Junk DNA 44297 223898664 2008-07-06T12:01:52Z SmackBot 433328 Date the maintenance tags or general fixes {{Cleanup|date=July 2008}} In [[molecular biology]], '''junk DNA''' is a provisional label for the portions of the [[DNA]] sequence of a [[chromosome]] or a [[genome]] for which no [[Function (biology)|function]] has been identified. Scientists expect to find functions for some, but not all, of this provisionally classified collection. About 80-90% of the [[human genome]] has been designated as "junk", including most sequences within [[intron]]s and most [[intergenic region|intergenic DNA]]. While much of this sequence may be an [[evolution]]ary artifact that serves no present-day purpose, some junk DNA may function in ways that are not currently understood. Moreover, the [[conservation (genetics)|conservation]] of some junk DNA over many millions of years of [[evolution]] may imply an essential function. Some consider the "junk" label as something of a [[misnomer]], but others consider it appropriate as junk is stored away for possible new uses, rather than thrown out; others prefer the term "[[noncoding DNA]]" (although junk DNA often includes [[transposons]] that encode proteins with no clear value to their host genome). About 80% of the bases in the human genome may be transcribed,<ref name ="DNAStudy">{{cite journal | author=Pennisi, Elizabeth |title =DNA Study Forces Rethink of What It Means to Be a Gene|journal = Science| volume = 316 | issue = 5831 | year = 2007 | pages =1556–7 |doi =10.1126/science.316.5831.1556 |pmid =17569836}}</ref> but transcription does not necessarily imply function. Broadly, the science of [[functional genomics]] has developed widely accepted techniques to characterize protein-coding [[gene]]s, [[RNA gene]]s, and [[regulatory regions]]. In the genomes of most [[plant]]s and [[animal]]s, however, these together constitute only a small percentage of genomic DNA (less than 2% in the case of humans). The function, if any, of the remainder remains under investigation. Most of it can be identified as [[Repeated sequence (DNA)|repetitive elements]] that have no known biological function for their host (although they are useful to geneticists for analyzing [[genealogical DNA test|lineage]] and [[phylogeny]]). Still, a large amount of sequence in these genomes falls under no existing classification other than "junk". For example, recent experiments removed 1% of the mouse genome and were unable to detect any effect on the [[phenotype]]<ref name=Nobrega>{{ cite journal | author=M.A. Nobrega, Y. Zhu, I. Plajzer-Frick, V. Afzal and E.M. Rubin | year=2004 | title=Megabase deletions of gene deserts result in viable mice | journal=[[Nature (journal)|Nature]] | volume=431 | pages=988-993 | doi=10.1038/nature03022 | issue=7011 }}</ref>. This result suggests that the DNA is nonfunctional. However, it remains a possibility that there is some function that the experiments performed on the mice were merely insufficient to detect. While overall [[genome size]], and by extension the amount of junk DNA, are correlated to organism complexity, it is not a solid rule of thumb. For example, the genome of the unicellular ''[[Amoeba dubia]]'' has been reported to contain more than 200 times the amount of DNA in humans"<ref name=Gregory>{{ cite journal | author=Gregory, T.R. and P.D.N. Hebert . | title=The modulation of DNA content: proximate causes and ultimate consequences | journal=Genome Research | year=1999 | pages=317-324 | volume=9 | }}</ref> <ref name=GregoryWeb>Gregory, T.R. (2005). Animal Genome Size Database. http://www.genomesize.com.