Ribosomal DNA

Last updated

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 an promotor specific to the RNA polymerase I, as well as both transcribed and non-transcribed spacer segments.

Contents

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

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)
Plastid16S rRNA23S 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

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

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

Eukaryotes

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. Eucaryot rdna.png
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. Nucleolus (including pre-rRNA components).png
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

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

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

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

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

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

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]

Related Research Articles

<span class="mw-page-title-main">Genome</span> All genetic material of an organism

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

<span class="mw-page-title-main">Nucleolus</span> Largest structure in the nucleus of eukaryotic cells

The nucleolus is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of signal recognition particles and plays a role in the cell's response to stress. Nucleoli are made of proteins, DNA and RNA, and form around specific chromosomal regions called nucleolar organizing regions. Malfunction of the Golgi apparatus means that nucleocid is the cause of several human conditions called "nucleolopathies" and the nucleolus is being investigated as a target for cancer chemotherapy.

Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules. Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional, such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Regions that are completely nonfunctional are called junk DNA.

An inverted repeat is a single stranded sequence of nucleotides followed downstream by its reverse complement. The intervening sequence of nucleotides between the initial sequence and the reverse complement can be any length including zero. For example, 5'---TTACGnnnnnnCGTAA---3' is an inverted repeat sequence. When the intervening length is zero, the composite sequence is a palindromic sequence.

Internal transcribed spacer (ITS) is the spacer DNA situated between the small-subunit ribosomal RNA (rRNA) and large-subunit rRNA genes in the chromosome or the corresponding transcribed region in the polycistronic rRNA precursor transcript.

<span class="mw-page-title-main">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins, though this ratio differs between prokaryotes and eukaryotes.

RNA polymerase 1 is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA, a type of RNA that accounts for over 50% of the total RNA synthesized in a cell.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

Eukaryotic chromosome fine structure refers to the structure of sequences for eukaryotic chromosomes. Some fine sequences are included in more than one class, so the classification listed is not intended to be completely separate.

<span class="mw-page-title-main">Ribosome biogenesis</span> Cellular process

Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. It involves the coordinated function of over 200 proteins in the synthesis and processing of the three prokaryotic or four eukaryotic rRNAs, as well as assembly of those rRNAs with the ribosomal proteins. Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases. About 60% of a cell's energy is spent on ribosome production and maintenance.

<span class="mw-page-title-main">Gene cluster</span>

A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are often located within a few thousand base pairs of each other. The size of gene clusters can vary significantly, from a few genes to several hundred genes. Portions of the DNA sequence of each gene within a gene cluster are found to be identical; however, the resulting protein of each gene is distinctive from the resulting protein of another gene within the cluster. Genes found in a gene cluster may be observed near one another on the same chromosome or on different, but homologous chromosomes. An example of a gene cluster is the Hox gene, which is made up of eight genes and is part of the Homeobox gene family.

<span class="mw-page-title-main">5S ribosomal RNA</span> RNA component of the large subunit of the ribosome

The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation coefficient in an ultracentrifuge, which is measured in Svedberg units (S).

RNR4 is a human ribosomal DNA gene located on Chromosome 21. Tandem copies of this gene form one of five nucleolus organizer regions in the human genome, they are located on the chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21, 22 (RNR5).

RNR1 is a human ribosomal DNA gene located on Chromosome 13. Tandem copies of this gene form one of five nucleolus organizer regions in the human genome, they are located on the chromosomes 13, 14 (RNR2), 15 (RNR3), 21 (RNR4), 22 (RNR5).

RNR3 is a human ribosomal DNA gene located on Chromosome 15. Tandem copies of this gene form one of five nucleolus organizer regions in the human genome, they are located on the chromosomes 13 (RNR1), 14 (RNR2), 15, 21 (RNR4), 22 (RNR5).

RNR5 is a human ribosomal DNA gene located on Chromosome 22. Tandem copies of this gene form one of five nucleolus organizer regions in the human genome, they are located on the chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21 (RNR4), 22 . Each gene cluster contains 30–40 copies and encodes a 45S RNA product that is then cleaved to form 18S, 5.8S and 28S rRNA subunits. In general, genes for RNA remain poorly annotated in most large public databases.

18S ribosomal RNA is a part of the ribosomal RNA in eukaryotes. It is a component of the Eukaryotic small ribosomal subunit (40S) and the cytosolic homologue of both the 12S rRNA in mitochondria and the 16S rRNA in plastids and prokaryotes. Similar to the prokaryotic 16S rRNA, the genes of the 18S ribosomal RNA haven been widely used for phylogenetic studies and biodiversity screening of eukaryotes.

<span class="mw-page-title-main">Concerted evolution</span>

Concerted evolution is the phenomenon where paralogous genes within one species are more closely related to one another than to members of the same gene family in closely related species. In other terms, when specific members of a family are investigated, a greater amount of similarity is found within a species rather than between species. This is suggesting that members within this family do not in fact evolve independently of one another.

<span class="mw-page-title-main">Short interspersed nuclear element</span>

Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. SINEs compose about 13% of the mammalian genome.

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including molecular genetics, biochemistry, and microbiology. It is split across two articles:

References

  1. 1 2 3 4 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. 1 2 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. 1 2 3 4 5 6 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. 1 2 3 4 5 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. 1 2 3 4 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. 1 2 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.