Jump to content

Ribosomal DNA: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
No edit summary
Tag: Reverted
Criedley (talk | contribs)
124 edits
m Fixed typo
Tags: Mobile edit Mobile app edit iOS app edit App section source
 
(24 intermediate revisions by 11 users not shown)
Line 1: Line 1:
{{Short description|Genes coding for ribosomal RNA}}
{{missing information|bacteria/organelle, archaea (rDNA operons — the euk ones are technically polycistronic too); canonical inclusion of 5S in these groups; plastid 4.5S; occurrence of nonclassical "unlinked" variants ({{PMID|31712737}})|date=October 2021}}
{{missing information|bacteria/organelle, archaea (rDNA operons — the euk ones are technically polycistronic too); canonical inclusion of 5S in these groups; plastid 4.5S; occurrence of nonclassical "unlinked" variants ({{PMID|31712737}})|date=October 2021}}

The '''ribosomal DNA''' (abbreviated '''rDNA''') consists of a group of [[ribosomal RNA]] encoding genes and related regulatory elements, and is widespread in similar configuration in all [[domain (biology)|domains]] of life. The ribosomal DNA encodes the non-coding [[ribosomal RNA]], integral structural elements in the assembly of [[ribosome]]s, its importance making it the most abundant section of RNA found in cells of [[eukaryote]]s.<ref name="Warmerdam2019" /> Additionally, these segments includes [[Regulation of gene expression|regulatory]] sections, such as a [[Promoter (genetics)|promotor]] specific to the [[RNA polymerase I]], as well as both transcribed and non-transcribed [[Spacer DNA|spacer]] segments.

Due to their high importance in the assembly of [[ribosome]]s for [[protein biosynthesis]], the rDNA genes are generally highly conserved in [[evolution|molecular evolution]]. The number of copies can vary considerably per species.<ref name="Warmerdam2019" /> Ribosomal DNA is widely used for [[Phylogenetics|phylogenetic]] studies.<ref name="Hillis">{{cite journal | vauthors = Hillis DM, Dixon MT | title = Ribosomal DNA: Molecular Evolution and Phylogenetic Inference | journal = The Quarterly Review of Biology | volume = 66 | issue = 4 | pages = 411–53 | date = December 1991 | pmid = 1784710 | doi = 10.1086/417338 | s2cid = 32027097 }}</ref><ref name="Weisburg">{{cite journal | vauthors = Weisburg WG, Barns SM, Pelletier DA, Lane DJ | title = 16S ribosomal DNA amplification for phylogenetic study | journal = Journal of Bacteriology | volume = 173 | issue = 2 | pages = 697–703 | date = January 1991 | pmid = 1987160 | pmc = 207061 | doi = 10.1128/jb.173.2.697-703.1991 }}</ref>

== Structure ==
{| class="wikitable floatright" style="text-align: center;"
|+ Genes of the ribosomal DNA
!'''Type'''
!'''[[SSU rRNA]]'''
!'''[[LSU rRNA]]'''
|-
| Eukaryotes
| [[18S ribosomal RNA|18S rRNA]]
| [[28S ribosomal RNA|28S rRNA]]<br/>[[5.8S ribosomal RNA|5.8S rRNA]]<br/>''[[5S ribosomal RNA|5S rRNA]]''
|-
| Bacteria
| [[16S ribosomal RNA|16S rRNA]]
| [[23S ribosomal RNA|23S rRNA]]<br/>[[5S ribosomal RNA|5S rRNA]]
|-
| Mitochondrial
| [[MT-RNR1|MT-RNR1 (12S rRNA)]]
| [[MT-RNR2|MT-RNR2 (16S rRNA)]]
|-
| Plastid
| 16S rRNA
| 23S rRNA<br/>4.5S rRNA<br/>5S rRNA
|}

The ribosomal DNA includes all genes coding for the non-coding structural [[ribosomal RNA]] molecules. Across all [[domain (biology)|domains]] of life, these are the structural sequences of the [[SSU rRNA|small subunit]] ([[16S ribosomal RNA|16S]] or [[18S ribosomal RNA|18S rRNA]]) and the [[LSU rRNA|large subunit]] ([[23S ribosomal RNA|23S]] or [[28S ribosomal RNA|28S rRNA]]). The assembly of the latter also include the [[5S ribosomal RNA|5S rRNA]] as well as the additional [[5.8S ribosomal RNA|5.8S rRNA]] in eukaryotes.

The rDNA-genes are commonly present with multiple copies in the genome, where they are organized in linked groups in most species, separated by an [[internal transcribed spacer|internal transcribed spacer (ITS)]] and preceded by the [[External transcribed spacer|External transcribed spacer (ETS)]]. The [[5S ribosomal RNA|5S rRNA]] is also linked to these rDNA region in [[#Prokaryotes|prokaryotes]], while it is located in separate repeating regions in most [[#Eukaryotes|eukaryotes]].<ref name=Graw2015Springer>{{cite book |last=Graw |first=Jochen |date=2015|edition=6th |title=Genetik |trans-title=Genetics |language=German |location=Berlin, Heidelberg |publisher= Springer-Verlag Berlin Heidelberg|isbn=978-3-662-44816-8|doi=10.1007/978-3-662-44817-5}}</ref> They are transcribed together to a precursor RNA which is then processed to equal amounts of each rRNA.

=== Prokaryotes ===
The primary structural rRNA molecules in [[Bacteria]] and [[Archaea]] are smaller than their counterparts in eukaryotes, grouped as [[16S ribosomal RNA|16S rRNA]] and [[23S ribosomal RNA|23S rRNA]]. Meanwhile, the [[5S ribosomal RNA|5S rRNA]] also present in prokaryotes, is of a similar size to eukaryotes.

