. [[Prokaryote|Prokaryotic]] genomes contain genes for a number of other noncoding RNAs but noncoding RNA genes are much more common in eukaryotes.

Typical classes of noncoding genes in eukaryotes include genes for [[small nuclear RNA]]s (snRNAs), [[small nucleolar RNA]]s (sno RNAs), [[microRNA]]s (miRNAs), [[Small interfering RNA|short interfering RNAs]] (siRNAs), [[Piwi-interacting RNA|PIWI-interacting RNAs]] (piRNAs), and [[Long non-coding RNA|long noncoding RNAs]] (lncRNAs). In addition, there are a number of unique RNA genes that produce [[Catalytic RNA|catalytic RNAs]].<ref>{{cite journal | vauthors=Cech TR, Steitz JA | title=The Noncoding RNA Revolution - Trashing Old Rules to Forge New Ones | journal=Cell|volume=157|pages=77–94|date=2014| issue=1 | doi=10.1016/j.cell.2014.03.008 | pmid=24679528 | s2cid=14852160 | doi-access=free }}</ref>

Noncoding genes account for only a few percent of prokaryotic genomes<ref>{{cite journal | vauthors = Rogozin IB, Makarova KS, Natale DA, Spiridonov AN, Tatusov RL, Wolf YI, Yin J, Koonin EV | display-authors = 6 | title = Congruent evolution of different classes of non-coding DNA in prokaryotic genomes | journal = Nucleic Acids Research | volume = 30 | issue = 19 | pages = 4264–4271 | date = October 2002 | pmid = 12364605 | pmc = 140549 | doi = 10.1093/nar/gkf549 }}</ref> but they can represent a vastly higher fraction in eukaryotic genomes.<ref>{{cite book |doi=10.1016/B978-0-12-800049-6.00171-2 |chapter=Adaptive Molecular Evolution: Detection Methods |title=Encyclopedia of Evolutionary Biology |year=2016 | vauthors = Bielawski JP, Jones C |pages=16–25 |isbn=978-0-12-800426-5 }}</ref> In humans, the noncoding genes take up at least 6% of the genome, largely because there are hundreds of copies of ribosomal RNA genes.{{citation needed|date=May 2022}} Protein-coding genes occupy about 38% of the genome; a fraction that is much higher than the coding region because genes contain large introns.{{citation needed|date=May 2022}}

The total number of noncoding genes in the human genome is controversial. Some scientists think that there are only about 5,000 noncoding genes while others believe that there may be more than 100,000 (see the article on [[Non-coding RNA]]). The difference is largely due to debate over the number of lncRNA genes.<ref>{{ cite journal | vauthors = Ponting CP, and Haerty W | date = 2022 | title = Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review | journal = Annual Review of Genomics and Human Genetics | volume = 23 | pages = 153–172 | doi = 10.1146/annurev-genom-112921-123710| pmid = 35395170 | s2cid = 248049706 | doi-access = free | hdl = 20.500.11820/ede40d70-b99c-42b0-a378-3b9b7b256a1b | hdl-access = free }}</ref>

===Promoters and regulatory elements===
{{Main|Promoter (genetics)}}

Promoters are DNA segments near the 5' end of the gene where transcription begins. They are the sites where [[RNA polymerase]] binds to initiate RNA synthesis. Every gene has a noncoding promoter.

[[Cis-regulatory element|Regulatory elements]] are sites that control the [[Transcription (genetics)|transcription]] of a nearby gene. They are almost always sequences where [[transcription factor]]s bind to DNA and these transcription factors can either activate transcription (activators) or repress transcription (repressors). Regulatory elements were discovered in the 1960s and their general characteristics were worked out in the 1970s by studying specific transcription factors in bacteria and [[bacteriophage]].{{citation needed|date=June 2022}}

Promoters and regulatory sequences represent an abundant class of noncoding DNA but they mostly consist of a collection of relatively short sequences so they do not take up a very large fraction of the genome. The exact amount of regulatory DNA in mammalian genome is unclear because it is difficult to distinguish between spurious transcription factor binding sites and those that are functional. The binding characteristics of typical [[DNA-binding protein]]s were characterized in the 1970s and the biochemical properties of transcription factors predict that in cells with large genomes, the majority of binding sites will not be biologically functional.{{citation needed|date=June 2022}}

