Editing Internal transcribed spacer

{{Short description|Intergenic DNA sequence separating ribosomal RNA genes}}
'''Internal transcribed spacer''' ('''ITS''') is the [[spacer DNA]] situated between the small-subunit [[ribosomal RNA]] (rRNA) and large-subunit [[Ribosomal DNA|rRNA genes]] in the [[chromosome]] or the corresponding [[Transcription (genetics)|transcribed]] region in the [[polycistronic]] rRNA precursor transcript.

== Across life domains ==
In [[bacteria]] and [[archaea]], there is a single ITS, located between the [[16S ribosomal RNA|16S]] and [[23S ribosomal RNA|23S]] rRNA genes. Conversely, there are two ITSs in [[eukaryotes]]: '''ITS1''' is located between [[18S ribosomal RNA|18S]] and [[5.8S ribosomal RNA|5.8S]] rRNA genes, while '''ITS2''' is between 5.8S and [[28S ribosomal RNA|28S]] (in [[opisthokont]]s, or 25S in plants) rRNA genes. ITS1 corresponds to the ITS in bacteria and archaea, while ITS2 originated as an insertion that interrupted the ancestral 23S rRNA gene.<ref>{{Cite journal | doi = 10.1038/35080045| pmid = 11433365| title = The function and synthesis of ribosomes| journal = Nature Reviews Molecular Cell Biology| volume = 2| issue = 7| pages = 514–520| year = 2001| last1 = Lafontaine | first1 = D. L. J. | last2 = Tollervey | first2 = D. | hdl = 1842/729| s2cid = 2637106| hdl-access = free}}</ref><ref name="Rogers2011">{{cite book|author=Scott Orland Rogers|title=Integrated Molecular Evolution|url=https://books.google.com/books?id=xywnbQMKzXwC&pg=PA66|access-date=9 March 2015|date=27 July 2011|publisher=CRC Press|isbn=978-1-4398-1995-1|pages=65–66}}</ref>

== Organization ==
[[File:Eucaryot rdna.png|thumb|right|Organization of the eukaryotic nuclear ribosomal DNA tandem repeats]]

In [[bacteria]] and [[archaea]], the ITS occurs in one to several copies, as do the flanking 16S and [[23S ribosomal RNA|23S]] genes. When there are multiple copies, these do not occur adjacent to one another. Rather, they occur in discrete locations in the circular chromosome. It is not uncommon in bacteria to carry [[tRNA]] genes in the ITS.<ref>{{cite journal |last1=Takada |first1=Hiraku |last2=Shimada |first2=Tomohiro |last3=Dey |first3=Debashish |last4=Quyyum |first4=M. Zuhaib |last5=Nakano |first5=Masahiro |last6=Ishiguro |first6=Akira |last7=Yoshida |first7=Hideji |last8=Yamamoto |first8=Kaneyoshi |last9=Sen |first9=Ranjan |last10=Ishihama |first10=Akira |title=Differential Regulation of rRNA and tRNA Transcription from the rRNA-tRNA Composite Operon in Escherichia coli |journal=PLOS ONE |date=22 December 2016 |volume=11 |issue=12 |pages=e0163057 |doi=10.1371/journal.pone.0163057|pmid=28005933 |pmc=5179076 |bibcode=2016PLoSO..1163057T |doi-access=free }}</ref><ref>{{cite journal |last1=Stewart |first1=Frank J. |last2=Cavanaugh |first2=Colleen M. |title=Intragenomic Variation and Evolution of the Internal Transcribed Spacer of the rRNA Operon in Bacteria |journal=Journal of Molecular Evolution |date=July 2007 |volume=65 |issue=1 |pages=44–67 |doi=10.1007/s00239-006-0235-3|pmid=17568983 |bibcode=2007JMolE..65...44S |s2cid=13536182 |citeseerx=10.1.1.456.2659 }}</ref>

In eukaryotes, genes encoding ribosomal RNA and spacers occur in [[tandem repeat]]s that are thousands of copies long, each separated by regions of non-transcribed DNA termed ''[[intergenic spacer]]'' (IGS) or ''non-transcribed spacer'' (NTS).