A notable amount of bacteria and archaea diverge from the canonical structure of the operon containing the rDNA genes, carrying the "unlinked" genes in different places of their genome.<ref name=Brewer2020>{{cite journal | vauthors = Brewer TE, Albertsen M, Edwards A, Kirkegaard RH, Rocha EP, Fierer N | title = Unlinked rRNA genes are widespread among bacteria and archaea | journal = The ISME Journal | volume = 14 | issue = 2 | pages = 597–608 | date = February 2020 | doi = 10.1038/s41396-019-0552-3 | pmid= 31712737 | pmc =6976660| bibcode = 2020ISMEJ..14..597B }}</ref>

==== Plastids ====
Ribosomal DNA in [[chloroplasts]] follows the structure of prokaryotic ribosomal DNA.

=== Eukaryotes ===
[[Image:Eucaryot rdna.png|thumb|400px|right|The gene segment of eukaryotic rDNA contains 18S, 5.8S, and 28S tracts and forms a tandem repetitive cluster; the 5S rDNA is coded separately.
[[Image:Eucaryot rdna.png|thumb|400px|right|The gene segment of eukaryotic rDNA contains 18S, 5.8S, and 28S tracts and forms a tandem repetitive cluster; the 5S rDNA is coded separately.
'''NTS''', nontranscribed spacer, '''ETS''', external transcribed spacer, '''ITS''', [[internal transcribed spacer]]s 1 and 2, numbered from 5' end.]]
'''NTS''', nontranscribed spacer, '''ETS''', [[external transcribed spacer]], '''ITS''', [[internal transcribed spacer]]s 1 and 2, numbered from 5' end.]]
[[File:Nucleolus (including pre-rRNA components).png|thumb|Nucleolus with pre-rRNA components called Introns and Exons. ]]
[[File:Nucleolus (including pre-rRNA components).png|thumb|Nucleolus with pre-rRNA components called Introns and Exons.]]

'''Ribosomal DNA''' ('''rDNA''') is a [[DNA]] sequence that codes for [[ribosomal RNA]]. These sequences regulate [[Transcription (genetics)|transcription]] initiation and amplification, and contain both transcribed and non-transcribed [[Spacer DNA|spacer]] segments.
The rDNA gene cluster of eukaryotes consists of the genes for the [[18S ribosomal RNA|18S]], [[5.8S ribosomal RNA|5.8S]] and [[28S ribosomal RNA|28S rRNA]], separated by the two [[internal transcribed spacer|ITS-1 and ITS-2]] spacers. The active genome of eukaryotes contains several hundred copies of the rDNA transcriptional unit as [[Tandemly arrayed genes|tandem repeats]], they are organized in [[Nucleolus organizer region|nucleolus organizer regions (NORs)]],<ref name=Graw2015Springer/> which in turn can be present at multiple [[Locus (genetics)|loci]] in the genome.<ref name=Richard2008/>

Similar to the structure of prokaryotes, the [[5S ribosomal RNA|5S rRNA]] is appended to the rDNA cluster in the [[Saccharomycetes|Saccharomycetes (Hemiascomycetes)]]<ref name=Richard2008/> such as ''[[Saccharomyces cerevisiae]]''.<ref name=Graw2015Springer/> Most eukaryotes however, carry the gene for the [[5S ribosomal RNA|5S rRNA]] in separate gene repeats at different loci in the genome.<ref name=Richard2008>{{cite journal | vauthors = Richard GF, Kerrest A, Dujon B | 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><ref name=Graw2015Springer/>

5S rDNA is also present in independent tandem repeats as in ''[[Drosophila]]''.<ref name=Richard2008/>
As repetitive DNA regions often undergo recombination events, the rDNA repeats have many regulatory mechanisms that keep the DNA from undergoing mutations,{{Example needed|date=July 2024}} thus keeping the rDNA conserved.<ref name="Warmerdam2019">{{Cite journal|last1=Warmerdam|first1=Daniël O.|last2=Wolthuis|first2=Rob M. F.|date=2019-03-01|title=Keeping ribosomal DNA intact: a repeating challenge|journal=Chromosome Research |language=en|volume=27|issue=1|pages=57–72 |doi=10.1007/s10577-018-9594-z|issn=1573-6849|pmc=6394564|pmid=30556094}}</ref>


⚫
In the nucleus, the [[nucleolus organizer region]]s give rise to the [[nucleolus]], where the rDNA regions of the chromosome forms expanded chromosomal loops, accessible for transcription of [[rRNA]]. In rDNA, the tandem repeats are mostly found in the nucleolus; but heterochromatic rDNA is found outside of the nucleolus. However, transcriptionally active rDNA resides inside of the nucleolus itself.<ref name="Warmerdam2019" />
In the [[human genome]] there are 5 chromosomes with nucleolus organizer regions: the [[Centromere#Acrocentric|acrocentric]] chromosomes 13 ([[RNR1]]), 14 ([[RNR2]]), 15 ([[RNR3]]), 21 ([[RNR4]]) and 22 ([[RNR5]]). The genes that are responsible for encoding the various sub-units of rRNA are located across multiple chromosomes in humans. But the genes that encode for rRNA are highly conserved across the domains, with only the copy numbers involved for the genes having varying numbers per species.<ref name="Rob" /> In [[Bacteria]], [[Archaea]], and [[chloroplasts]] the rRNA is composed of different (smaller) units, the [[23S ribosomal RNA|large (23S) ribosomal RNA]], [[16S ribosomal RNA]] and 5S rRNA. The 16S rRNA is widely used for [[Phylogenetics|phylogenetic]] studies.<ref name="Weisburg">{{cite journal | vauthors = Weisburg WG, Barns SM, Pelletier DA, Lane DJ | title = 16S ribosomal DNA amplification for phylogenetic study | journal = Journal of Bacteriology | volume = 173 | issue = 2 | pages = 697–703 | date = January 1991 | pmid = 1987160 | pmc = 207061 | doi = 10.1128/jb.173.2.697-703.1991 }}</ref>