Many regulatory sequences occur near promoters, usually upstream of the transcription start site of the gene. Some occur within a gene and a few are located downstream of the transcription termination site. In eukaryotes, there are some regulatory sequences that are located at a considerable distance from the promoter region. These distant regulatory sequences are often called [[Enhancer (genetics)|enhancers]] but there is no rigorous definition of enhancer that distinguishes it from other transcription factor binding sites.<ref>{{cite journal | vauthors = Compe E, Egly JM | title = The Long Road to Understanding RNAPII Transcription Initiation and Related Syndromes | journal = Annual Review of Biochemistry | volume = 90 | pages = 193–219 | date = 2021 | doi = 10.1146/annurev-biochem-090220-112253| pmid = 34153211 | s2cid = 235595550 }}</ref><ref>{{cite journal | vauthors = Visel A, Rubin EM, Pennacchio LA | title = Genomic views of distant-acting enhancers | journal = Nature | volume = 461 | issue = 7261 | pages = 199–205 | date = September 2009 | pmid = 19741700 | pmc = 2923221 | doi = 10.1038/nature08451 | author-link3 = Len A. Pennacchio | bibcode = 2009Natur.461..199V }}</ref>

===Introns===
{{Main|Intron}}

[[File:Pre-mRNA.svg|right|thumbnail|upright=1.35|Illustration of an unspliced pre-mRNA precursor, with five [[intron]]s and six [[exon]]s (top). After the introns have been removed via splicing, the mature mRNA sequence is ready for translation (bottom).]]

Introns are the parts of a gene that are transcribed into the [[precursor RNA]] sequence, but ultimately removed by [[RNA splicing]] during the processing to mature RNA. Introns are found in both types of genes: protein-coding genes and noncoding genes. They are present in prokaryotes but they are much more common in eukaryotic genomes.{{citation needed|date=June 2022}}

Group I and group II introns take up only a small percentage of the genome when they are present. Spliceosomal introns (see Figure) are only found in eukaryotes and they can represent a substantial proportion of the genome. In humans, for example, introns in protein-coding genes cover 37% of the genome. Combining that with about 1% coding sequences means that protein-coding genes occupy about 38% of the human genome. The calculations for noncoding genes are more complicated because there is considerable dispute over the total number of noncoding genes but taking only the well-defined examples means that noncoding genes occupy at least 6% of the genome.<ref>{{ cite journal | vauthors = Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S | date = 2012 | title = GENCODE: the reference human genome annotation for The ENCODE Project | journal = Genome Research | volume = 22 | issue = 9 | pages = 1760–1774 | doi = 10.1101/gr.135350.111| pmid = 22955987 | pmc = 3431492 }}</ref><ref name = Piovesan>{{ cite journal | vauthors = Piovesan A, Antonaros F, Vitale L, Strippoli P, Pelleri MC, Caracausi M | date = 2019 |  title = Human protein-coding genes and gene feature statistics in 2019 | journal = BMC Research Notes | volume = 12 | issue = 1 | pages = 315 | doi = 10.1186/s13104-019-4343-8| pmid = 31164174 | pmc = 6549324 | doi-access = free }}</ref>

===Untranslated regions===
{{Main|Untranslated region}}

The standard biochemistry and molecular biology textbooks describe non-coding [[Nucleotide|nucleotides]] in mRNA located between the 5' end of the gene and the translation initiation codon. These regions are called 5'-untranslated regions or 5'-UTRs. Similar regions called 3'-untranslated regions (3'-UTRs) are found at the end of the gene. The 5'-UTRs and 3'UTRs are very short in bacteria but they can be several hundred nucleotides in length in eukaryotes. They contain short elements that control the initiation of translation (5'-UTRs) and transcription termination (3'-UTRs) as well as regulatory elements that may control mRNA stability, processing, and targeting to different regions of the cell.<ref>{{cite book | vauthors = Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD | date = 1994 | title = Molecular Biology of the Cell, 3rd edition | publisher = Garland Publishing Inc. | place = London, UK}}{{page needed|date=June 2022}}</ref><ref>{{ cite book | vauthors = Lewin B | date = 2004 | title = Genes VIII | publisher = Pearson/Prentice Hall | place = Upper Saddle River, NJ, USA}}{{page needed|date=June 2022}}</ref><ref>{{ cite book | vauthors = Moran L, Horton HR, Scrimgeour KG, Perry MD | date = 2012 | title = Principles of Biochemistry Fifth Edition | publisher = Pearson | place = Upper Saddle River, NJ, USA}}{{page needed|date=June 2022}}</ref>

===Origins of replication===
{{Main|Origin of replication}}

DNA synthesis begins at specific sites called [[Origin of replication|origins of replication]]. These are regions of the genome where the DNA replication machinery is assembled and the DNA is unwound to begin DNA synthesis. In most cases, replication proceeds in both directions from the replication origin.

