Conserved non-coding sequence - Revision history

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	Repetitive elements can accumulate in an organism's genome as the result of a few different [[transposons\|transposition]] processes. The extent to which this has taken place during the evolution of eukaryotes varies greatly: repetitive DNA accounts for just 3% of the [[drosophila melanogaster\|fly]] genome, but accounts for 50% of the [[human genome]].<ref name="Jegga"/>		Repetitive elements can accumulate in an organism's genome as the result of a few different [[transposons\|transposition]] processes. The extent to which this has taken place during the evolution of eukaryotes varies greatly: repetitive DNA accounts for just 3% of the [[drosophila melanogaster\|fly]] genome, but accounts for 50% of the [[human genome]].<ref name="Jegga"/>

	There are different theories explaining the conservation of [[transposable element]]s. One holds that, like [[pseudogene]]s, they provide a source of new genetic material, allowing for faster [[adaptation]] to changes in the environment. A simpler alternative is that, because eukaryotic genomes may have no means to prevent the proliferation of transposable elements, they are free to accumulate as long as they are not inserted into or near a gene in such a way that they would disrupt essential functions.<ref name=Eickbush>{{Cite journal \| last1 = Eickbush \| first1 = TH. \| last2 = Eickbush \| first2 = DJ. \| title = Transposable Elements: Evolution. \| journal = eLS \|date=July 2006 \| doi = 10.1038/npg.els.0005130 \| isbn = 9780470016176 }}</ref> A recent study showed that transposons contribute at least 16% of the [[eutheria]]n-specific CNSs, marking them as a "major creative force" in the evolution of [[regulation of gene expression\|gene regulation]] in [[mammal]]s.<ref name=Mikkelsen>{{cite journal \| author=Mikkelsen, T.S.\| title=Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. \| journal=Nature \| year=2007 \| pages=167–177 \| volume=447\| issue=7141 \| pmid=17495919 \| doi=10.1038/nature05805\| bibcode=2007Natur.447..167M \|display-authors=etal\| doi-access=free }}</ref> There are three major classes of transposable elements, distinguished by the mechanisms by which they proliferate.<ref name="Eickbush"/>		There are different theories explaining the conservation of [[transposable element]]s. One holds that, like [[pseudogene]]s, they provide a source of new genetic material, allowing for faster [[adaptation]] to changes in the environment. A simpler alternative is that, because eukaryotic genomes may have no means to prevent the proliferation of transposable elements, they are free to accumulate as long as they are not inserted into or near a gene in such a way that they would disrupt essential functions.<ref name=Eickbush>{{Cite journal \| last1 = Eickbush \| first1 = TH. \| last2 = Eickbush \| first2 = DJ. \| title = Transposable Elements: Evolution. \| journal = eLS \|date=July 2006 \| doi = 10.1038/npg.els.0005130 \| isbn = 9780470016176 }}</ref> A recent study showed that transposons contribute at least 16% of the [[eutheria]]n-specific CNSs, marking them as a "major creative force" in the evolution of [[regulation of gene expression\|gene regulation]] in [[mammal]]s.<ref name=Mikkelsen>{{cite journal \| author=Mikkelsen, T.S.\| title=Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. \| journal=Nature \| year=2007 \| pages=167–177 \| volume=447\| issue=7141 \| pmid=17495919 \| doi=10.1038/nature05805\| bibcode=2007Natur.447..167M \|display-authors=etal\| doi-access=free \| hdl=1885/57171 \| hdl-access=free }}</ref> There are three major classes of transposable elements, distinguished by the mechanisms by which they proliferate.<ref name="Eickbush"/>

	====Classes====		====Classes====

81.191.81.174: /* Pseudogenes */

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Pseudogenes

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	===Pseudogenes===		===Pseudogenes===

	Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning [[orthologue]]s to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195 \| doi-access = free }}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>		Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning [[orthologue]]s to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its [[paralogous]] pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195 \| doi-access = free }}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>

	An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>		An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>

81.191.81.174: /* Pseudogenes */

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Pseudogenes

← Previous revision		Revision as of 00:09, 27 May 2024
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	===Pseudogenes===		===Pseudogenes===

	Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning ~~orthologues~~ to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195 \| doi-access = free }}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>		Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning [[orthologue]]s to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195 \| doi-access = free }}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>

	An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>		An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>

81.191.81.174: /* Classes */

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Classes

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	DNA transposons encode a [[transposase]] protein, which is flanked by [[inverted repeat]] sequences. The transposase excises the sequence and reintegrates it elsewhere in the genome. By excising immediately following [[DNA replication]] and inserting into target sites which have not yet been replicated, the number of transposons in the genome can increase.<ref name="Eickbush"/>		DNA transposons encode a [[transposase]] protein, which is flanked by [[inverted repeat]] sequences. The transposase excises the sequence and reintegrates it elsewhere in the genome. By excising immediately following [[DNA replication]] and inserting into target sites which have not yet been replicated, the number of transposons in the genome can increase.<ref name="Eickbush"/>