== Eukaryotes ==
====Humans====
The [[human genome]] contains a total of 560 copies<ref name=Graw2015Springer/> of the rDNA transcriptional unit, spread across five chromosomes with [[nucleolus organizer region]]s. The repeat clusters are located on the [[Centromere#Acrocentric|acrocentric]] chromosomes 13 ([[RNR1]]), 14 ([[RNR2]]), 15 ([[RNR3]]), 21 ([[RNR4]]) and 22 ([[RNR5]]).<ref name=Schmidt2017Springer>{{cite book |last=Schmidt |first=Olaf |editor-last=Fritsche |editor-first=Olaf |date=2017 |title=Genetik und Molekularbiologie |trans-title=Genetics and molecular biology |series=Kompaktwissen Biologie |language=German |location=Berlin, Heidelberg |publisher= Springer-Verlag Berlin Heidelberg |isbn=978-3-662-50273-0 |doi=10.1007/978-3-662-50274-7}}</ref>
The rRNA transcribed from the approximately 600 r[[DNA repeat]]s forms the most abundant section of RNA found in cells of [[eukaryote]]s.<ref name="Rob" /> [[Ribosome]]s are assemblies of proteins and rRNA molecules that [[Translation (biology)|translate]] [[Messenger RNA|mRNA]] molecules to produce proteins. As shown in the figure, rDNA of eukaryotes consists of a [[Tandemly arrayed genes|tandem repeat]] of a unit segment, composed of NTS, ETS, [[18S ribosomal RNA|18S]], [[ITS1]], [[5.8S]], [[ITS2]], and [[28S]] tracts. rDNA has another gene, coding for [[5S ribosomal RNA|5S]] rRNA, located in the genome in most eukaryotes.<ref name=Richard>{{cite journal | vauthors = Richard GF, Kerrest A, Dujon B | 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> 5S rDNA is also present in independent tandem repeats as in ''[[Drosophila]]''.<ref name=Richard/> DNA regions that are repetitive often undergo recombination events. The rDNA repeats have many regulatory mechanisms that keep the DNA from undergoing mutations, thus keeping the rDNA conserved.<ref name="Rob">{{Cite journal|last=Warmerdam|first=Daniël O.|last2=Wolthuis|first2=Rob M. F.|date=2019-03-01|title=Keeping ribosomal DNA intact: a repeating challenge|journal=Chromosome Research|language=en|volume=27|issue=1|pages=57–72|doi=10.1007/s10577-018-9594-z|issn=1573-6849|pmc=6394564|pmid=30556094}}</ref>


====Ciliates====
⚫
In the nucleus, the rDNA region of the chromosome is visualized as a [[nucleolus]] which forms expanded chromosomal loops with rDNA. The rRNA transcriptional units are clustered in tandem repeats. These rDNA regions are also called [[nucleolus organizer region]]s, as they give rise to the nucleolus. In rDNA, the tandem repeats are mostly found in the nucleolus; but heterochromatic rDNA is found outside of the nucleolus. However, transcriptionally active rDNA resides inside of the nucleolus itself.<ref name="Rob" />
In [[ciliate]]s, the presence of a generative [[micronucleus]] next to the vegetative [[macronucleus]] allows for the reduction of rDNA genes in the germline. The exact number of copies in the micronucleus core genome ranging from several copies in ''[[Paramecium]]''<ref name="Prescott1994"/> as low as a single copy in ''[[Tetrahymena thermophila]]''<ref name=Graw2015Springer/> and other ''[[Tetrahymena]]'' species. During [[macronucleus]] formation, the regions containing the rDNA gene clusters are amplified, dramatically increasing the amount of available templates for transcription up to several thousand copies. In some ciliate genera, such as ''[[Tetrahymena]]'' or the [[Hypotrich]] genus ''[[Oxytricha]]'',<ref name="Prescott1994"/> extensive fragmentation of the amplified DNA leads to the formation of microchromosomes, centered on the rDNA transcriptional unit.<ref name="Prescott1994">{{Cite journal|last1=Prescott |first1=David M. |date=June 1994 |title=The DNA of Ciliated Protozoa |journal=Microbiological Reviews |language=en|volume=58|issue=2|pages=233–267 |doi=10.1128/mr.58.2.233-267.1994 |pmc= 372963 |pmid= 8078435}}</ref> Similar processes are reported from ''[[Glaucoma chattoni]]'' and to lesser extent from ''[[Paramecium]]''.<ref name="Prescott1994"/>


