In bacteria, the coding regions typically take up 88% of the genome.<ref name=":0" /> The remaining 12% consistsdoes largelynot encode proteins, but much of it still has biological function through genes where the RNA transcript is functional (non-coding genes) and regulatory sequences, which means that almost all of the bacterial genome has a function.<ref name=":0">{{cite journal | vauthors = Kirchberger PC, Schmidt ML, and Ochman H | date = 2020 | title = The ingenuity of bacterial genomes | journal = Annual Review of Microbiology | volume = 74 | pages = 815–834 | doi = 10.1146/annurev-micro-020518-115822| pmid = 32692614 | s2cid = 220699395 }}</ref> The amount of coding DNA in eukaryrotes is usually a much smaller fraction of the genome because eukaryotic genomes contain large amounts of repetitive DNA not found in prokaryotes. The [[human genome]] contains somewhere between 1–2% coding DNA.<ref name = Piovesan/><ref>{{ cite journal | vauthors = Omenn GS | date = 2021 | title = Reflections on the HUPO Human Proteome Project, the Flagship Project of the Human Proteome Organization, at 10 Years | journal = Molecular & Cellular Proteomics | volume = 20 | pages = 100062 | doi = 10.1016/j.mcpro.2021.100062| pmid = 33640492 | pmc = 8058560 }}</ref> The exact number is not known because there are disputes over the number of functional coding exons and over the total size of the human genome. This means that 98–99% of the human genome consists of non-coding DNA and this includes many functional elements such as non-coding genes and regulatory sequences.
[[Genome size]] in eukaryotes can vary over a wide range, even between closely related sequences. This puzzling observation was originally known as the [[C-value | C-value Paradox]] where "C" refers to the haploid genome size.<ref>{{cite journal | vauthors = Thomas CA | title = The genetic organization of chromosomes | journal = Annual Review of Genetics | volume = 5 | pages = 237–256 | date = 1971 | pmid = 16097657 | doi = 10.1146/annurev.ge.05.120171.001321 }}</ref> The paradox was resolved with the discovery that most of the differences were due to the expansion and contraction of repetitive DNA and not the number of genes. Some researchers speculated that this repetitive DNA was mostly junk DNA. The reasons for the changes in genome size are still being worked out and this problem is called the C-value Enigma.<ref>{{ cite journal | vauthors = Elliott TA, Gregory TR | date = 2015 | title = What's in a genome? The C-value enigma and the evolution of eukaryotic genome content | journal = Phil. Trans. R. Soc. B | volume = 370 | issue = 1678 | pages = 20140331 | doi = 10.1098/rstb.2014.0331| pmid = 26323762 | pmc = 4571570 | s2cid = 12095046 }}</ref>
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==Junk DNA==
{{Main|Junk DNA}}
Although many non-coding regions have biological function,<ref name="Costa non-coding32">{{cite book |title=Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection |vauthors=Costa F |date=2012 |publisher=[[Caister Academic Press]] |isbn=978-1-904455-94-3 |veditors=Morris KV |chapter=7 Non-coding RNAs, Epigenomics, and Complexity in Human Cells}}{{page needed|date=June 2022}}</ref><ref name="Nessa32">{{cite book |title=Junk DNA: A Journey Through the Dark Matter of the Genome |vauthors=Carey M |date=2015 |publisher=Columbia University Press |isbn=978-0-231-17084-0 |author-link=Nessa Carey}}{{page needed|date=June 2022}}</ref> much of the non-coding DNA in most genomes does not have biological function and has been described as "Junk DNA". Though exact definitions differ, this refers broadly to "any DNA sequence that does not play a functional role in development, physiology, or some other organism-level capacity."<ref name="PalazzoGregory20142">{{cite journal |vauthors=Palazzo AF, Gregory TR |date=May 2014 |title=The case for junk DNA |journal=PLOS Genetics |volume=10 |issue=5 |pages=e1004351 |doi=10.1371/journal.pgen.1004351 |pmc=4014423 |pmid=24809441}}</ref> The term has been contentious as different definitions of what conostitutesconstitutes biologcalbiological function lead to higlyhighly different estimates of what proportion of a genome falls into the category.<ref name=":02">{{cite journal |last1=Palazzo |first1=A F |last2=Kejiou |first2=N S |year=2022 |title=Non-Darwinian Molecular Biology |journal=Front. Genet. |volume=13 |pages=831068 |doi=10.3389/fgene.2022.831068 |pmc=8888898 |pmid=35251134 |doi-access=free}}</ref><ref name=":13">{{cite journal |vauthors=Ponting CP, Hardison RC |date=November 2011 |title=What fraction of the human genome is functional? |journal=Genome Research |volume=21 |issue=11 |pages=1769–1776 |doi=10.1101/gr.116814.110 |pmc=3205562 |pmid=21875934}}</ref> In particular, the [[ENCODE]] project in the 2000s demonstrated detectable biochemical activity resulting from most parts of the genome ([[Transcription (biology)|transcription to RNA]], [[Transcription factor-binding site|transcription factor binding]], etc).<ref name="eddy2">{{cite journal |author-link=Sean Eddy |vauthors=Eddy SR |date=November 2012 |title=The C-value paradox, junk DNA and ENCODE |journal=Current Biology |volume=22 |issue=21 |pages=R898–R899 |doi=10.1016/j.cub.2012.10.002 |pmid=23137679 |s2cid=28289437 |doi-access=free}}</ref><ref>{{Cite journal |last=Celniker |first=Susan E. |last2=Dillon |first2=Laura A. L. |last3=Gerstein |first3=Mark B. |last4=Gunsalus |first4=Kristin C. |last5=Henikoff |first5=Steven |last6=Karpen |first6=Gary H. |last7=Kellis |first7=Manolis |last8=Lai |first8=Eric C. |last9=Lieb |first9=Jason D. |last10=MacAlpine |first10=David M. |last11=Micklem |first11=Gos |last12=Piano |first12=Fabio |last13=Snyder |first13=Michael |last14=Stein |first14=Lincoln |last15=White |first15=Kevin P. |date=2009-06 |title=Unlocking the secrets of the genome |url=https://www.nature.com/articles/459927a |journal=Nature |language=en |volume=459 |issue=7249 |pages=927–930 |doi=10.1038/459927a |issn=1476-4687 |pmc=PMC2843545 |pmid=19536255}}</ref> However, whether this biochemical activity is promiscuiouspromiscuous activity in a noisy biological system or evolutionarily relevant biological function has been lesssless clear - and consequently, whether that DNA counts as "junk" or not.<ref name=":13" /><ref name="eddy2" /><ref name=":12">{{cite journal |vauthors=Ponting CP, Hardison RC |date=November 2011 |title=What fraction of the human genome is functional? |journal=Genome Research |volume=21 |issue=11 |pages=1769–1776 |doi=10.1101/gr.116814.110 |pmc=3205562 |pmid=21875934}}</ref>
==Genome-wide association studies (GWAS) and non-coding DNA==