	[[Retrotransposon]]s use [[reverse transcriptase]] to generate a [[complementary dna\|cDNA]] from the TE transcript. These are further divided into [[long terminal repeat]] (LTR) retrotransposons, long interspersed nuclear ~~elements~~ (LINEs), and short interspersed nuclear ~~elements~~ (SINEs). In LTR retrotransposons, after the RNA template is degraded, a DNA strand complementary to the reverse-transcribed cDNA returns the element to a double-stranded state. [[Integrase]], an enzyme encoded by the LTR retrotransposon, then reincorporates the element at a new target site. These elements are flanked by long terminal repeats (300–500bp) which mediate the transposition process.<ref name="Eickbush"/>		[[Retrotransposon]]s use [[reverse transcriptase]] to generate a [[complementary dna\|cDNA]] from the TE transcript. These are further divided into [[long terminal repeat]] (LTR) retrotransposons, [[long interspersed nuclear element]]s (LINEs), and [[short interspersed nuclear element]]s (SINEs). In LTR retrotransposons, after the RNA template is degraded, a DNA strand complementary to the reverse-transcribed cDNA returns the element to a double-stranded state. [[Integrase]], an enzyme encoded by the LTR retrotransposon, then reincorporates the element at a new target site. These elements are flanked by long terminal repeats (300–500bp) which mediate the transposition process.<ref name="Eickbush"/>

	LINEs use a simpler method in which the cDNA is [[~~dna~~ synthesis\|synthesized]] at the target site following cleavage by a LINE-encoded [[endonuclease]]. LINE-encoded reverse transcriptase is not highly sequence-specific. The incorporation by LINE machinery of unrelated RNA transcripts gives rise to non-functional processed pseudogenes. If a small gene's [[promoter (biology)\|promoter]] is included in the transcribed portion of the gene, the stable transcript can be duplicated and reinserted into the genome multiple times. The elements produced by this process are called SINEs.<ref name="Eickbush"/>		LINEs use a simpler method in which the cDNA is [[DNA synthesis\|synthesized]] at the target site following cleavage by a LINE-encoded [[endonuclease]]. LINE-encoded reverse transcriptase is not highly sequence-specific. The incorporation by LINE machinery of unrelated RNA transcripts gives rise to non-functional processed pseudogenes. If a small gene's [[promoter (biology)\|promoter]] is included in the transcribed portion of the gene, the stable transcript can be duplicated and reinserted into the genome multiple times. The elements produced by this process are called SINEs.<ref name="Eickbush"/>

	====Conserved regulatory transposable elements====		====Conserved regulatory transposable elements====

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	==Ultraconserved regions==		==Ultraconserved regions==

	Ultraconserved regions (UCRs) are regions over 200 bp in length with 100% identity across species. These unique sequences are mostly found in noncoding regions. It is still not fully understood why the negative [[natural selection\|selective pressure]] on these regions is so much stronger than the selection in protein-coding regions.<ref name=Bejerano>{{Cite journal \| last1 = Bejerano \| first1 = G. \| last2 = Pheasant \| first2 = M. \| last3 = Makunin \| first3 = I. \| last4 = Stephen \| first4 = S. \| last5 = Kent \| first5 = W.J. \| last6 = Mattick \| first6 = J.S. \| last7 = Haussler \| first7 = David. \| title = Ultraconserved Elements in the Human Genome. \| journal = Science \| volume = 304 \| issue = 5675 \| pages = 1321–1325 \|date=May 2004 \| doi = 10.1126/science.1098119\| pmid = 15131266 \| bibcode = 2004Sci...304.1321B \| citeseerx = 10.1.1.380.9305 \| s2cid = 2790337 }}</ref><ref name=Katzman>{{Cite journal \| last1 = Katzman \| first1 = Sol. \| last2 = Kern \| first2 = A.D. \| last3 = Bejerano \| first3 = G. \| last4 = Fewell \| first4 = G. \| last5 = Fulton \| first5 = L. \| last6 = Wilson \| first6 = R.K. \| last7 = Salama \| first7 = S.R. \| last8 = Haussler \| first8 = David. \| title = Human Genome Ultraconserved Elements are Ultraselected. \| journal = Science \| volume = 317 \| issue = 5840 \| pages = 915 \|date=Aug 2007 \| doi = 10.1126/science.1142430\| pmid = 17702936 \| bibcode = 2007Sci...317..915K \| s2cid = 35322654 ~~\| url = https://semanticscholar.org/paper/bfafb2f217075db2ab0cefcdaabfa6596d1b7b6d~~ }}</ref> Though these regions can be seen as unique, the distinction between regions with a high degree of sequence conservation and those with perfect sequence conservation is not necessarily one of biological significance. One study in Science found that all extremely conserved noncoding sequences have important regulatory functions regardless of whether the conservation is perfect, making the distinction of ultraconservation appear somewhat arbitrary.<ref name="Katzman"/>		Ultraconserved regions (UCRs) are regions over 200 bp in length with 100% identity across species. These unique sequences are mostly found in noncoding regions. It is still not fully understood why the negative [[natural selection\|selective pressure]] on these regions is so much stronger than the selection in protein-coding regions.<ref name=Bejerano>{{Cite journal \| last1 = Bejerano \| first1 = G. \| last2 = Pheasant \| first2 = M. \| last3 = Makunin \| first3 = I. \| last4 = Stephen \| first4 = S. \| last5 = Kent \| first5 = W.J. \| last6 = Mattick \| first6 = J.S. \| last7 = Haussler \| first7 = David. \| title = Ultraconserved Elements in the Human Genome. \| journal = Science \| volume = 304 \| issue = 5675 \| pages = 1321–1325 \|date=May 2004 \| doi = 10.1126/science.1098119\| pmid = 15131266 \| bibcode = 2004Sci...304.1321B \| citeseerx = 10.1.1.380.9305 \| s2cid = 2790337 }}</ref><ref name=Katzman>{{Cite journal \| last1 = Katzman \| first1 = Sol. \| last2 = Kern \| first2 = A.D. \| last3 = Bejerano \| first3 = G. \| last4 = Fewell \| first4 = G. \| last5 = Fulton \| first5 = L. \| last6 = Wilson \| first6 = R.K. \| last7 = Salama \| first7 = S.R. \| last8 = Haussler \| first8 = David. \| title = Human Genome Ultraconserved Elements are Ultraselected. \| journal = Science \| volume = 317 \| issue = 5840 \| pages = 915 \|date=Aug 2007 \| doi = 10.1126/science.1142430\| pmid = 17702936 \| bibcode = 2007Sci...317..915K \| s2cid = 35322654 }}</ref> Though these regions can be seen as unique, the distinction between regions with a high degree of sequence conservation and those with perfect sequence conservation is not necessarily one of biological significance. One study in Science found that all extremely conserved noncoding sequences have important regulatory functions regardless of whether the conservation is perfect, making the distinction of ultraconservation appear somewhat arbitrary.<ref name="Katzman"/>