== Sequence homogeneity ==
== Sequence homogeneity ==


In the large rDNA array, polymorphisms between rDNA repeat units are very low, indicating that rDNA tandem arrays are evolving through [[concerted evolution]].<ref name=Richard/> However, the mechanism of concerted evolution is imperfect, such that polymorphisms between repeats within an individual can occur at significant levels and may confound [[Phylogenetics|phylogenetic]] analyses for closely related organisms.<ref name="Álvarez">{{cite journal | vauthors = Alvarez I, Wendel JF | title = Ribosomal ITS sequences and plant phylogenetic inference | journal = Molecular Phylogenetics and Evolution | volume = 29 | issue = 3 | pages = 417–34 | date = December 2003 | pmid = 14615184 | doi = 10.1016/S1055-7903(03)00208-2 }}</ref><ref name=Weitemier>{{cite journal | vauthors = Weitemier K, Straub SC, Fishbein M, Liston A | title = Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae) | journal = PeerJ | volume = 3 | pages = e718 | date = 2015 | pmid = 25653903 | pmc = 4304868 | doi = 10.7717/peerj.718 }}</ref>
In the large rDNA array, polymorphisms between rDNA repeat units are very low, indicating that rDNA tandem arrays are evolving through [[concerted evolution]].<ref name=Richard2008/> However, the mechanism of concerted evolution is imperfect, such that polymorphisms between repeats within an individual can occur at significant levels and may confound [[Phylogenetics|phylogenetic]] analyses for closely related organisms.<ref name="Álvarez">{{cite journal | vauthors = Alvarez I, Wendel JF | title = Ribosomal ITS sequences and plant phylogenetic inference | journal = Molecular Phylogenetics and Evolution | volume = 29 | issue = 3 | pages = 417–34 | date = December 2003 | pmid = 14615184 | doi = 10.1016/S1055-7903(03)00208-2 | bibcode = 2003MolPE..29..417A }}</ref><ref name=Weitemier>{{cite journal | vauthors = Weitemier K, Straub SC, Fishbein M, Liston A | title = Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae) | journal = PeerJ | volume = 3 | pages = e718 | date = 2015 | pmid = 25653903 | pmc = 4304868 | doi = 10.7717/peerj.718 | doi-access = free }}</ref>


5S tandem repeat sequences in several ''Drosophila'' were compared with each other; the result revealed that [[Insertion (genetics)|insertion]]s and [[Deletion (genetics)|deletion]]s occurred frequently between species and often flanked by conserved sequences.<ref name=Paques>{{cite journal | vauthors = Päques F, Samson ML, Jordan P, Wegnez M | title = Structural evolution of the Drosophila 5S ribosomal genes | journal = Journal of Molecular Evolution | volume = 41 | issue = 5 | pages = 615–21 | date = November 1995 | pmid = 7490776 | doi = 10.1007/bf00175820 | bibcode = 1995JMolE..41..615P }}</ref> They could occur by slippage of the newly synthesized strand during DNA replication or by gene conversion.<ref name=Paques/>
5S tandem repeat sequences in several ''Drosophila'' were compared with each other; the result revealed that [[Insertion (genetics)|insertion]]s and [[Deletion (genetics)|deletion]]s occurred frequently between species and often flanked by conserved sequences.<ref name=Paques>{{cite journal | vauthors = Päques F, Samson ML, Jordan P, Wegnez M | title = Structural evolution of the Drosophila 5S ribosomal genes | journal = Journal of Molecular Evolution | volume = 41 | issue = 5 | pages = 615–21 | date = November 1995 | pmid = 7490776 | doi = 10.1007/bf00175820 | bibcode = 1995JMolE..41..615P | s2cid = 6911205 }}</ref> They could occur by slippage of the newly synthesized strand during DNA replication or by gene conversion.<ref name=Paques/>