The main features of replication origins are sequences where specific initiation proteins are bound. A typical replication origin covers about 100-200 base pairs of DNA. Prokaryotes have one origin of replication per chromosome or plasmid but there are usually multiple origins in eukaryotic chromosomes. The human genome contains about 100,000 origins of replication representing about 0.3% of the genome.<ref>{{cite journal |vauthors=Leonard AC, Méchali M |title=DNA replication origins |journal=Cold Spring Harbor Perspectives in Biology |volume=5 |pages=a010116 |date=2013 |issue=10 |doi=10.1101/cshperspect.a010116|pmid=23838439 |pmc=3783049 }}</ref><ref>{{cite journal |vauthors=Urban JM, Foulk MS, Casella C, Gerbi SA |date=2015 |title=The hunt for origins of DNA replication in multicellular eukaryotes |journal=F1000Prime Reports |volume=7 |page=30 |doi=10.12703/P7-30|pmid=25926981 |pmc=4371235 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Prioleau M, MacAlpine DM |date=2016 |title=DNA replication origins—where do we begin? |journal=Genes & Development |volume=30 |issue=15 |pages=1683–1697 |doi=10.1101/gad.285114.116|pmid=27542827 |pmc=5002974 }}</ref>

===Centromeres===
{{Main|Centromere}}
[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[karyotype|karyogram]] of a human, showing an overview of the [[human genome]] on [[G banding]], wherein non-coding DNA is present at the centromeres (shown as narrow segment of each chromosome), and also occurs to a greater extent in darker ([[GC-content|GC poor]]) regions.<ref name=Romiguier2017>{{cite journal | vauthors = Romiguier J, Roux C | title = Analytical Biases Associated with GC-Content in Molecular Evolution | journal = Frontiers in Genetics | volume = 8 | issue =  | pages = 16 | year = 2017 | pmid = 28261263 | pmc = 5309256 | doi = 10.3389/fgene.2017.00016 | doi-access = free }} </ref>]]

Centromeres are the sites where spindle fibers attach to newly replicated chromosomes in order to segregate them into daughter cells when the cell divides. Each eukaryotic chromosome has a single functional centromere that is seen as a constricted region in a condensed metaphase chromosome. Centromeric DNA consists of a number of repetitive DNA sequences that often take up a significant fraction of the genome because each centromere can be millions of base pairs in length. In humans, for example, the sequences of all 24 centromeres have been determined<ref>{{ cite journal | vauthors = Altemose N, Logsdon GA, Bzikadze AV, Sidhwani P, Langley SA, Caldas GV, et al. | title = Complete genomic and epigenetic maps of human centromeres | journal = Science | volume = 376 | pages = 56 | date = 2021 | issue = 6588 | doi = 10.1126/science.abl4178| pmid = 35357911 | pmc = 9233505 | s2cid = 247853627 }}</ref> and they account for about 6% of the genome. However, it is unlikely that all of this noncoding DNA is essential since there is considerable variation in the total amount of centromeric DNA in different individuals.<ref>{{cite journal | vauthors = Miga KH | title = Centromeric satellite DNAs: hidden sequence variation in the human population | journal = Genes | volume = 10 | pages = 353 | date = 2019 | issue = 5 | doi = 10.3390/genes10050352| pmid = 31072070 | pmc = 6562703 | doi-access = free }}</ref> Centromeres are another example of functional noncoding DNA sequences that have been known for almost half a century and it is likely that they are more abundant than coding DNA.

