Non-coding DNA: Difference between revisions

Revision as of 12:52, 18 August 2023

Revision as of 05:31, 24 August 2023

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Introns are the parts of a gene that are transcribed into the [[precursor RNA]] sequence, but ultimately removed by [[RNA splicing]] during the processing to mature RNA. Introns are found in both types of genes: protein-coding genes and noncoding genes. They are present in prokaryotes but they are much more common in eukaryotic genomes.{{citation needed|date=June 2022}}

Group I and group II introns take up only a small percentage of the genome when they are present. Spliceosomal introns (see Figure) are only found in eukaryotes and they can represent a substantial proportion of the genome. In humans, for example, introns in protein-coding genes cover 37% of the genome. Combining that with about 1% coding sequences means that protein-coding genes occupy about 38% of the human genome. The calculations for noncoding genes are more complicated because there's considerable dispute over the total number of noncoding genes but taking only the well-defined examples means that noncoding genes occupy at least 6% of the genome.<ref>{{ cite journal | vauthors = Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S | date = 2012 | title = GENCODE: the reference human genome annotation for The ENCODE Project | journal = Genome Research | volume = 22 | issue = 9 | pages = 1760–1774 | doi = 10.1101/gr.135350.111| pmid = 22955987 | pmc = 3431492 }}</ref><ref name = Piovesan>{{ cite journal | vauthors = Piovesan A, Antonaros F, Vitale L, Strippoli P, Pelleri MC, Caracausi M | date = 2019 | title = Human protein-coding genes and gene feature statistics in 2019 | journal = BMC Research Notes | volume = 12 | issue = 1 | pages = 315 | doi = 10.1186/s13104-019-4343-8| pmid = 31164174 | pmc = 6549324 | doi-access = free }}</ref>

===Untranslated regions===

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DNA synthesis begins at specific sites called [[Origin of replication|origins of replication]]. These are regions of the genome where the DNA replication machinery is assembled and the DNA is unwound to begin DNA synthesis. In most cases, replication proceeds in both directions from the replication origin.

The main features of replication origins are sequences where specific initiation proteins are bound. A typical replication origin covers about 100-200 base pairs of DNA. Prokaryotes have one origin of replication per chromosome or plasmid but there are usually multiple origins in eukaryotic chromosomes. The human genome contains about 100,000 origins of replication representing about 0.3% of the genome.<ref>{{cite journal |vauthors=Leonard AC, Méchali M |title=DNA replication origins |journal=Cold Spring Harbor Perspectives in Biology |volume=5 |pages=a010116 |date=2013 |issue=10 |doi=10.1101/cshperspect.a010116|pmid=23838439 |pmc=3783049 }}</ref><ref>{{cite journal |vauthors=Urban JM, Foulk MS, Casella C, Gerbi SA |date=2015 |title=The hunt for origins of DNA replication in multicellular eukaryotes |journal=F1000Prime Reports |volume=7 |page=30 |doi=10.12703/P7-30|pmid=25926981 |pmc=4371235 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Prioleau M, MacAlpine DM |date=2016 |title=DNA replication origins—where do we begin? |journal=Genes & Development |volume=30 |issue=15 |pages=1683–1697 |doi=10.1101/gad.285114.116|pmid=27542827 |pmc=5002974 }}</ref>

===Centromeres===

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===Junk DNA===

{{Main|Junk DNA}}

Junk DNA is DNA that has no biologically relevant function such as pseudogenes and fragments of once active transposons. Bacteria and viral genomes have very little junk DNA<ref>{{cite journal | vauthors = Gil R, and Latorre A | date = 2012 | title = Factors behind junk DNA in bacteria | journal = Genes | volume = 3 | issue = 4 | pages = 634–650 | doi = 10.3390/genes3040634 | pmid = 24705080 | pmc = 3899985 | doi-access = free }}</ref><ref>{{Cite journal |last1=Brandes |first1=Nadav |last2=Linial |first2=Michal |date=2016 |title=Gene overlapping and size constraints in the viral world |journal=Biology Direct |language=en |volume=11 |issue=1 |pages=26 |doi=10.1186/s13062-016-0128-3 |pmid=27209091 |pmc=4875738 |issn=1745-6150 |doi-access=free }}</ref> but some eukaryotic genomes may have a substantial amount of junk DNA.<ref name="PalazzoGregory2014">{{cite journal | vauthors = Palazzo AF, Gregory TR | title = The case for junk DNA | journal = PLOS Genetics | volume = 10 | issue = 5 | pages = e1004351 | date = May 2014 | pmid = 24809441 | pmc = 4014423 | doi = 10.1371/journal.pgen.1004351 | doi-access = free }}</ref> The exact amount of nonfunctional DNA in humans and other species with large genomes has not been determined and there is considerable controversy in the scientific literature.<ref>{{cite journal | last = Morange | first = Michel | date = 2014 | title = Genome as a Multipurpose Structure Built by Evolution | journal = Perspectives in Biology and Medicine | volume = 57 | issue = 1 | pages = 162–171 | doi = 10.1353/pbm.2014.0008 | pmid = 25345709 | s2cid = 27613442 | url = https://hal.archives-ouvertes.fr/hal-01480552/file/ARTICLE%20ENCODE%20MM%2070114%20corrige%C2%A6%C3%BC.pdf }}</ref><ref>{{cite journal | vauthors = Haerty W, and Ponting CP | title = No Gene in the Genome Makes Sense Except in the Light of Evolution. | year = 2014 | journal = Annual Review of Genomics and Human Genetics | volume =25 | pages = 71–92 | doi = 10.1146/annurev-genom-090413-025621| pmid = 24773316 }}</ref>