== Sequence divergence ==
== Sequence divergence ==
The rDNA transcription tracts have low rate of [[Gene polymorphism|polymorphism]] among species, which allows interspecific comparison to elucidate phylogenetic relationship using only a few specimens. Coding regions of rDNA are highly conserved among species but ITS regions are variable due to insertions, deletions, and point mutations. Between remote species as human and frog comparison of sequences at ITS tracts is not appropriate.<ref name=Sumida>{{cite journal | vauthors = Sumida M, Kato Y, Kurabayashi A | title = Sequencing and analysis of the internal transcribed spacers (ITSs) and coding regions in the EcoR I fragment of the ribosomal DNA of the Japanese pond frog Rana nigromaculata | journal = Genes & Genetic Systems | volume = 79 | issue = 2 | pages = 105–18 | date = April 2004 | pmid = 15215676 | doi = 10.1266/ggs.79.105 | doi-access = free }}</ref> Conserved sequences at coding regions of rDNA allow comparisons of remote species, even between yeast and human. Human 5.8S rRNA has 75% identity with yeast 5.8S rRNA.<ref name=Nazar>{{cite journal | vauthors = Nazar RN, Sitz TO, Busch H | title = Sequence homologies in mammalian 5.8S ribosomal RNA | journal = Biochemistry | volume = 15 | issue = 3 | pages = 505–8 | date = February 1976 | pmid = 1252408 | doi = 10.1021/bi00648a008 }}</ref>
The rDNA transcription tracts have low rate of [[Gene polymorphism|polymorphism]] among species, which allows interspecific comparison to elucidate phylogenetic relationship using only a few specimens. Coding regions of rDNA are highly conserved among species but ITS regions are variable due to insertions, deletions, and point mutations. Between remote species as human and frog comparison of sequences at ITS tracts is not appropriate.<ref name=Sumida>{{cite journal | vauthors = Sumida M, Kato Y, Kurabayashi A | title = Sequencing and analysis of the internal transcribed spacers (ITSs) and coding regions in the EcoR I fragment of the ribosomal DNA of the Japanese pond frog Rana nigromaculata | journal = Genes & Genetic Systems | volume = 79 | issue = 2 | pages = 105–18 | date = April 2004 | pmid = 15215676 | doi = 10.1266/ggs.79.105 | doi-access = free }}</ref> Conserved sequences at coding regions of rDNA allow comparisons of remote species, even between yeast and human. Human 5.8S rRNA has 75% identity with yeast 5.8S rRNA.<ref name=Nazar>{{cite journal | vauthors = Nazar RN, Sitz TO, Busch H | title = Sequence homologies in mammalian 5.8S ribosomal RNA | journal = Biochemistry | volume = 15 | issue = 3 | pages = 505–8 | date = February 1976 | pmid = 1252408 | doi = 10.1021/bi00648a008 }}</ref>
In cases for sibling species, comparison of the rDNA segment including ITS tracts among species and phylogenetic analysis are made satisfactorily.<ref name=ma>{{cite journal | vauthors = Fengyi MY, Jiannong X, Zheming Z | year = 1998 | title = Sequence differences of rDNA-ITS2 and species-diagnostic PCR assay of ''Anopheles sinensis'' and ''Anopheles anthropophagus'' from China | url = https://docs.google.com/viewer?url=http://www.mosquitocatalog.org/files/pdfs/MQ0115.pdf | journal = J Med Coll PLA | volume = 13 | pages = 123–128 }}</ref><ref name=Li>{{cite journal | last1 = Li | first1 = C | last2 = Lee | first2 = JS | last3 = Groebner | first3 = JL | last4 = Kim | first4 = HC | last5 = Klein | first5 = TA | last6 = O'Guinn | first6 = ML | last7 = Wilkerson | first7 = RC | year = 2005 | title = A newly recognized species in the ''Anopheles'' hyrcanus group and molecular identification of related species from the Republic of South Korea (Diptera: Culicidae) | url = https://apps.dtic.mil/sti/pdfs/ADA505037.pdf | archive-url = https://web.archive.org/web/20121001222507/http://www.dtic.mil/cgi-bin/GetTRDoc?Location=U2&doc=GetTRDoc.pdf&AD=ADA505037 | url-status = live | archive-date = October 1, 2012 | journal = Zootaxa | volume = 939 | pages = 1–8 | doi=10.11646/zootaxa.939.1.1| doi-access = free }}</ref>
In cases for sibling species, comparison of the rDNA segment including ITS tracts among species and phylogenetic analysis are made satisfactorily.<ref name=ma>{{cite journal | vauthors = Fengyi MY, Jiannong X, Zheming Z | year = 1998 | title = Sequence differences of rDNA-ITS2 and species-diagnostic PCR assay of ''Anopheles sinensis'' and ''Anopheles anthropophagus'' from China | url = https://docs.google.com/viewer?url=http://www.mosquitocatalog.org/files/pdfs/MQ0115.pdf | journal = J Med Coll PLA | volume = 13 | pages = 123–128 }}</ref><ref name=Li>{{cite journal | last1 = Li | first1 = C | last2 = Lee | first2 = JS | last3 = Groebner | first3 = JL | last4 = Kim | first4 = HC | last5 = Klein | first5 = TA | last6 = O'Guinn | first6 = ML | last7 = Wilkerson | first7 = RC | year = 2005 | title = A newly recognized species in the ''Anopheles'' hyrcanus group and molecular identification of related species from the Republic of South Korea (Diptera: Culicidae) | url = https://apps.dtic.mil/sti/pdfs/ADA505037.pdf | archive-url = https://web.archive.org/web/20121001222507/http://www.dtic.mil/cgi-bin/GetTRDoc?Location=U2&doc=GetTRDoc.pdf&AD=ADA505037 | url-status = live | archive-date = October 1, 2012 | journal = Zootaxa | volume = 939 | pages = 1–8 | doi=10.11646/zootaxa.939.1.1| doi-access = free }}</ref>
The different coding regions of the rDNA repeats usually show distinct evolutionary rates. As a result, this DNA can provide phylogenetic information of species belonging to wide systematic levels.<ref name=Hillis>{{cite journal | vauthors = Hillis DM, Dixon MT | title = Ribosomal DNA: molecular evolution and phylogenetic inference | journal = The Quarterly Review of Biology | volume = 66 | issue = 4 | pages = 411–53 | date = December 1991 | pmid = 1784710 | doi = 10.1086/417338 | url = https://semanticscholar.org/paper/36b34a0bc68c5fe9c107efeb81b2b189a1ec87bb }}</ref>
The different coding regions of the rDNA repeats usually show distinct evolutionary rates. As a result, this DNA can provide phylogenetic information of species belonging to wide systematic levels.<ref name="Hillis"/>


== Recombination-stimulating activity ==
== Recombination-stimulating activity ==


A fragment of yeast rDNA containing the 5S gene, non-transcribed spacer DNA, and part of the 35S gene has localized cis-acting [[mitotic recombination]] stimulating activity.<ref name="pmid6094015">{{cite journal | vauthors = Keil RL, Roeder GS | title = Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae | journal = Cell | volume = 39 | issue = 2 Pt 1 | pages = 377–86 | date = December 1984 | pmid = 6094015 | doi = 10.1016/0092-8674(84)90016-3 | doi-access = free }}</ref> This DNA fragment contains a mitotic [[recombination hotspot]], referred to as HOT1. HOT1 expresses recombination-stimulating activity when it is inserted into novel locations in the yeast [[genome]]. HOT1 includes an [[RNA polymerase I]] (PolI) transcription [[Promoter (genetics)|promoter]] that catalyzes 35S [[Ribosomal RNA|ribosomal rRNA]] gene transcription. In a PolI defective mutant, the HOT1 hotspot recombination-stimulating activity is abolished. The level of PolI transcription in HOT1 appears to determine the level of [[Genetic recombination|recombination]].<ref name="pmid15066122">{{cite journal | vauthors = Serizawa N, Horiuchi T, Kobayashi T | title = Transcription-mediated hyper-recombination in HOT1 | journal = Genes to Cells | volume = 9 | issue = 4 | pages = 305–15 | date = April 2004 | pmid = 15066122 | doi = 10.1111/j.1356-9597.2004.00729.x | doi-access = free }}</ref>
A fragment of yeast rDNA containing the 5S gene, non-transcribed spacer DNA, and part of the 35S gene has localized cis-acting [[mitotic recombination]] stimulating activity.<ref name="pmid6094015">{{cite journal | vauthors = Keil RL, Roeder GS | title = Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae | journal = Cell | volume = 39 | issue = 2 Pt 1 | pages = 377–86 | date = December 1984 | pmid = 6094015 | doi = 10.1016/0092-8674(84)90016-3 | doi-access = free }}</ref> This DNA fragment contains a mitotic [[recombination hotspot]], referred to as HOT1. HOT1 expresses recombination-stimulating activity when it is inserted into novel locations in the yeast [[genome]]. HOT1 includes an [[RNA polymerase I]] (PolI) transcription [[Promoter (genetics)|promoter]] that catalyzes 35S [[Ribosomal RNA|ribosomal rRNA]] gene transcription. In a PolI defective mutant, the HOT1 hotspot recombination-stimulating activity is abolished. The level of PolI transcription in HOT1 appears to determine the level of [[Genetic recombination|recombination]].<ref name="pmid15066122">{{cite journal | vauthors = Serizawa N, Horiuchi T, Kobayashi T | title = Transcription-mediated hyper-recombination in HOT1 | journal = Genes to Cells | volume = 9 | issue = 4 | pages = 305–15 | date = April 2004 | pmid = 15066122 | doi = 10.1111/j.1356-9597.2004.00729.x | doi-access = | s2cid = 23978914 }}</ref>