</ref>. The [[pufferfish]] ''[[Fugu|Takifugu]] rubripes'' genome is only about one tenth the size of the human genome, yet seems to have a comparable number of genes. Most of the difference appears to lie in what is now known only as junk DNA. This puzzle is known as the ''[[C-value enigma]]'' or, more conventionally, the ''C-value paradox''<ref name=Wahls>{{ cite journal | author=Wahls, W.P., ''et al.'' | title=Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells | journal=Cell | year=1990 | pages=95-103 | volume=60 | issue=1 | pmid=2295091 }}</ref>. == Types of junk DNA == {{Expand-section|date=July 2008}} * [[Pseudogene]]s - Some chromosomal regions are composed of the now-defunct remains of ancient genes, known as pseudogenes, which were once functional copies of genes but have since lost their protein-coding ability (and, presumably, their biological function). After non-functionalization, pseudogenes are free to acquire genetic noise in the form of random mutations. * [[Retrotransposon]]s - 8% of the human genome has been shown to be formed by retrotransposons of [[Endogenous retrovirus|Human Endogenous Retroviruses]] (HERVs)<ref name=Blaise>{{ cite journal | author=S. Blaise , N. de Parseval and T. Heidmann | year=2005 | title=Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes | journal=Retrovirology | volume=2 | doi=10.1186/1742-4690-2-19 | issue=19 }}</ref>, although as much as 25% is recognisably formed of retrotransposons<ref name=Deininger>{{ cite journal | author=P.L. Deininger, M.A. Batzer | month=October | year=2002 | title=Mammalian retroelements | journal=Genome Res. | volume=12 | pages=1455-1465 | pmid=12368238 | issue=10 }}</ref>. This is a lower limit on how much of the genome is retrotransposons because older remains might not be recognizable having accumulated too much mutation. New research suggests that genome size variation in at least two kinds of plants is mostly because of retrotransposons.<ref>[http://www.genome.org/cgi/content/short/16/10/1252] [http://www.genome.org/cgi/content/short/16/10/1262?]</ref> == Hypotheses of origin and function == There are some hypotheses, none conclusively established for how junk DNA arose and why it persists in the genome: * Junk DNA might provide a reservoir of sequences from which potentially advantageous new genes can emerge. In this way, it may be an important genetic basis for evolution<ref>"<cite>...Professor Christina Cheng's group from the University of Illinois has found the gene for the cod antifreeze protein has come from a non-coding region of their DNA sometimes referred to as 'junk DNA'.</cite>" http://www.sebiology.org.uk/Publications/pageview.asp?S=7&mid=&id=554</ref>. * Some junk DNA could be spacer material that allows [[enzyme]] complexes to form around functional elements more easily. In this way, the junk DNA could serve an important function even though the actual sequence information it contains is irrelevant. * Some portions of junk DNA could serve presently unknown regulatory functions, controlling the expression of certain genes during the development of an organism from [[embryo]] to adult<ref>{{cite journal | author=Woolfe, A., ''et al.'' | title=Highly conserved non-coding sequences are associated with vertebrate development | journal=PLoS Biol | year=2005 | pages=e7 | volume=3 | issue=1 | pmid=15630479 {{doi|10.1371/journal.pbio.0030007}} | doi=10.1371/journal.pbio.0030007}}</ref>, and/or development of certain organs/organelles<ref name=Pellionisz>{{cite web| author=Simons and Pellionisz| title=Genomics, morphogenesis and biophysics: Triangulation of Purkinje cell development| url=http://www.junkdna.com/fractogene/05_simons_pellionisz.html| year=2006}}</ref>. * Regulatory layers in some "junk DNA", such as through [[non-coding RNA]]s, may contain important genetic programming.<ref>[http://www.imb.uq.edu.au/index.html?page=11681&pid=11669 Institute for Molecular Bioscience, RNA-Based Gene Regulation in Mammalian Development - John Mattick<!