Each eukaryotic ribosomal cluster contains the 5' [[external transcribed spacer]] (5' ETS), the [[18S rRNA]] gene, the ITS1, the [[5.8S rRNA]] gene, the ITS2, the [[28S rRNA|26S or 28S rRNA]] gene, and finally the 3' ETS.<ref name="Bena1998">{{Cite journal|last1=Bena|first1=Gilles|last2=Jubier|first2=Marie-France|last3=Olivieri|first3=Isabelle|last4=Lejeune|first4=Bernard|year=1998|title=Ribosomal External and Internal Transcribed Spacers: Combined Use in the Phylogenetic Analysis of ''Medicago'' (Leguminosae)|journal=Journal of Molecular Evolution|volume=46|issue=3|pages=299–306|doi=10.1007/PL00006306|pmid=9502673|issn=0022-2844|bibcode=1998JMolE..46..299B|s2cid=38838013}}</ref>

During rRNA maturation, ETS and ITS pieces are excised. As non-functional by-products of this maturation, they are rapidly degraded.<ref>{{Cite journal|last1=Michot|first1=Bernard|last2=Bachellerie|first2=Jean-Pierre|last3=Raynal|first3=Francoise|date=1983-05-25|title=Structure of mouse rRNA precursors. Complete sequence and potential folding of the spacer regions between 18S and 28S rRNA|journal=Nucleic Acids Research|volume=11|issue=10|pages=3375–3391|doi=10.1093/nar/11.10.3375|pmid=6304630|pmc=325970|issn=0305-1048}}</ref>

== Use in phylogenetic inference ==
Sequence comparison of the eukaryotic ITS regions is widely used in [[Taxonomy (biology)|taxonomy]] and [[molecular phylogeny]] because of several favorable properties:<ref>{{Cite journal|last1=Baldwin|first1=Bruce G.|last2=Sanderson|first2=Michael J.|last3=Porter|first3=J. Mark|last4=Wojciechowski|first4=Martin F.|last5=Campbell|first5=Christopher S.|last6=Donoghue|first6=Michael J.|date=1995-01-01|title=The ITS Region of Nuclear Ribosomal DNA: A Valuable Source of Evidence on Angiosperm Phylogeny|jstor=2399880|journal=Annals of the Missouri Botanical Garden|volume=82|issue=2|pages=247–277|doi=10.2307/2399880}}</ref>
* It is routinely amplified thanks to its small size associated to the availability of highly conserved flanking sequences.
* It is easy to detect even from small quantities of DNA due to the high copy number of the rRNA clusters.
* It undergoes rapid [[concerted evolution]] via unequal crossing-over and gene conversion. This promotes intra-genomic homogeneity of the repeat units, although high-throughput sequencing showed the occurrence of frequent variations within plant species.<ref>{{Cite journal|last1=Song|first1=Jingyuan|last2=Shi|first2=Linchun|last3=Li|first3=Dezhu|last4=Sun|first4=Yongzhen|last5=Niu|first5=Yunyun|last6=Chen|first6=Zhiduan|last7=Luo|first7=Hongmei|last8=Pang|first8=Xiaohui|last9=Sun|first9=Zhiying|date=2012-08-30|title=Extensive Pyrosequencing Reveals Frequent Intra-Genomic Variations of Internal Transcribed Spacer Regions of Nuclear Ribosomal DNA|journal=PLOS ONE|volume=7|issue=8|pages=e43971|doi=10.1371/journal.pone.0043971|issn=1932-6203|pmc=3431384|pmid=22952830|bibcode=2012PLoSO...743971S|doi-access=free}}</ref>
* It has a high degree of variation even between closely related species. This can be explained by the relatively low evolutionary pressure acting on such non-coding spacer sequences.

For example, ITS markers have proven especially useful for elucidating phylogenetic relationships among the following taxa.