	==In comparative genomics==		==In comparative genomics==

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	! Program !! Website<ref name="Jegga"/>		! Program !! Website<ref name="Jegga"/>
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	\| Consite \|\| http://consite.genereg.net/		\| Consite \|\| http://consite.genereg.net/ {{Webarchive\|url=https://web.archive.org/web/20090105173530/http://consite.genereg.net/ \|date=2009-01-05 }}
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	\|http://ancora.genereg.net/		\|http://ancora.genereg.net/
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	\| FootPrinter \|\| http://bio.cs.washington.edu/software		\| FootPrinter \|\| http://bio.cs.washington.edu/software {{Webarchive\|url=https://web.archive.org/web/20111122214415/http://bio.cs.washington.edu/software \|date=2011-11-22 }}
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	\| GenomeTrafac \|\| http://genometrafac.cchmc.org/genome-trafac/index.jsp		\| GenomeTrafac \|\| http://genometrafac.cchmc.org/genome-trafac/index.jsp {{Webarchive\|url=https://web.archive.org/web/20200812151758/https://genometrafac.cchmc.org/genome-trafac/index.jsp \|date=2020-08-12 }}
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	===Pseudogenes===		===Pseudogenes===

	Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning orthologues to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195}}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>		Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning orthologues to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195 \| doi-access = free }}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>

	An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>		An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>
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	The regulatory functions commonly associated with conserved non-coding regions are thought to play a role in the evolution of eukaryotic complexity. On average, plants contain fewer CNSs per gene than mammals. This is thought to be related to their having undergone more polyploidization, or genome duplication events. During the subfunctionalization that ensues following gene duplication, there is potential for a greater rate of CNS loss per gene. Thus, genome duplication events may account for the fact that plants have more genes, each with fewer CNSs. Assuming the number of CNSs to be a proxy for regulatory complexity, this may account for the disparity in complexity between plants and mammals.<ref name=Lockton>{{Cite journal \| last1 = Lockton \| first1 = Steven. \| last2 = Gaut \| first2 = BS. \| title =Plant conserved non-coding sequences and paralogue evolution. \| journal = Trends in Genetics \| volume = 21 \| issue = 1 \| pages = 60–65 \|date=Jan 2005 \| doi = 10.1016/j.tig.2004.11.013 \| pmid = 15680516 }}</ref>		The regulatory functions commonly associated with conserved non-coding regions are thought to play a role in the evolution of eukaryotic complexity. On average, plants contain fewer CNSs per gene than mammals. This is thought to be related to their having undergone more polyploidization, or genome duplication events. During the subfunctionalization that ensues following gene duplication, there is potential for a greater rate of CNS loss per gene. Thus, genome duplication events may account for the fact that plants have more genes, each with fewer CNSs. Assuming the number of CNSs to be a proxy for regulatory complexity, this may account for the disparity in complexity between plants and mammals.<ref name=Lockton>{{Cite journal \| last1 = Lockton \| first1 = Steven. \| last2 = Gaut \| first2 = BS. \| title =Plant conserved non-coding sequences and paralogue evolution. \| journal = Trends in Genetics \| volume = 21 \| issue = 1 \| pages = 60–65 \|date=Jan 2005 \| doi = 10.1016/j.tig.2004.11.013 \| pmid = 15680516 }}</ref>