===Telomeres===
{{Main|Telomere}}

Telomeres are regions of repetitive DNA at the end of a [[chromosome]], which provide protection from chromosomal deterioration during [[DNA replication]]. Recent studies have shown that telomeres function to aid in its own stability. [[Telomeric Repeat-Containing RNA (TERRA)|Telomeric repeat-containing RNA (TERRA)]] are transcripts derived from telomeres. TERRA has been shown to maintain telomerase activity and lengthen the ends of chromosomes.<ref>{{cite journal | vauthors = Cusanelli E, Chartrand P | title = Telomeric noncoding RNA: telomeric repeat-containing RNA in telomere biology | journal = Wiley Interdisciplinary Reviews. RNA | volume = 5 | issue = 3 | pages = 407–419 | date = May 2014 | pmid = 24523222 | doi = 10.1002/wrna.1220 | s2cid = 36918311 }}</ref>

===Scaffold attachment regions===
{{Main|Scaffold/matrix attachment region}}

Both prokaryotic and eukarotic genomes are organized into large loops of protein-bound DNA. In eukaryotes, the bases of the loops are called [[Scaffold/matrix attachment region|scaffold attachment regions]] (SARs) and they consist of stretches of DNA that bind an RNA/protein complex to stabilize the loop. There are about 100,000 loops in the human genome and each SAR consists of about 100 bp of DNA, so the total amount of DNA devoted to SARs accounts for about 0.3% of the human genome.<ref>{{cite journal | vauthors = Mistreli T | date = 2020 | title = The self-organizing genome: Principles of genome architecture and function | journal = Cell | volume = 183 | issue = 1 | pages = 28–45 | doi = 10.1016/j.cell.2020.09.014 | pmid = 32976797 | pmc = 7541718 }}</ref>

===Pseudogenes===
{{Main|Pseudogene}}

Pseudogenes are mostly former genes that have become non-functional due to mutation, but the term also refers to inactive DNA sequences that are derived from RNAs produced by functional genes ([[Pseudogene|processed pseudogenes]]). Pseudogenes are only a small fraction of noncoding DNA in prokaryotic genomes because they are eliminated by negative selection. In some eukaryotes, however, pseudogenes can accumulate because selection is not powerful enough to eliminate them (see [[Nearly neutral theory of molecular evolution]]).

The human genome contains about 15,000 pseudogenes derived from protein-coding genes and an unknown number derived from noncoding genes.<ref>{{ cite web | url = https://useast.ensembl.org/Homo_sapiens/Info/Annotation | title = Ensemble Human reference genome GRCh38.p13}}</ref> They may cover a substantial fraction of the genome (~5%) since many of them contain former intron sequences.

Pseudogenes are junk DNA by definition and they evolve at the neutral rate as expected for junk DNA.<ref>{{ cite journal | vauthors = Xu J, Zhang J | date = 2015 | title = Are human translated pseudogenes functional? | journal = Molecular Biology and Evolution | volume = 33 | issue = 3 | pages = 755–760 | doi = 10.1093/molbev/msv268 | pmid = 26589994 | pmc = 5009996 }}</ref> Some former pseudogenes have secondarily acquired a function and this leads some scientists to speculate that most pseudogenes are not junk because they have a yet-to-be-discovered function.<ref>{{ cite journal | vauthors = Wen YZ, Zheng LL, Qu LH, Ayala FJ, Lun ZR | date = 2012 | title = Pseudogenes are not pseudo any more. | journal = RNA Biology | volume = 9 | issue = 1 | pages = 27–32 |  doi = 10.4161/rna.9.1.18277 | pmid = 22258143 | s2cid = 13161678 | doi-access = free }}</ref>

===Repeat sequences, transposons and viral elements===
{{Main|Repeated sequence (DNA)}}

[[File:Bacterial mobile elements.svg|thumb|upright=1.35|[[Mobile genetic elements]] in the cell (left) and how they can be acquired (right)]]