== Clinical significance ==
== Clinical significance ==
⚫
Diseases can be associated with DNA mutations where DNA can be expanded, such as [[Huntington's disease]], or lost due to deletion mutations. The same is true for mutations that occur in rDNA repeats; it has been found that if the genes that are associated with the synthesis of ribosomes are disrupted or mutated, it can result in various diseases associated with the skeleton or bone marrow. Also, any damage or disruption to the enzymes that protect the tandem repeats of the rDNA, can result in lower synthesis of ribosomes, which also lead to other defects in the cell. Neurological diseases can also arise from mutations in the rDNA tandem repeats, such as [[Bloom syndrome]], which occurs when the number of tandem repeats increases close to a hundred-fold; compared with that of the normal number of tandem repeats. Various types of cancers can also be born from mutations of the tandem repeats in the ribosomal DNA. Cell lines can become malignant from either a rearrangement of the tandem repeats, or an expansion of the repeats in the rDNA.<ref>{{cite journal | vauthors = Warmerdam DO, Wolthuis RM | title = Keeping ribosomal DNA intact: a repeating challenge | journal = Chromosome Research | volume = 27 | issue = 1–2 | pages = 57–72 | date = March 2019 | pmid = 30556094 | pmc = 6394564 | doi = 10.1007/s10577-018-9594-z }}</ref>
Diseases can be Rich Nguyen
⚫
associated with DNA mutations where DNA can be expanded, such as [[Huntington's disease]], or lost due to deletion mutations. The same is true for mutations that occur in rDNA repeats; it has been found that if the genes that are associated with the synthesis of ribosomes are disrupted or mutated, it can result in various diseases associated with the skeleton or bone marrow. Also, any damage or disruption to the enzymes that protect the tandem repeats of the rDNA, can result in lower synthesis of ribosomes, which also lead to other defects in the cell. Neurological diseases can also arise from mutations in the rDNA tandem repeats, such as [[Bloom syndrome]], which occurs when the number of tandem repeats increases close to a hundred-fold; compared with that of the normal number of tandem repeats. Various types of cancers can also be born from mutations of the tandem repeats in the ribosomal DNA. Cell lines can become malignant from either a rearrangement of the tandem repeats, or an expansion of the repeats in the rDNA.<ref>{{cite journal | vauthors = Warmerdam DO, Wolthuis RM | title = Keeping ribosomal DNA intact: a repeating challenge | journal = Chromosome Research | volume = 27 | issue = 1–2 | pages = 57–72 | date = March 2019 | pmid = 30556094 | pmc = 6394564 | doi = 10.1007/s10577-018-9594-z }}</ref>


== References ==
== References ==

Latest revision as of 01:38, 20 November 2024

The ribosomal DNA (abbreviated rDNA) consists of a group of ribosomal RNA encoding genes and related regulatory elements, and is widespread in similar configuration in all domains of life. The ribosomal DNA encodes the non-coding ribosomal RNA, integral structural elements in the assembly of ribosomes, its importance making it the most abundant section of RNA found in cells of eukaryotes.[1] Additionally, these segments includes regulatory sections, such as a promotor specific to the RNA polymerase I, as well as both transcribed and non-transcribed spacer segments.

Due to their high importance in the assembly of ribosomes for protein biosynthesis, the rDNA genes are generally highly conserved in molecular evolution. The number of copies can vary considerably per species.[1] Ribosomal DNA is widely used for phylogenetic studies.[2][3]

Structure

[edit]
Genes of the ribosomal DNA
Type SSU rRNA LSU rRNA
Eukaryotes 18S rRNA 28S rRNA
5.8S rRNA
5S rRNA
Bacteria 16S rRNA 23S rRNA
5S rRNA
Mitochondrial MT-RNR1 (12S rRNA) MT-RNR2 (16S rRNA)
Plastid 16S rRNA 23S rRNA
4.5S rRNA
5S rRNA

The ribosomal DNA includes all genes coding for the non-coding structural ribosomal RNA molecules. Across all domains of life, these are the structural sequences of the small subunit (16S or 18S rRNA) and the large subunit (23S or 28S rRNA). The assembly of the latter also include the 5S rRNA as well as the additional 5.8S rRNA in eukaryotes.

The rDNA-genes are commonly present with multiple copies in the genome, where they are organized in linked groups in most species, separated by an internal transcribed spacer (ITS) and preceded by the External transcribed spacer (ETS). The 5S rRNA is also linked to these rDNA region in prokaryotes, while it is located in separate repeating regions in most eukaryotes.[4] They are transcribed together to a precursor RNA which is then processed to equal amounts of each rRNA.

Prokaryotes

[edit]

The primary structural rRNA molecules in Bacteria and Archaea are smaller than their counterparts in eukaryotes, grouped as 16S rRNA and 23S rRNA. Meanwhile, the 5S rRNA also present in prokaryotes, is of a similar size to eukaryotes.