	Because changes in gene regulation are thought to account for most of the differences between humans and chimpanzees, researchers have looked to CNSs to try to show this. A portion of the CNSs between humans and other primates have an enrichment of human-specific [[single-nucleotide polymorphism]]s, suggesting positive selection for these SNPs and accelerated evolution of those CNSs. Many of these SNPs are also associated with changes in gene expression, suggesting that these CNSs played an important role in [[human evolution]].<ref name=Bird>{{cite journal \| author=Bird, Christine P.\| title=Fast-evolving noncoding sequences in the human genome. \| journal= Genome Biology \| year=2007 \| pages=R118\| volume= 8\| issue=6 \| pmid=17578567 \| doi=10.1186/gb-2007-8-6-r118 \| pmc=2394770\|display-authors=etal}}</ref>		Because changes in gene regulation are thought to account for most of the differences between humans and chimpanzees, researchers have looked to CNSs to try to show this. A portion of the CNSs between humans and other primates have an enrichment of human-specific [[single-nucleotide polymorphism]]s, suggesting positive selection for these SNPs and accelerated evolution of those CNSs. Many of these SNPs are also associated with changes in gene expression, suggesting that these CNSs played an important role in [[human evolution]].<ref name=Bird>{{cite journal \| author=Bird, Christine P.\| title=Fast-evolving noncoding sequences in the human genome. \| journal= Genome Biology \| year=2007 \| pages=R118\| volume= 8\| issue=6 \| pmid=17578567 \| doi=10.1186/gb-2007-8-6-r118 \| pmc=2394770\|display-authors=etal \| doi-access=free }}</ref>

	==Online bioinformatic software==		==Online bioinformatic software==

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← Previous revision		Revision as of 15:04, 31 March 2022
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	A '''conserved non-coding sequence''' ('''CNS''') is a [[DNA sequence]] of [[noncoding DNA]] that is [[evolution]]arily [[Conserved sequence\|conserved]]. These sequences are of interest for their potential to [[gene regulation\|regulate gene production]].<ref name =Hardison>{{Cite journal \| last1 = Hardison \| first1 = RC. \| title = Conserved noncoding sequences are reliable guides to regulatory elements. \| journal = Trends Genet \| volume = 16 \| issue = 9 \| pages = 369–72 \| date = Sep 2000 \| doi = 10.1016/s0168-9525(00)02081-3 \| pmid = 10973062 \| url = http://www.euchromatin.org/Hardison1.htm \| access-date = 2011-02-18 \| archive-url = https://web.archive.org/web/20001204202400/http://www.euchromatin.org/Hardison1.htm \| archive-date = 2000-12-04 \| url-status = dead }}</ref>		A '''conserved non-coding sequence''' ('''CNS''') is a [[DNA sequence]] of [[noncoding DNA]] that is [[evolution]]arily [[Conserved sequence\|conserved]]. These sequences are of interest for their potential to [[gene regulation\|regulate gene production]].<ref name =Hardison>{{Cite journal \| last1 = Hardison \| first1 = RC. \| title = Conserved noncoding sequences are reliable guides to regulatory elements. \| journal = Trends Genet \| volume = 16 \| issue = 9 \| pages = 369–72 \| date = Sep 2000 \| doi = 10.1016/s0168-9525(00)02081-3 \| pmid = 10973062 \| url = http://www.euchromatin.org/Hardison1.htm \| access-date = 2011-02-18 \| archive-url = https://web.archive.org/web/20001204202400/http://www.euchromatin.org/Hardison1.htm \| archive-date = 2000-12-04 \| url-status = dead }}</ref>

	CNSs in plants<ref name=Freeling>{{Cite journal \| last1 = Freeling \| first1 = M \| last2 = Subramaniam \| first2 = S \| title = Conserved noncoding sequences (CNSs) in higher plants. \| journal = Curr Opin Plant Biol \| volume = 12 \| issue = 2 \| pages = 126–32\|date=Apr 2009 \| doi = 10.1016/j.pbi.2009.01.005 \| pmid = 19249238 }}</ref> and animals<ref name =Hardison/> are highly associated with [[transcription factor]] binding sites and other [[Cis-regulatory element\|''cis''-acting regulatory elements]]. Conserved non-coding sequences can be important sites of evolutionary divergence<ref name=Prabhakar>{{Cite journal \| last1 = Prabhakar \| first1 = S. \| last2 = Noonan \| first2 = JP. \| last3 = Pääbo \| first3 = S. \| last4 = Rubin \| first4 = EM. \| title = Accelerated evolution of conserved noncoding sequences in humans. \| journal = Science \| volume = 314 \| issue = 5800 \| pages = 786 \|date=Nov 2006 \| doi = 10.1126/science.1130738 \| pmid = 17082449 }}</ref> as mutations in these regions may alter the regulation of [[Conserved sequence\|conserved genes]], producing species-specific patterns of [[gene expression]]. These features have made them an invaluable resource in [[comparative genomics]].		CNSs in plants<ref name=Freeling>{{Cite journal \| last1 = Freeling \| first1 = M \| last2 = Subramaniam \| first2 = S \| title = Conserved noncoding sequences (CNSs) in higher plants. \| journal = Curr Opin Plant Biol \| volume = 12 \| issue = 2 \| pages = 126–32\|date=Apr 2009 \| doi = 10.1016/j.pbi.2009.01.005 \| pmid = 19249238 }}</ref> and animals<ref name =Hardison/> are highly associated with [[transcription factor]] binding sites and other [[Cis-regulatory element\|''cis''-acting regulatory elements]]. Conserved non-coding sequences can be important sites of evolutionary divergence<ref name=Prabhakar>{{Cite journal \| last1 = Prabhakar \| first1 = S. \| last2 = Noonan \| first2 = JP. \| last3 = Pääbo \| first3 = S. \| last4 = Rubin \| first4 = EM. \| title = Accelerated evolution of conserved noncoding sequences in humans. \| journal = Science \| volume = 314 \| issue = 5800 \| pages = 786 \|date=Nov 2006 \| doi = 10.1126/science.1130738 \| pmid = 17082449 \| s2cid = 15049725 }}</ref> as mutations in these regions may alter the regulation of [[Conserved sequence\|conserved genes]], producing species-specific patterns of [[gene expression]]. These features have made them an invaluable resource in [[comparative genomics]].