{| class="wikitable sortable"
|-
! Taxonomic group
! Taxonomic level
! Year
! Authors with references
|-
| [[Asteraceae]]: [[Compositae]]
| Species (congeneric)
| 1992
| Baldwin et al.<ref>{{cite journal | author=Baldwin, B.G.| title=Phylogenetic utility of the internal transcribed spacers of nuclear ribosomal DNA in plants: An example from the Compositae| journal=Molecular Phylogenetics and Evolution| year=1992 |pages=3–16|volume=1 | doi=10.1016/1055-7903(92)90030-K | pmid=1342921 | issue=1}}</ref>
|-
|[[Viscaceae]]: ''[[Arceuthobium]]''
|Species (congeneric)
|1994
|Nickrent et al.<ref>{{Cite journal|last1=Nickrent|first1=Daniel L.|last2=Schuette|first2=Kevin P.|last3=Starr|first3=Ellen M.|date=1994-01-01|title=A Molecular Phylogeny of ''Arceuthobium'' (Viscaceae) Based on Nuclear Ribosomal DNA Internal Transcribed Spacer Sequences|jstor=2445477|journal=American Journal of Botany|volume=81|issue=9|pages=1149–1160|doi=10.2307/2445477}}</ref>
|-
|[[Poaceae]]: [[Zea (plant)|''Zea'']]
|Species (congeneric)
|1996
|Buckler & Holtsford<ref>{{Cite journal|last1=Buckler|first1=E. S.|last2=Holtsford|first2=T. P.|date=1996-04-01|title=''Zea'' systematics: ribosomal ITS evidence.|journal=Molecular Biology and Evolution|volume=13|issue=4|pages=612–622|issn=0737-4038|pmid=8882504|doi=10.1093/oxfordjournals.molbev.a025621|doi-access=}}</ref>
|-
| [[Leguminosae]]: ''[[Medicago]]''
| Species (congeneric)
| 1998
| Bena et al.<ref name="Bena1998"/>
|-
|[[Orchidaceae]]: [[Diseae]]
|Genera (within tribes)
|1999
|Douzery et al.<ref>{{Cite journal|last1=Douzery|first1=Emmanuel J. P.|last2=Pridgeon|first2=Alec M.|last3=Kores|first3=Paul|last4=Linder|first4=H. P.|last5=Kurzweil|first5=Hubert|last6=Chase|first6=Mark W.|date=1999-06-01|title=Molecular phylogenetics of Diseae (Orchidaceae): a contribution from nuclear ribosomal ITS sequences|journal=American Journal of Botany|volume=86|issue=6|pages=887–899|issn=0002-9122|pmid=10371730|doi=10.2307/2656709|jstor=2656709}} {{subscription required}}</ref>
|-
|[[Odonata]]: [[Calopteryx (damselfly)|''Calopteryx'']]
|Species (congeneric)
|2001
|Weekers et al.<ref>{{Cite journal|last1=Weekers|first1=Peter H. H.|last2=De Jonckheere|first2=Johan F.|last3=Dumont|first3=Henri J.|date=2001-07-01|title=Phylogenetic Relationships Inferred from Ribosomal ITS Sequences and Biogeographic Patterns in Representatives of the Genus ''Calopteryx'' (Insecta: Odonata) of the West Mediterranean and Adjacent West European Zone|journal=Molecular Phylogenetics and Evolution|volume=20|issue=1|pages=89–99|doi=10.1006/mpev.2001.0947|pmid=11421650}}</ref>
|-
| [[Yeasts]] of clinical importance
| Genera
| 2001
| Chen et al.<ref>{{cite journal | author=Chen, Y-C, J. D. Eisner, M. M. Kattar, S. L. Rassoulian-Barrett, K. Lafe, A. P. Limaye, and B. T. Cookson| title=Polymorphic Internal Transcribed Spacer Region 1 DNA Sequences Identify Medically Important Yeasts| journal=J. Clin. Microbiol.| year=2001 |doi= 10.1128/JCM.39.11.4042-4051.2001| pages=4042–4051|volume=39|pmid=11682528 | issue=11 | pmc=88485}}</ref>
|-
|[[Poaceae]]: Saccharinae
|Genera (within tribes)
|2002
|Hodkinson et al.<ref>{{Cite journal|last1=Hodkinson|first1=Trevor R.|last2=Chase|first2=Mark W.|last3=Lledó|first3=Dolores M.|last4=Salamin|first4=Nicolas|last5=Renvoize|first5=Stephen A.|year=2002|title=Phylogenetics of ''Miscanthus'', ''Saccharum'' and related genera (Saccharinae, Andropogoneae, Poaceae) based on DNA sequences from ITS nuclear ribosomal DNA and plastid trnL intron and trnL-F intergenic spacers|journal=Journal of Plant Research|volume=115|issue=5|pages=381–392|doi=10.1007/s10265-002-0049-3|pmid=12579363|bibcode=2002JPlR..115..381H |s2cid=22971617|issn=0918-9440}}</ref>
|-
|[[Plantaginaceae]]: ''[[Plantago]]''
|Species (congeneric)
|2002
|Rønsted et al.<ref>{{Cite journal|last1=Rønsted|first1=Nina|last2=Chase|first2=Mark W.|last3=Albach|first3=Dirk C.|last4=Bello|first4=Maria Angelica|date=2002-08-01|title=Phylogenetic relationships within ''Plantago'' (Plantaginaceae): evidence from nuclear ribosomal ITS and plastid trnL-F sequence data|journal=Botanical Journal of the Linnean Society|volume=139|issue=4|pages=323–338|doi=10.1046/j.1095-8339.2002.00070.x|issn=1095-8339|doi-access=free}}</ref>
|-
|[[Jungermanniopsida]]: ''[[Herbertus]]''
|Species (congeneric)
|2004