The nonfunctional DNA in bacterial genomes is mostly located in the intergenic fraction of non-coding DNA but in eukaryotic genomes it may also be found within [[introns]]. It's important to note that there are many examples of functional DNA elements in non-coding DNA (see above) and there are no scientists who claim that all non-coding DNA is junk.

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==Genome-wide association studies (GWAS) and non-coding DNA==

[[Genome-wide association studies]] (GWAS) identify linkages between alleles and observable traits such as phenotypes and diseases. Most of the associations are between [[single-nucleotide polymorphisms]] (SNPs) and the trait being examined and most of these SNPs are located in non-functional DNA. The association establishes a linkage that helps map the DNA region responsible for the trait but it doesn't necessarily identify the mutations causing the disease or phenotypic difference.<ref>{{ cite journal | vauthors = Korte A, Farlwo A | date = 2013 | title = The advantages and limitations of trait analysis with GWAS: a review | journal = Plant Methods | volume = 9 | pages = 29 | doi = 10.1186/1746-4811-9-29| pmid = 23876160 | pmc = 3750305 | s2cid = 206976469 | doi-access = free }}</ref><ref name = Manolio>{{cite journal | vauthors = Manolio TA | title = Genomewide association studies and assessment of the risk of disease | journal = The New England Journal of Medicine | volume = 363 | issue = 2 | pages = 166–76 | date = July 2010 | pmid = 20647212 | doi = 10.1056/NEJMra0905980 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Visscher PV, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, Yang J | date = 2017 | title = 10 Years of GWAS Discovery: Biology, Function, and Translation | journal = American Journal of Human Genetics | volume = 101 | issue = 1 | pages = 5–22 | doi = 10.1016/j.ajhg.2017.06.005| pmid = 28686856 | pmc = 5501872 }}</ref><ref>{{ cite journal | vauthors = Gallagher MD, Chen-Plotkin, AS | date = 2018 | title = The Post-GWAS Era: From Association to Function | journal = American Journal of Human Genetics | volume = 102 | issue = 5 | pages = 717–730 | doi = 10.1016/j.ajhg.2018.04.002| pmid = 29727686 | pmc = 5986732 }}</ref><ref>{{ cite journal | vauthors = Marigorta UM, Rodríguez JA, Gibson G, Navarro A | date = 2018 | title = Replicability and Prediction: Lessons and Challenges from GWAS | journal = Trends in Genetics | volume = 34 | issue = 7 | pages = 504–517 | doi = 10.1016/j.tig.2018.03.005| pmid = 29716745 | pmc = 6003860 }}</ref>

SNPs that are tightly linked to traits are the ones most likely to identify a causal mutation. (The association is referred to as tight [[linkage disequilibrium]].) About 12% of these polymorphisms are found in coding regions; about 40% are located in introns; and most of the rest are found in intergenic regions, including regulatory sequences.<ref name=Manolio/>

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* {{cite book | vauthors = Bennett MD, Leitch IJ | year = 2005 | chapter = Genome size evolution in plants |chapter-url=https://books.google.com/books?id=8HtPZP9VSiMC&pg=PA89 | title = The Evolution of the Genome | veditors = Gregory RT | publisher = Elsevier | ___location = San Diego | pages = 89–162 |isbn=978-0-08-047052-8}}

* {{cite book |doi=10.1016/B978-012301463-4/50003-6 |chapter=Genome Size Evolution in Animals |title=The Evolution of the Genome |year=2005 | vauthors = Gregory TR |pages=3–87 |isbn=978-0-12-301463-4 }}

* {{cite journal | vauthors = Shabalina SA, Spiridonov NA | title = The mammalian transcriptome and the function of non-coding DNA sequences | journal = Genome Biology | volume = 5 | issue = 4 | pages = 105 | year = 2004 | pmid = 15059247 | pmc = 395773 | doi = 10.1186/gb-2004-5-4-105 | doi-access = free }}

* {{cite journal | vauthors = Castillo-Davis CI | title = The evolution of noncoding DNA: how much junk, how much func? | journal = Trends in Genetics | volume = 21 | issue = 10 | pages = 533–536 | date = October 2005 | pmid = 16098630 | doi = 10.1016/j.tig.2005.08.001 }}

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