	==Sources==		==Sources==
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	Repetitive elements can accumulate in an organism's genome as the result of a few different [[transposons\|transposition]] processes. The extent to which this has taken place during the evolution of eukaryotes varies greatly: repetitive DNA accounts for just 3% of the [[drosophila melanogaster\|fly]] genome, but accounts for 50% of the [[human genome]].<ref name="Jegga"/>		Repetitive elements can accumulate in an organism's genome as the result of a few different [[transposons\|transposition]] processes. The extent to which this has taken place during the evolution of eukaryotes varies greatly: repetitive DNA accounts for just 3% of the [[drosophila melanogaster\|fly]] genome, but accounts for 50% of the [[human genome]].<ref name="Jegga"/>

	There are different theories explaining the conservation of [[transposable element]]s. One holds that, like [[pseudogene]]s, they provide a source of new genetic material, allowing for faster [[adaptation]] to changes in the environment. A simpler alternative is that, because eukaryotic genomes may have no means to prevent the proliferation of transposable elements, they are free to accumulate as long as they are not inserted into or near a gene in such a way that they would disrupt essential functions.<ref name=Eickbush>{{Cite journal \| last1 = Eickbush \| first1 = TH. \| last2 = Eickbush \| first2 = DJ. \| title = Transposable Elements: Evolution. \| journal = eLS \|date=July 2006 }}</ref> A recent study showed that transposons contribute at least 16% of the [[eutheria]]n-specific CNSs, marking them as a "major creative force" in the evolution of [[regulation of gene expression\|gene regulation]] in [[mammal]]s.<ref name=Mikkelsen>{{cite journal \| author=Mikkelsen, T.S.\| title=Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. \| journal=Nature \| year=2007 \| pages=167–177 \| volume=447\| issue=7141 \| pmid=17495919 \| doi=10.1038/nature05805\|display-authors=etal\| doi-access=free }}</ref> There are three major classes of transposable elements, distinguished by the mechanisms by which they proliferate.<ref name="Eickbush"/>		There are different theories explaining the conservation of [[transposable element]]s. One holds that, like [[pseudogene]]s, they provide a source of new genetic material, allowing for faster [[adaptation]] to changes in the environment. A simpler alternative is that, because eukaryotic genomes may have no means to prevent the proliferation of transposable elements, they are free to accumulate as long as they are not inserted into or near a gene in such a way that they would disrupt essential functions.<ref name=Eickbush>{{Cite journal \| last1 = Eickbush \| first1 = TH. \| last2 = Eickbush \| first2 = DJ. \| title = Transposable Elements: Evolution. \| journal = eLS \|date=July 2006 \| doi = 10.1038/npg.els.0005130 \| isbn = 9780470016176 }}</ref> A recent study showed that transposons contribute at least 16% of the [[eutheria]]n-specific CNSs, marking them as a "major creative force" in the evolution of [[regulation of gene expression\|gene regulation]] in [[mammal]]s.<ref name=Mikkelsen>{{cite journal \| author=Mikkelsen, T.S.\| title=Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. \| journal=Nature \| year=2007 \| pages=167–177 \| volume=447\| issue=7141 \| pmid=17495919 \| doi=10.1038/nature05805\| bibcode=2007Natur.447..167M \|display-authors=etal\| doi-access=free }}</ref> There are three major classes of transposable elements, distinguished by the mechanisms by which they proliferate.<ref name="Eickbush"/>

	====Classes====		====Classes====
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	===Pseudogenes===		===Pseudogenes===

	Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning orthologues to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = ~~PLoS~~ Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195}}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 }}</ref>		Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or [[mutation]]s. The primary evidence for this process is the presence of fully functioning orthologues to these inactivated sequences in other related genomes.<ref name="Jegga"/> Pseudogenes commonly emerge following a [[gene duplication]] or [[polyploid]]ization event. With two functional copies of a gene, there is no selective pressure to maintain expressibility of both, leaving one free to accumulate mutations as a nonfunctioning pseudogene. This is the typical case, whereby neutral selection allows pseudogenes to accumulate mutations, serving as "reservoirs" of new genetic material, with potential to be reincorporated into the genome. However, some pseudogenes have been found to be conserved in mammals.<ref>Cooper, DN. ''Human Gene Evolution''. Oxford: BIOS Scientific Publishers, Sept, 1988, p.265-292</ref> The simplest explanation for this is that these noncoding regions may serve some biological function, and this has been found to be the case for several conserved pseudogenes. Makorin1 mRNA, for example, was found to be stabilized by its paralogous pseudogene, Makorin1-p1, which is conserved in several mouse species. Other pseudogenes have also been found to be conserved between humans and mice and between humans and [[Common chimpanzee\|chimpanzee]]s, originating from duplication events prior to the [[speciation\|divergence of the species]]. Evidence of these pseudogenes' transcription also supports the hypothesis that they have a biological function.<ref name=Svensson>{{Cite journal \| last1 = Svensson \| first1 = O. \| last2 = Arvestad \| first2 = L. \| last3 = Lagergren \| first3 = J. \| title = Genome-wide survey for biologically functional pseudogenes. \| journal = PLOS Comput. Biol. \| volume = 2 \| issue = 5 \| page = 46 \|date=May 2005 \| doi = 10.1371/journal.pcbi.0020046 \|pmc=1456316 \|pmid=16680195}}</ref> Findings of potentially functional pseudogenes creates difficulty in defining them, since the term was originally meant for degenerate sequences with no biological function.<ref name=Podlaha>{{Cite journal \| last1 = Podlaha \| first1 = Ondrej. \| last2 = Zhang \| first2 = Jianzhi. \| title = Pseudogenes and Their Evolution. \| journal = eLS \|date=Nov 2010 \| doi = 10.1002/9780470015902.a0005118.pub2 \| isbn = 9780470016176 }}</ref>