[[Transposon]]s and [[retrotransposon]]s are [[mobile genetic elements]]. Retrotransposon [[Repeated sequence (DNA)|repeated sequences]], which include [[Retrotransposon#LINEs|long interspersed nuclear elements]] (LINEs) and [[Retrotransposon#SINEs|short interspersed nuclear elements]] (SINEs), account for a large proportion of the genomic sequences in many species. [[Alu sequence]]s, classified as a short interspersed nuclear element, are the most abundant mobile elements in the human genome. Some examples have been found of SINEs exerting transcriptional control of some protein-encoding genes.<ref>{{cite journal |vauthors=Ponicsan SL, Kugel JF, Goodrich JA |title=Genomic gems: SINE RNAs regulate mRNA production |journal=Current Opinion in Genetics & Development |volume=20 |issue=2 |pages=149–155 |date=April 2010 |pmid=20176473 |pmc=2859989 |doi=10.1016/j.gde.2010.01.004}}</ref><ref>{{cite journal |vauthors=Häsler J, Samuelsson T, Strub K |title=Useful 'junk': Alu RNAs in the human transcriptome |journal=Cellular and Molecular Life Sciences |volume=64 |issue=14 |pages=1793–1800 |date=July 2007 |pmid=17514354 |s2cid=5938630 |doi=10.1007/s00018-007-7084-0 |type=Submitted manuscript |url=https://archive-ouverte.unige.ch/unige:17489|pmc=11136058 }}</ref><ref>{{cite journal |vauthors=Walters RD, Kugel JF, Goodrich JA |title=InvAluable junk: the cellular impact and function of Alu and B2 RNAs |journal=IUBMB Life |volume=61 |issue=8 |pages=831–837 |date=August 2009 |pmid=19621349 |pmc=4049031 |doi=10.1002/iub.227}}</ref>

[[Endogenous retrovirus]] sequences are the product of [[reverse transcription]] of [[retrovirus]] genomes into the genomes of [[germ cell]]s. Mutation within these retro-transcribed sequences can inactivate the viral genome.<ref>{{cite journal | vauthors = Nelson PN, Hooley P, Roden D, Davari Ejtehadi H, Rylance P, Warren P, Martin J, Murray PG | display-authors = 6 | title = Human endogenous retroviruses: transposable elements with potential? | journal = Clinical and Experimental Immunology | volume = 138 | issue = 1 | pages = 1–9 | date = October 2004 | pmid = 15373898 | pmc = 1809191 | doi = 10.1111/j.1365-2249.2004.02592.x }}</ref>

Over 8% of the human genome is made up of (mostly decayed) endogenous retrovirus sequences, as part of the over 42% fraction that is recognizably derived of retrotransposons, while another 3% can be identified to be the remains of [[Transposon#DNA transposons|DNA transposon]]s. Much of the remaining half of the genome that is currently without an explained origin is expected to have found its origin in transposable elements that were active so long ago (> 200 million years) that random mutations have rendered them unrecognizable.<ref name=humangenome>{{cite journal | vauthors = Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J | display-authors = 6 | title = Initial sequencing and analysis of the human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 860–921 | date = February 2001 | pmid = 11237011 | doi = 10.1038/35057062 | doi-access = free | bibcode = 2001Natur.409..860L | hdl = 2027.42/62798 | hdl-access = free }}</ref> Genome size variation in at least two kinds of plants is mostly the result of retrotransposon sequences.<ref>{{cite journal | vauthors = Piegu B, Guyot R, Picault N, Roulin A, Sanyal A, Saniyal A, Kim H, Collura K, Brar DS, Jackson S, Wing RA, Panaud O | display-authors = 6 | title = Doubling genome size without polyploidization: dynamics of retrotransposition-driven genomic expansions in Oryza australiensis, a wild relative of rice | journal = Genome Research | volume = 16 | issue = 10 | pages = 1262–1269 | date = October 2006 | pmid = 16963705 | pmc = 1581435 | doi = 10.1101/gr.5290206 }}</ref><ref>{{cite journal | vauthors = Hawkins JS, Kim H, Nason JD, Wing RA, Wendel JF | title = Differential lineage-specific amplification of transposable elements is responsible for genome size variation in Gossypium | journal = Genome Research | volume = 16 | issue = 10 | pages = 1252–1261 | date = October 2006 | pmid = 16954538 | pmc = 1581434 | doi = 10.1101/gr.5282906 }}</ref>

===Highly repetitive DNA===

Highly repetitive DNA consists of short stretches of DNA that are repeated many times in [[Tandem repeat|tandem]] (one after the other). The repeat segments are usually between 2 bp and 10 bp but longer ones are known. Highly repetitive DNA is rare in prokaryotes but common in eukaryotes, especially those with large genomes. It is sometimes called [[satellite DNA]].