|Feldberg et al.<ref>{{Cite journal|last1=Feldberg|first1=K.|last2=Groth|first2=H.|last3=Wilson|first3=R.|last4=Schäfer-Verwimp|first4=A.|last5=Heinrichs|first5=J.|date=2004-11-04|title=Cryptic speciation in ''Herbertus'' (Herbertaceae, Jungermanniopsida): Range and morphology of Herbertus sendtneri inferred from nrITS sequences|journal=Plant Systematics and Evolution|volume=249|issue=3–4|pages=247–261|doi=10.1007/s00606-004-0221-4|bibcode=2004PSyEv.249..247F |s2cid=21538862|issn=0378-2697}}</ref>
|-
|[[Pinaceae]]: ''[[Tsuga]]''
|Species (congeneric)
|2008
|Havill et al.<ref>{{Cite journal|last1=Havill|first1=Nathan P.|author-link1=Nathan Havill |last2=Campbell|first2=Christopher S.|last3=Vining|first3=Thomas F.|last4=LePage|first4=Ben|last5=Bayer|first5=Randall J.|last6=Donoghue|first6=Michael J.|date=2008-07-01|title=Phylogeny and Biogeography of ''Tsuga'' (Pinaceae) Inferred from Nuclear Ribosomal ITS and Chloroplast DNA Sequence Data|journal=Systematic Botany|volume=33|issue=3|pages=478–489|doi=10.1600/036364408785679770|s2cid=26668467}}</ref>
|-
|[[Altica|Chrysomelidae: ''Altica'']] 
|Genera (congeneric)
|2009
|Ruhl et al.<ref>{{Cite journal|last1=Ruhl|first1=Michael W.|last2=Wolf|first2=Matthias|last3=Jenkins|first3=Tracie M.|date=2010|title=Compensatory base changes illuminate morphologically difficult taxonomy|url=https://www.academia.edu/attachments/47449213/download_file?st=MTU4MTYwMTYxNCw5OC4xOTIuNDIuMjg%3D&s=profile|journal=Molecular Phylogenetics and Evolution|language=en|volume=54|issue=2|pages=664–669|doi=10.1016/j.ympev.2009.07.036|pmid=19660561}}</ref>
|-
|''[[Symbiodinium]]''
|Clade
|2009
|Stat et al.<ref>{{Cite journal|last1=Stat|first1=Michael|last2=Pochon|first2=Xavier|date=2008-07-02|title=Specificity in communities of ''Symbiodinium'' in corals from Johnston Atoll|url=https://www.int-res.com/articles/meps2009/386/m386p083.pdf|journal=Marine Ecology Progress Series|volume=386|pages=83–96|doi=10.3354/meps08080|doi-access=free}}</ref>
|-
|[[Brassicaceae]]
|Tribes (within a family)
|2010
|Warwick et al.<ref>{{Cite journal|last1=Warwick|first1=Suzanne I.|last2=Mummenhoff|first2=Klaus|last3=Sauder|first3=Connie A.|last4=Koch|first4=Marcus A.|last5=Al-Shehbaz|first5=Ihsan A.|date=2010-04-13|title=Closing the gaps: phylogenetic relationships in the Brassicaceae based on DNA sequence data of nuclear ribosomal ITS region|journal=Plant Systematics and Evolution|volume=285|issue=3–4|pages=209–232|doi=10.1007/s00606-010-0271-8|bibcode=2010PSyEv.285..209W |s2cid=28199415|issn=0378-2697}}</ref>
|-
|[[Ericaceae]]: ''[[Erica (plant)|Erica]]''
|Species (congeneric)
|2011
|Pirie et al.<ref>{{Cite journal|last1=Pirie|first1=Michael D.|last2=Oliver|first2=E. G. H.|last3=Bellstedt|first3=Dirk U.|date=2011-11-01|title=A densely sampled ITS phylogeny of the Cape flagship genus ''Erica'' L. suggests numerous shifts in floral macro-morphology|journal=Molecular Phylogenetics and Evolution|volume=61|issue=2|pages=593–601|doi=10.1016/j.ympev.2011.06.007|pmid=21722743}}</ref>
|-
|[[Fly|Diptera]]: ''[[Bactrocera]]''
|Species (congeneric)
|2014
|Boykin et al.<ref>{{Cite journal|last1=Boykin|first1=L. M.|last2=Schutze|first2=M. K.|last3=Krosch|first3=M. N.|last4=Chomič|first4=A.|last5=Chapman|first5=T. A.|last6=Englezou|first6=A.|last7=Armstrong|first7=K. F.|last8=Clarke|first8=A. R.|last9=Hailstones|first9=D.|date=2014-05-01|title=Multi-gene phylogenetic analysis of south-east Asian pest members of the ''Bactrocera dorsalis'' species complex (Diptera: Tephritidae) does not support current taxonomy|journal=Journal of Applied Entomology|volume=138|issue=4|pages=235–253|doi=10.1111/jen.12047|s2cid=82003038|issn=1439-0418}}</ref>
|-
|[[Scrophulariaceae]]: ''[[Scrophularia]]''
|Species (congeneric)
|2014
|Scheunert & Heubl<ref>{{Cite journal|last1=Scheunert|first1=Agnes|last2=Heubl|first2=Günther|date=2014-01-01|title=Diversification of ''Scrophularia'' (Scrophulariaceae) in the Western Mediterranean and Macaronesia – Phylogenetic relationships, reticulate evolution and biogeographic patterns|journal=Molecular Phylogenetics and Evolution|volume=70|pages=296–313|doi=10.1016/j.ympev.2013.09.023|pmid=24096055}}</ref>
|-
|[[Potamogetonaceae]]: ''[[Potamogeton]]''
|Species (congeneric)
|2016
|Yang et al.<ref>{{Cite journal|last1=Yang|first1=Tao|last2=Zhang|first2=Tian-lei|last3=Guo|first3=You-hao|last4=Liu|first4=Xing|date=2016-11-17|title=Identification of Hybrids in ''Potamogeton'': Incongruence between Plastid and ITS Regions Solved by a Novel Barcoding Marker PHYB|journal=PLOS ONE|volume=11|issue=11|pages=e0166177|doi=10.1371/journal.pone.0166177|issn=1932-6203|pmc=5113904|pmid=27855191|bibcode=2016PLoSO..1166177Y|doi-access=free}}</ref>
|}