	An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| pmid = 1400507 }}</ref>		An example of a pseudogene is the gene for [[L-gulonolactone oxidase]], a liver enzyme necessary for biosynthesis of L-ascorbic acid (vitamin C) in most birds and mammals, but which is mutated in the [[haplorrhini]] suborder of primates, including humans which require ascorbic acid or ascorbate from food. The remains of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.<ref name="pmid1400507">{{cite journal \|vauthors=Nishikimi M, Kawai T, Yagi K \| title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species \| journal = J. Biol. Chem. \| volume = 267 \| issue = 30 \| pages = 21967–72 \|date=October 1992 \| doi = 10.1016/S0021-9258(19)36707-9 \| pmid = 1400507 \| doi-access = free }}</ref>

	==Ultraconserved regions==		==Ultraconserved regions==

	Ultraconserved regions (UCRs) are regions over 200 bp in length with 100% identity across species. These unique sequences are mostly found in noncoding regions. It is still not fully understood why the negative [[natural selection\|selective pressure]] on these regions is so much stronger than the selection in protein-coding regions.<ref name=Bejerano>{{Cite journal \| last1 = Bejerano \| first1 = G. \| last2 = Pheasant \| first2 = M. \| last3 = Makunin \| first3 = I. \| last4 = Stephen \| first4 = S. \| last5 = Kent \| first5 = W.J. \| last6 = Mattick \| first6 = J.S. \| last7 = Haussler \| first7 = David. \| title = Ultraconserved Elements in the Human Genome. \| journal = Science \| volume = 304 \| issue = 5675 \| pages = 1321–1325 \|date=May 2004 \| doi = 10.1126/science.1098119\| pmid = 15131266 \| citeseerx = 10.1.1.380.9305 }}</ref><ref name=Katzman>{{Cite journal \| last1 = Katzman \| first1 = Sol. \| last2 = Kern \| first2 = A.D. \| last3 = Bejerano \| first3 = G. \| last4 = Fewell \| first4 = G. \| last5 = Fulton \| first5 = L. \| last6 = Wilson \| first6 = R.K. \| last7 = Salama \| first7 = S.R. \| last8 = Haussler \| first8 = David. \| title = Human Genome Ultraconserved Elements are Ultraselected. \| journal = Science \| volume = 317 \| issue = 5840 \| pages = 915 \|date=Aug 2007 \| doi = 10.1126/science.1142430\| pmid = 17702936 \| url = https://semanticscholar.org/paper/bfafb2f217075db2ab0cefcdaabfa6596d1b7b6d }}</ref> Though these regions can be seen as unique, the distinction between regions with a high degree of sequence conservation and those with perfect sequence conservation is not necessarily one of biological significance. One study in Science found that all extremely conserved noncoding sequences have important regulatory functions regardless of whether the conservation is perfect, making the distinction of ultraconservation appear somewhat arbitrary.<ref name="Katzman"/>		Ultraconserved regions (UCRs) are regions over 200 bp in length with 100% identity across species. These unique sequences are mostly found in noncoding regions. It is still not fully understood why the negative [[natural selection\|selective pressure]] on these regions is so much stronger than the selection in protein-coding regions.<ref name=Bejerano>{{Cite journal \| last1 = Bejerano \| first1 = G. \| last2 = Pheasant \| first2 = M. \| last3 = Makunin \| first3 = I. \| last4 = Stephen \| first4 = S. \| last5 = Kent \| first5 = W.J. \| last6 = Mattick \| first6 = J.S. \| last7 = Haussler \| first7 = David. \| title = Ultraconserved Elements in the Human Genome. \| journal = Science \| volume = 304 \| issue = 5675 \| pages = 1321–1325 \|date=May 2004 \| doi = 10.1126/science.1098119\| pmid = 15131266 \| bibcode = 2004Sci...304.1321B \| citeseerx = 10.1.1.380.9305 \| s2cid = 2790337 }}</ref><ref name=Katzman>{{Cite journal \| last1 = Katzman \| first1 = Sol. \| last2 = Kern \| first2 = A.D. \| last3 = Bejerano \| first3 = G. \| last4 = Fewell \| first4 = G. \| last5 = Fulton \| first5 = L. \| last6 = Wilson \| first6 = R.K. \| last7 = Salama \| first7 = S.R. \| last8 = Haussler \| first8 = David. \| title = Human Genome Ultraconserved Elements are Ultraselected. \| journal = Science \| volume = 317 \| issue = 5840 \| pages = 915 \|date=Aug 2007 \| doi = 10.1126/science.1142430\| pmid = 17702936 \| bibcode = 2007Sci...317..915K \| s2cid = 35322654 \| url = https://semanticscholar.org/paper/bfafb2f217075db2ab0cefcdaabfa6596d1b7b6d }}</ref> Though these regions can be seen as unique, the distinction between regions with a high degree of sequence conservation and those with perfect sequence conservation is not necessarily one of biological significance. One study in Science found that all extremely conserved noncoding sequences have important regulatory functions regardless of whether the conservation is perfect, making the distinction of ultraconservation appear somewhat arbitrary.<ref name="Katzman"/>