-- Bot generated title -->]</ref> ==Evolutionary conservation of junk DNA== [[Comparative genomics]] is a promising direction in studying the function of junk DNA. Biologically functional sequences tend to undergo mutation at a slower rate than nonfunctional sequence, since mutations in these sequences are likely to be [[natural selection|selected against]]. For example, the coding sequence of a human protein-coding gene is typically about 80% identical to its mouse [[ortholog]], while their genomes as a whole are much more widely diverged. Analyzing the patterns of conservation between the genomes of different species can suggest which sequences are functional, or at least which functional sequences are shared by those species. Functional elements stand out in such analyses as having diverged less than the surrounding sequence. Comparative studies of several mammalian genomes suggest that approximately 5% of the human genome has evolved under [[Stabilizing selection|purifying selection]]<ref name=Mouse>{{ cite journal | author=Mouse Genome Sequencing Consortium | title=Initial sequencing and comparative analysis of the mouse genome | journal=Nature | volume=420 | pages=520-562 | date=December [[2002]] | doi=10.1038/nature01262 | issue=6915 }}</ref> since their divergence. Since known functional sequence comprises less than 2% of the human genome, there may be more junk DNA in the human genome than there is functional sequence. A surprising recent finding was the discovery of nearly 500 ''ultraconserved'' elements<ref name=Bejerano> G. Bejerano et al. "[http://www.soe.ucsc.edu/%7Ejill/ultra.html Ultraconserved Elements in the Human Genome]". ''Science'' '''304''':1321-1325, May [[2004]]. Discussed in "[http://www.nature.com/nsu/040503/040503-9.html 'Junk' DNA reveals vital role]", ''[[Nature (journal)|Nature]]'' (2004). </ref>, which are shared at extraordinarily high fidelity among the available vertebrate genomes, in what had previously been designated as junk DNA. The function of these sequences is currently under intense scrutiny, and there are preliminary indications<ref name=Bejerano /><ref name=Woolfe>{{ cite journal | author=Woolfe, A., ''et al.'' | title=Highly conserved non-coding sequences are associated with vertebrate development | journal=PLoS Biol | year=2005 | pages=e7 | volume=3 | issue=1 | pmid=15630479 {{doi|10.1371/journal.pbio.0030007}} }}</ref><ref name=Sandelin>{{ cite journal | author=Sandelin, A., ''et al.'' | title=Arrays of ultraconserved elements span the loci of key development genes in vertebrate genomes | journal=BMC Genomics | volume=5 | issue=1 | pages=99 |date=December 2004}} </ref> that some may play a regulatory role in vertebrate development from embryo to adult. Present results concerning evolutionarily conserved human junk DNA are expressed in preliminary, probabilistic terms, since only a handful of related genomes are available. As more vertebrate, and especially mammalian, genomes are sequenced, scientists will develop a clearer picture of this important class of sequence. However, it is always possible, though highly unlikely, that there are significant quantities of functional human DNA that are not shared among these species, and which would thus not be revealed by these studies. Conversely, there are some questions about the hypothesis that conserved sequences all must function <ref name="Nobrega"/>. Replication of junk DNA each time a cell divides may waste energy. Organisms with less junk DNA may therefore have a selective advantage, and [[natural selection]] would tend to eliminate it. There are several possible explanations for why it has not been eliminated: (1) The energy required to replicate even large amounts of junk DNA may be relatively insignificant on the cellular or organismal scale, so no selective pressure results (selection coefficients less than one over the population size are effectively neutral); (2) Junk DNA may provide a reservoir of potentially useful sequences or a protective buffer against harmful genetic damage or mutations; and (3) Junk DNA may accumulate faster than natural selection can eliminate it. In animals, the energy required for DNA synthesis is trivial compared to the metabolic energy invested in the movement of muscles.