Most of the highly repetitive DNA is found in centromeres and telomeres (see above) and most of it is functional although some might be redundant. The other significant fraction resides in short tandem repeats (STRs; also called [[microsatellite]]s) consisting  of short stretches of a simple repeat such as ATC. There are about 350,000 STRs in the human genome and they are scattered throughout the genome with an average length of about 25 repeats.<ref>{{ cite journal | vauthors = Gymrek M, Willems T, Guilmatre A, Zeng H, Markus B, Georgiev S, Daly MJ, Price AL, Pritchard JK, Sharp AJ, Erlich Y | date = 2016 | title = Abundant contribution of short tandem repeats to gene expression variation in humans | journal = Nature Genetics | volume = 48 | issue = 1 | pages = 22–29 | doi = 10.1038/ng.3461| pmid = 26642241 | pmc = 4909355 }}</ref><ref>{{ cite journal | vauthors = Kronenberg ZN, Fiddes IT, Gordon D, Murali S, Cantsilieris S, Meyerson OS, Underwood JG, Nelson BJ, Chaisson MJ, Dougherty ML | date = 2018 | title=  High-resolution comparative analysis of great ape genomes | journal = Science | volume = 360 | issue = 6393 | pages = 1085 | doi = 10.1126/science.aar6343| pmid = 29880660 | pmc = 6178954 }}</ref>

Variations in the number of STR repeats can cause genetic diseases when they lie within a gene but most of these regions appear to be non-functional junk DNA where the number of repeats can vary considerably from individual to individual. This is why these length differences are used extensively in [[DNA profiling|DNA fingerprinting]].

===Junk DNA===
{{Main|Junk DNA}}
Junk DNA is DNA that has no biologically relevant function such as pseudogenes and fragments of once active transposons. Bacteria and viral genomes have very little junk DNA<ref>{{cite journal | vauthors = Gil R, and Latorre A | date = 2012 | title = Factors behind junk DNA in bacteria | journal = Genes | volume = 3 | issue = 4 | pages = 634–650 | doi = 10.3390/genes3040634 | pmid = 24705080 | pmc = 3899985 | doi-access = free }}</ref><ref>{{Cite journal |last1=Brandes |first1=Nadav |last2=Linial |first2=Michal |date=2016 |title=Gene overlapping and size constraints in the viral world |journal=Biology Direct |language=en |volume=11 |issue=1 |pages=26 |doi=10.1186/s13062-016-0128-3 |pmid=27209091 |pmc=4875738 |issn=1745-6150 |doi-access=free }}</ref> but some eukaryotic genomes may have a substantial amount of junk DNA.<ref name="PalazzoGregory2014">{{cite journal | vauthors = Palazzo AF, Gregory TR | title = The case for junk DNA | journal = PLOS Genetics | volume = 10 | issue = 5 | pages = e1004351 | date = May 2014 | pmid = 24809441 | pmc = 4014423 | doi = 10.1371/journal.pgen.1004351 | doi-access = free }}</ref> The exact amount of nonfunctional DNA in humans and other species with large genomes has not been determined and there is considerable controversy in the scientific literature.<ref>{{cite journal | last = Morange | first = Michel | date = 2014 | title = Genome as a Multipurpose Structure Built by Evolution | journal = Perspectives in Biology and Medicine | volume =  57 | issue = 1 | pages = 162–171 |  doi = 10.1353/pbm.2014.0008 | pmid = 25345709 | s2cid = 27613442 | url = https://hal.archives-ouvertes.fr/hal-01480552/file/ARTICLE%20ENCODE%20MM%2070114%20corrige%C2%A6%C3%BC.pdf }}</ref><ref>{{cite journal | vauthors = Haerty W, and Ponting CP | title = No Gene in the Genome Makes Sense Except in the Light of Evolution. | year = 2014 | journal = Annual Review of Genomics and Human Genetics | volume =25 | pages = 71–92 | doi = 10.1146/annurev-genom-090413-025621| pmid = 24773316 | doi-access = free }}</ref>

The nonfunctional DNA in bacterial genomes is mostly located in the intergenic fraction of non-coding DNA but in eukaryotic genomes it may also be found within [[introns]]. There are many examples of functional DNA elements in non-coding DNA, and it is erroneous to equate non-coding DNA with junk DNA.