	==In comparative genomics==		==In comparative genomics==

	The conservation of both functional and nonfunctional noncoding regions provides an important tool for [[comparative genomics]], though conservation of cis-regulatory elements has proven particularly useful.<ref name="Jegga"/>		The conservation of both functional and nonfunctional noncoding regions provides an important tool for [[comparative genomics]], though conservation of cis-regulatory elements has proven particularly useful.<ref name="Jegga"/>
	The presence of CNSs could be due in some cases to a lack of divergence time,<ref name=Dubchak>{{Cite journal \| last1 = Dubchack \| first1 = I. \| last2 = Brudno \| first2 = M. \| last3 = Loots \| first3 = GG. \| last4 = Pachter \| first4 = L. \| author4-link = Lior Pachter \| last5 = Mayor \| first5 = C. \| last6 = Rubin \| first6 = EM. \| last7 = Frazer \| first7 = KA. \| title =Active Conservation of Noncoding Sequences Revealed by Three-Way Species Comparisons. \| journal = Genome Res. \| volume = 10 \| pages = 1304–1306 \| year = 2000 \| doi = 10.1101/gr.142200\| pmid = 10984448 \| issue=9 \| pmc=310906}}</ref> though the more common thinking is that they perform functions which place varying degrees of constraint on their evolution. Consistent with this theory, cis-regulatory elements are commonly found in conserved noncoding regions. Thus, sequence similarity is often used as a parameter to limit the search space when trying to identify regulatory elements conserved across species, though this is most useful in analyzing distantly related organisms, since closer relatives have sequence conservation among nonfunctional elements as well.<ref name="Jegga"/><ref name=Matsunami>{{Cite journal \| last1 = Matsunami \| first1 = M. \| last2 = Sumiyama \| first2 = K. \| last3 = Saitou \| first3 = N. \| title = Evolution of Conserved Non-Coding Sequences Within the Vertebrate Hox Clusters Through the Two-Round Whole Genome Duplications Revealed by Phylogenetic Footprinting Analysis. \| journal = Journal of Molecular Evolution \| volume = 71 \| issue = 5–6 \| pages = 427–463\|date=Sep 2010 \| doi = 10.1007/s00239-010-9396-1\| pmid = 20981416 }}</ref><ref name=Santini>{{Cite journal \| last1 = Santini \| first1 = S. \| last2 = Boore \| first2 = JL. \| last3 = Meyer \| first3 = A. \| title = Evolutionary Conservation of Regulatory Elements in Vertebrate Hox Gene Clusters. \| journal = Genome Res. \| volume = 13 \| pages = 1111–1122\| year = 2003 \| doi = 10.1101/gr.700503\| pmid = 12799348 \| issue=6A \| pmc=403639}}</ref>		The presence of CNSs could be due in some cases to a lack of divergence time,<ref name=Dubchak>{{Cite journal \| last1 = Dubchack \| first1 = I. \| last2 = Brudno \| first2 = M. \| last3 = Loots \| first3 = GG. \| last4 = Pachter \| first4 = L. \| author4-link = Lior Pachter \| last5 = Mayor \| first5 = C. \| last6 = Rubin \| first6 = EM. \| last7 = Frazer \| first7 = KA. \| title =Active Conservation of Noncoding Sequences Revealed by Three-Way Species Comparisons. \| journal = Genome Res. \| volume = 10 \| pages = 1304–1306 \| year = 2000 \| doi = 10.1101/gr.142200\| pmid = 10984448 \| issue=9 \| pmc=310906}}</ref> though the more common thinking is that they perform functions which place varying degrees of constraint on their evolution. Consistent with this theory, cis-regulatory elements are commonly found in conserved noncoding regions. Thus, sequence similarity is often used as a parameter to limit the search space when trying to identify regulatory elements conserved across species, though this is most useful in analyzing distantly related organisms, since closer relatives have sequence conservation among nonfunctional elements as well.<ref name="Jegga"/><ref name=Matsunami>{{Cite journal \| last1 = Matsunami \| first1 = M. \| last2 = Sumiyama \| first2 = K. \| last3 = Saitou \| first3 = N. \| title = Evolution of Conserved Non-Coding Sequences Within the Vertebrate Hox Clusters Through the Two-Round Whole Genome Duplications Revealed by Phylogenetic Footprinting Analysis. \| journal = Journal of Molecular Evolution \| volume = 71 \| issue = 5–6 \| pages = 427–463\|date=Sep 2010 \| doi = 10.1007/s00239-010-9396-1\| pmid = 20981416 \| bibcode = 2010JMolE..71..427M \| s2cid = 9733304 }}</ref><ref name=Santini>{{Cite journal \| last1 = Santini \| first1 = S. \| last2 = Boore \| first2 = JL. \| last3 = Meyer \| first3 = A. \| title = Evolutionary Conservation of Regulatory Elements in Vertebrate Hox Gene Clusters. \| journal = Genome Res. \| volume = 13 \| pages = 1111–1122\| year = 2003 \| doi = 10.1101/gr.700503\| pmid = 12799348 \| issue=6A \| pmc=403639}}</ref>