ITS2 is known to be more conserved than ITS1 is. All ITS2 sequences share a common core of secondary structure,<ref>{{cite journal |last1=Schultz |first1=J |last2=Maisel |first2=S |last3=Gerlach |first3=D |last4=Müller |first4=T |last5=Wolf |first5=M |title=A common core of secondary structure of the internal transcribed spacer 2 (ITS2) throughout the Eukaryota. |journal=RNA |date=April 2005 |volume=11 |issue=4 |pages=361–4 |doi=10.1261/rna.7204505 |pmid=15769870 |pmc=1370725}}</ref> while ITS1 structures are only conserved in much smaller taxonomic units. Regardless of the scope of conservation, structure-assisted comparison can provide higher resolution and robustness.<ref>{{cite journal |last1=Koetschan |first1=C |last2=Kittelmann |first2=S |last3=Lu |first3=J |last4=Al-Halbouni |first4=D |last5=Jarvis |first5=GN |last6=Müller |first6=T |last7=Wolf |first7=M |last8=Janssen |first8=PH |title=Internal transcribed spacer 1 secondary structure analysis reveals a common core throughout the anaerobic fungi (Neocallimastigomycota). |journal=PLOS ONE |date=2014 |volume=9 |issue=3 |pages=e91928 |doi=10.1371/journal.pone.0091928 |pmid=24663345 |pmc=3963862 |bibcode=2014PLoSO...991928K |doi-access=free}}</ref>