<ref name=Lodish> {{cite book | last = Lodish | first = Harvey ''et al.'' | title = Molecular Cell Biology | publisher = W. H. Freeman; Sixth Edition | year = 2007 | isbn = 0716776014}}</ref> ==Functions for Some Subsets of Junk DNA== {{Totally-disputed-section|date=July 2008}} {{Cleanup-laundry|date=April 2008}} {{Remove-section|date=July 2008}} * A 2002 study from the University of Michigan showed that segments of junk DNA called LINE-1 elements, once thought to be "leftovers from the distant evolutionary past" now "deserve more respect" because they are capable of repairing broken strands of DNA. <ref>{{cite press release | title = Parasite or partner? Study suggests new role for junk DNA | publisher = Nature Genetics | date = 2002-05-12 | url = http://www.eurekalert.org/pub_releases/2002-05/uomh-pop051002.php | accessdate = 2007-10-14 }}</ref> * A 2003 study from Tel Aviv University found crucial uses for "junk" sequences in human DNA. [http://www.genomenewsnetwork.org/articles/05_03/junk.shtml] * A 2004 study from the Cell Press suggests that "more than one third of the mouse and human genomes, previously thought to be non-functional, may play some role in the regulation of gene expression and promotion of genetic diversity." [http://www.eurekalert.org/pub_releases/2004-10/cp-dm100604.php] * An article from BioEd Online details DNA which appears crucial although no function has yet been discovered. [http://www.bioedonline.org/news/news.cfm?art=956%20] * A 2005 study from the National Institutes of Health found that social behavior in rodents (and, possibly humans [http://www.eurekalert.org/pub_releases/2005-06/euhs-jds060605.php]) was affected by portions of the genetic code once thought to be "junk." [http://www.eurekalert.org/pub_releases/2005-06/niom-rsb060805.php] * A 2005 study from University of California-San Diego suggested that junk DNA is "critically important to an organism’s evolutionary survival." [http://ucsdnews.ucsd.edu/newsrel/science/mcjunk.asp] * Findings from Purdue University in 2005 stated that "many DNA sequences previously believed to have no function actually may play specialized roles in cell behavior." [http://news.uns.purdue.edu/html4ever/2005/050218.Golden.intron.html] * A 2006 study by the McKusick-Nathans Institute of Genetic Medicine (Johns Hopkins) stated that "Junk DNA may not be so junky after all." [http://www.eurekalert.org/pub_releases/2006-03/jhmi-jdm032306.php] * Researchers at the University of Illinois Society for Experimental Biology found an antifreeze-protein gene in a species of fish which appears to have evolved from junk DNA. [http://www.eurekalert.org/pub_releases/2006-04/sfeb-esc033106.php] * A mathematical analysis of the genetic code by IBM identified patterns that suggested junk DNA had an important role after all. [http://news.bbc.co.uk/2/hi/science/nature/4940654.stm] * In 2006, University of Iowa researchers documented segments of [[RNA]] (previously considered "junk") that regulated protein production, and could generate [[microRNA]]s. [http://www.eurekalert.org/pub_releases/2006-11/uoi-uis111306.php] * A 2007 study from Stanford University School of Medicine found that "Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections."<sup>[http://www.eurekalert.org/pub_releases/2007-04/sumc-dn041907.php]</sup> == See also == *[[Atavism]] *[[Alu repeat]] *[[Eukaryotic chromosome fine structure]] *[[Function (biology)]] *[[Genealogical DNA test]] *[[Intron]] *[[Repeated sequence (DNA)]] *[[Retrotransposon]] *[[Satellite DNA]] *[[Selfish DNA]] ==References== {{reflist|2}} ===Further reading=== * Gibbs W.W. ([[2003]]) "The unseen genome: gems among the junk", ''[[Scientific American]]'', '''289'''(5): 46-53. (A review, written for non-specialists, of recent discoveries of function within junk DNA.) [[Category:DNA]] [[Category:Genomics]] [[Category:Mobile genetic elements]] [[ca:ADN escombraries]] [[da:Junk-dna]] [[de:Nichtkodierende Desoxyribonukleinsäure]] [[fr:ADN poubelle]] [[id:DNA sampah]] [[it:DNA non codificante]] [[hu:Repetitív DNS]] [[nl:Junk-DNA]] [[ja:ジャンクDNA]] [[sv:Skräp-DNA]] [[zh:非編碼DNA]]