	Orthologues with high sequence similarity may not share the same regulatory elements.<ref name=Greaves>{{cite journal \| author= Greaves, D.R.\| title=Functional Comparison of the Murine Macrosialin and Human CD68 Promoters in Macrophage and Nonmacrophage Cell Lines. \| journal= Genomics \| year=1998 \| pages=165–168\| volume= 54\| issue=1 \| pmid=9806844 \| doi=10.1006/geno.1998.5546\|display-authors=etal}}</ref> These differences may account for different expression patterns across species.<ref name=Marchese>{{cite journal \| author=Marchese, A.\| title= Mapping Studies of Two G Protein-Coupled Receptor Genes: An Amino Acid Difference May Confer a Functional Variation Between a Human and Rodent Receptor. \| journal= Biochem Biophys Res Commun \| year=1994 \| pages=1952–1958\| volume= 205\| issue=3 \| pmid=7811287 \| doi=10.1006/bbrc.1994.2899 \|display-authors=etal}}</ref> Conservation of noncoding sequence is important for the analysis of paralogs within a single species as well. CNSs shared by paralogous clusters of [[Hox gene]]s are candidates for expression regulating regions, possibly coordinating the similar expression patterns of these genes.<ref name="Matsunami"/>		Orthologues with high sequence similarity may not share the same regulatory elements.<ref name=Greaves>{{cite journal \| author= Greaves, D.R.\| title=Functional Comparison of the Murine Macrosialin and Human CD68 Promoters in Macrophage and Nonmacrophage Cell Lines. \| journal= Genomics \| year=1998 \| pages=165–168\| volume= 54\| issue=1 \| pmid=9806844 \| doi=10.1006/geno.1998.5546\|display-authors=etal}}</ref> These differences may account for different expression patterns across species.<ref name=Marchese>{{cite journal \| author=Marchese, A.\| title= Mapping Studies of Two G Protein-Coupled Receptor Genes: An Amino Acid Difference May Confer a Functional Variation Between a Human and Rodent Receptor. \| journal= Biochem Biophys Res Commun \| year=1994 \| pages=1952–1958\| volume= 205\| issue=3 \| pmid=7811287 \| doi=10.1006/bbrc.1994.2899 \|display-authors=etal}}</ref> Conservation of noncoding sequence is important for the analysis of paralogs within a single species as well. CNSs shared by paralogous clusters of [[Hox gene]]s are candidates for expression regulating regions, possibly coordinating the similar expression patterns of these genes.<ref name="Matsunami"/>

Floyd23: #suggestededit-add 1.0

2022-02-16T07:06:03Z

#suggestededit-add 1.0

← Previous revision		Revision as of 07:06, 16 February 2022
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			{{Short description\|DNA sequence}}
	A '''conserved non-coding sequence''' ('''CNS''') is a [[DNA sequence]] of [[noncoding DNA]] that is [[evolution]]arily [[Conserved sequence\|conserved]]. These sequences are of interest for their potential to [[gene regulation\|regulate gene production]].<ref name =Hardison>{{Cite journal \| last1 = Hardison \| first1 = RC. \| title = Conserved noncoding sequences are reliable guides to regulatory elements. \| journal = Trends Genet \| volume = 16 \| issue = 9 \| pages = 369–72 \| date = Sep 2000 \| doi = 10.1016/s0168-9525(00)02081-3 \| pmid = 10973062 \| url = http://www.euchromatin.org/Hardison1.htm \| access-date = 2011-02-18 \| archive-url = https://web.archive.org/web/20001204202400/http://www.euchromatin.org/Hardison1.htm \| archive-date = 2000-12-04 \| url-status = dead }}</ref>		A '''conserved non-coding sequence''' ('''CNS''') is a [[DNA sequence]] of [[noncoding DNA]] that is [[evolution]]arily [[Conserved sequence\|conserved]]. These sequences are of interest for their potential to [[gene regulation\|regulate gene production]].<ref name =Hardison>{{Cite journal \| last1 = Hardison \| first1 = RC. \| title = Conserved noncoding sequences are reliable guides to regulatory elements. \| journal = Trends Genet \| volume = 16 \| issue = 9 \| pages = 369–72 \| date = Sep 2000 \| doi = 10.1016/s0168-9525(00)02081-3 \| pmid = 10973062 \| url = http://www.euchromatin.org/Hardison1.htm \| access-date = 2011-02-18 \| archive-url = https://web.archive.org/web/20001204202400/http://www.euchromatin.org/Hardison1.htm \| archive-date = 2000-12-04 \| url-status = dead }}</ref>

Dabed: Added Category:Non-coding DNA

2021-09-01T21:38:25Z

Added Category:Non-coding DNA

← Previous revision		Revision as of 21:38, 1 September 2021
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	[[Category:DNA]]		[[Category:DNA]]
			[[Category:Non-coding DNA]]