A notable amount of bacteria and archaea diverge from the canonical structure of the operon containing the rDNA genes, carrying the "unlinked" genes in different places of their genome.[5]

Plastids

[edit]

Ribosomal DNA in chloroplasts follows the structure of prokaryotic ribosomal DNA.

Eukaryotes

[edit]
The gene segment of eukaryotic rDNA contains 18S, 5.8S, and 28S tracts and forms a tandem repetitive cluster; the 5S rDNA is coded separately. NTS, nontranscribed spacer, ETS, external transcribed spacer, ITS, internal transcribed spacers 1 and 2, numbered from 5' end.
Nucleolus with pre-rRNA components called Introns and Exons.

The rDNA gene cluster of eukaryotes consists of the genes for the 18S, 5.8S and 28S rRNA, separated by the two ITS-1 and ITS-2 spacers. The active genome of eukaryotes contains several hundred copies of the rDNA transcriptional unit as tandem repeats, they are organized in nucleolus organizer regions (NORs),[4] which in turn can be present at multiple loci in the genome.[6]

Similar to the structure of prokaryotes, the 5S rRNA is appended to the rDNA cluster in the Saccharomycetes (Hemiascomycetes)[6] such as Saccharomyces cerevisiae.[4] Most eukaryotes however, carry the gene for the 5S rRNA in separate gene repeats at different loci in the genome.[6][4]

5S rDNA is also present in independent tandem repeats as in Drosophila.[6] As repetitive DNA regions often undergo recombination events, the rDNA repeats have many regulatory mechanisms that keep the DNA from undergoing mutations,[example needed] thus keeping the rDNA conserved.[1]

In the nucleus, the nucleolus organizer regions give rise to the nucleolus, where the rDNA regions of the chromosome forms expanded chromosomal loops, accessible for transcription of rRNA. In rDNA, the tandem repeats are mostly found in the nucleolus; but heterochromatic rDNA is found outside of the nucleolus. However, transcriptionally active rDNA resides inside of the nucleolus itself.[1]

Humans

[edit]

The human genome contains a total of 560 copies[4] of the rDNA transcriptional unit, spread across five chromosomes with nucleolus organizer regions. The repeat clusters are located on the acrocentric chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21 (RNR4) and 22 (RNR5).[7]

Ciliates

[edit]

In ciliates, the presence of a generative micronucleus next to the vegetative macronucleus allows for the reduction of rDNA genes in the germline. The exact number of copies in the micronucleus core genome ranging from several copies in Paramecium[8] as low as a single copy in Tetrahymena thermophila[4] and other Tetrahymena species. During macronucleus formation, the regions containing the rDNA gene clusters are amplified, dramatically increasing the amount of available templates for transcription up to several thousand copies. In some ciliate genera, such as Tetrahymena or the Hypotrich genus Oxytricha,[8] extensive fragmentation of the amplified DNA leads to the formation of microchromosomes, centered on the rDNA transcriptional unit.[8] Similar processes are reported from Glaucoma chattoni and to lesser extent from Paramecium.[8]

Sequence homogeneity

[edit]

In the large rDNA array, polymorphisms between rDNA repeat units are very low, indicating that rDNA tandem arrays are evolving through concerted evolution.[6] However, the mechanism of concerted evolution is imperfect, such that polymorphisms between repeats within an individual can occur at significant levels and may confound phylogenetic analyses for closely related organisms.[9][10]

5S tandem repeat sequences in several Drosophila were compared with each other; the result revealed that insertions and deletions occurred frequently between species and often flanked by conserved sequences.[11] They could occur by slippage of the newly synthesized strand during DNA replication or by gene conversion.[11]

Sequence divergence

[edit]

The rDNA transcription tracts have low rate of polymorphism among species, which allows interspecific comparison to elucidate phylogenetic relationship using only a few specimens. Coding regions of rDNA are highly conserved among species but ITS regions are variable due to insertions, deletions, and point mutations. Between remote species as human and frog comparison of sequences at ITS tracts is not appropriate.[12] Conserved sequences at coding regions of rDNA allow comparisons of remote species, even between yeast and human. Human 5.8S rRNA has 75% identity with yeast 5.8S rRNA.[13] In cases for sibling species, comparison of the rDNA segment including ITS tracts among species and phylogenetic analysis are made satisfactorily.[14][15] The different coding regions of the rDNA repeats usually show distinct evolutionary rates. As a result, this DNA can provide phylogenetic information of species belonging to wide systematic levels.[2]

Recombination-stimulating activity

[edit]

A fragment of yeast rDNA containing the 5S gene, non-transcribed spacer DNA, and part of the 35S gene has localized cis-acting mitotic recombination stimulating activity.[16] This DNA fragment contains a mitotic recombination hotspot, referred to as HOT1. HOT1 expresses recombination-stimulating activity when it is inserted into novel locations in the yeast genome. HOT1 includes an RNA polymerase I (PolI) transcription promoter that catalyzes 35S ribosomal rRNA gene transcription. In a PolI defective mutant, the HOT1 hotspot recombination-stimulating activity is abolished. The level of PolI transcription in HOT1 appears to determine the level of recombination.[17]

Clinical significance

[edit]

Diseases can be associated with DNA mutations where DNA can be expanded, such as Huntington's disease, or lost due to deletion mutations. The same is true for mutations that occur in rDNA repeats; it has been found that if the genes that are associated with the synthesis of ribosomes are disrupted or mutated, it can result in various diseases associated with the skeleton or bone marrow. Also, any damage or disruption to the enzymes that protect the tandem repeats of the rDNA, can result in lower synthesis of ribosomes, which also lead to other defects in the cell. Neurological diseases can also arise from mutations in the rDNA tandem repeats, such as Bloom syndrome, which occurs when the number of tandem repeats increases close to a hundred-fold; compared with that of the normal number of tandem repeats. Various types of cancers can also be born from mutations of the tandem repeats in the ribosomal DNA. Cell lines can become malignant from either a rearrangement of the tandem repeats, or an expansion of the repeats in the rDNA.[18]