=== Mycological barcoding ===
{{Main|Fungal DNA barcoding}}
The ITS region is the most widely sequenced DNA region in [[molecular ecology]] of [[fungi]]<ref>{{cite journal |author1=Peay K.G. |author2=Kennedy P.G. |author3=Bruns T.D. | title=Fungal community ecology: a hybrid beast with a molecular master| journal=BioScience| year=2008 |pages=799–810|volume=58|issue=9 | doi=10.1641/b580907|s2cid=18363490 |doi-access=free }}</ref> and has been recommended as the universal fungal [[DNA barcoding|barcode]] sequence.<ref>{{cite journal | author=Schoch, C.L., Seifert, K.A., Huhndorf, S., Robert, V., Spouge, J.L., Levesque, C.A., Chen, W., Bolchacova, E., Voigt, K., Crous, P.W. | title=Nuclear Ribosomal Internal Transcribed Spacer (ITS) Region as a Universal DNA Barcode Marker for Fungi | journal=PNAS| year=2012 |doi= 10.1073/pnas.1117018109| pages=6241–6246|volume=109 | issue=16|display-authors=etal | pmid=22454494 | pmc=3341068| doi-access=free }}</ref> It has typically been most useful for molecular systematics at the species to genus level, and even within species (e.g., to identify geographic races). Because of its higher degree of variation than other genic regions of rDNA (for example, small- and large-subunit rRNA), variation among individual rDNA repeats can sometimes be observed within both the ITS and IGS regions. In addition to the universal ITS1+ITS4 primers<ref>White, T.J., Bruns, T., Lee, S., and Taylor, J. (1990). Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. PCR Protocols: a Guide to Methods and Applications 18, 315–322.</ref><ref>The ITS1 primer covers ITS1-5.8S-ITS2 from the 5', and ITS4 covers the same area from the 3'.</ref> used by many labs, several taxon-specific primers have been described that allow selective amplification of fungal sequences (e.g., see Gardes & Bruns 1993 paper describing amplification of [[basidiomycete]] ITS sequences from [[mycorrhiza]] samples).<ref>{{cite journal |author1=Gardes, M. |author2=Bruns, T.D.| title=ITS primers with enhanced specificity for basidiomycetes: application to the identification of mycorrhiza and rusts| journal=Molecular Ecology| year=1993 |doi= 10.1111/j.1365-294X.1993.tb00005.x| pages=113–118|volume=2|pmid=8180733 | issue=2|s2cid=24316407}}</ref> Despite [[shotgun sequencing]] methods becoming increasingly utilized in microbial sequencing, the low biomass of fungi in clinical samples make the ITS region amplification an area of ongoing research.<ref>{{Cite journal|last1=Usyk|first1=Mykhaylo|last2=Zolnik|first2=Christine P.|last3=Patel|first3=Hitesh|last4=Levi|first4=Michael H.|last5=Burk|first5=Robert D.|date=2017-12-13|editor-last=Mitchell|editor-first=Aaron P.|title=Novel ITS1 Fungal Primers for Characterization of the Mycobiome|journal=mSphere|volume=2|issue=6|pages=e00488–17, /msphere/2/6/mSphere0488–17.atom|doi=10.1128/mSphere.00488-17|issn=2379-5042|pmc=5729218|pmid=29242834}}</ref><ref>{{Cite journal|last1=Nilsson|first1=R. Henrik|last2=Anslan|first2=Sten|last3=Bahram|first3=Mohammad|last4=Wurzbacher|first4=Christian|last5=Baldrian|first5=Petr|last6=Tedersoo|first6=Leho|date=February 2019|title=Mycobiome diversity: high-throughput sequencing and identification of fungi|journal=Nature Reviews Microbiology|volume=17|issue=2|pages=95–109|doi=10.1038/s41579-018-0116-y|pmid=30442909|s2cid=53438777|issn=1740-1534}}</ref>

== References ==
{{reflist|30em}}

== External links ==
* [http://depts.washington.edu/molmicdx/mdx/tests/yeast.shtml University of Washington Laboratory Medicine: Molecular Diagnosis | Yeast Sequencing]
* [http://itsonedb.cloud.ba.infn.it/ ITSone DB]
* [https://bio.tools/its2 ITS2 database] (Schultz et al.)

{{DEFAULTSORT:Internal Transcribed Spacer}}
[[Category:DNA]]
[[Category:Phylogenetics]]