References

[edit]
  1. ^ a b c d Warmerdam, Daniël O.; Wolthuis, Rob M. F. (2019-03-01). "Keeping ribosomal DNA intact: a repeating challenge". Chromosome Research. 27 (1): 57–72. doi:10.1007/s10577-018-9594-z. ISSN 1573-6849. PMC 6394564. PMID 30556094.
  2. ^ a b Hillis DM, Dixon MT (December 1991). "Ribosomal DNA: Molecular Evolution and Phylogenetic Inference". The Quarterly Review of Biology. 66 (4): 411–53. doi:10.1086/417338. PMID 1784710. S2CID 32027097.
  3. ^ Weisburg WG, Barns SM, Pelletier DA, Lane DJ (January 1991). "16S ribosomal DNA amplification for phylogenetic study". Journal of Bacteriology. 173 (2): 697–703. doi:10.1128/jb.173.2.697-703.1991. PMC 207061. PMID 1987160.
  4. ^ a b c d e f Graw, Jochen (2015). Genetik [Genetics] (in German) (6th ed.). Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg. doi:10.1007/978-3-662-44817-5. ISBN 978-3-662-44816-8.
  5. ^ Brewer TE, Albertsen M, Edwards A, Kirkegaard RH, Rocha EP, Fierer N (February 2020). "Unlinked rRNA genes are widespread among bacteria and archaea". The ISME Journal. 14 (2): 597–608. Bibcode:2020ISMEJ..14..597B. doi:10.1038/s41396-019-0552-3. PMC 6976660. PMID 31712737.
  6. ^ a b c d e Richard GF, Kerrest A, Dujon B (December 2008). "Comparative genomics and molecular dynamics of DNA repeats in eukaryotes". Microbiology and Molecular Biology Reviews. 72 (4): 686–727. doi:10.1128/MMBR.00011-08. PMC 2593564. PMID 19052325.
  7. ^ Schmidt, Olaf (2017). Fritsche, Olaf (ed.). Genetik und Molekularbiologie [Genetics and molecular biology]. Kompaktwissen Biologie (in German). Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg. doi:10.1007/978-3-662-50274-7. ISBN 978-3-662-50273-0.
  8. ^ a b c d Prescott, David M. (June 1994). "The DNA of Ciliated Protozoa". Microbiological Reviews. 58 (2): 233–267. doi:10.1128/mr.58.2.233-267.1994. PMC 372963. PMID 8078435.
  9. ^ Alvarez I, Wendel JF (December 2003). "Ribosomal ITS sequences and plant phylogenetic inference". Molecular Phylogenetics and Evolution. 29 (3): 417–34. Bibcode:2003MolPE..29..417A. doi:10.1016/S1055-7903(03)00208-2. PMID 14615184.
  10. ^ Weitemier K, Straub SC, Fishbein M, Liston A (2015). "Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae)". PeerJ. 3: e718. doi:10.7717/peerj.718. PMC 4304868. PMID 25653903.
  11. ^ a b Päques F, Samson ML, Jordan P, Wegnez M (November 1995). "Structural evolution of the Drosophila 5S ribosomal genes". Journal of Molecular Evolution. 41 (5): 615–21. Bibcode:1995JMolE..41..615P. doi:10.1007/bf00175820. PMID 7490776. S2CID 6911205.
  12. ^ Sumida M, Kato Y, Kurabayashi A (April 2004). "Sequencing and analysis of the internal transcribed spacers (ITSs) and coding regions in the EcoR I fragment of the ribosomal DNA of the Japanese pond frog Rana nigromaculata". Genes & Genetic Systems. 79 (2): 105–18. doi:10.1266/ggs.79.105. PMID 15215676.
  13. ^ Nazar RN, Sitz TO, Busch H (February 1976). "Sequence homologies in mammalian 5.8S ribosomal RNA". Biochemistry. 15 (3): 505–8. doi:10.1021/bi00648a008. PMID 1252408.
  14. ^ Fengyi MY, Jiannong X, Zheming Z (1998). "Sequence differences of rDNA-ITS2 and species-diagnostic PCR assay of Anopheles sinensis and Anopheles anthropophagus from China" (PDF). J Med Coll PLA. 13: 123–128.
  15. ^ Li, C; Lee, JS; Groebner, JL; Kim, HC; Klein, TA; O'Guinn, ML; Wilkerson, RC (2005). "A newly recognized species in the Anopheles hyrcanus group and molecular identification of related species from the Republic of South Korea (Diptera: Culicidae)" (PDF). Zootaxa. 939: 1–8. doi:10.11646/zootaxa.939.1.1. Archived from the original on October 1, 2012.
  16. ^ Keil RL, Roeder GS (December 1984). "Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae". Cell. 39 (2 Pt 1): 377–86. doi:10.1016/0092-8674(84)90016-3. PMID 6094015.
  17. ^ Serizawa N, Horiuchi T, Kobayashi T (April 2004). "Transcription-mediated hyper-recombination in HOT1". Genes to Cells. 9 (4): 305–15. doi:10.1111/j.1356-9597.2004.00729.x. PMID 15066122. S2CID 23978914.
  18. ^ Warmerdam DO, Wolthuis RM (March 2019). "Keeping ribosomal DNA intact: a repeating challenge". Chromosome Research. 27 (1–2): 57–72. doi:10.1007/s10577-018-9594-z. PMC 6394564. PMID 30556094.
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Ribosomal_DNA&oldid=1258494424"