Although many non-coding regions have biological function,<ref name="Costa non-coding3">{{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="Nessa3">{{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> some portion of non-coding DNA has also 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="PalazzoGregory2014PalazzoGregory20142">{{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 "junk DNA" was used in the 1960s.<ref name="EhretdeHaller1963PalazzoGregory20142" /><ref name="EhretdeHaller19632">{{cite journal |vauthors=Ehret CF, De Haller G |date=October title1963 |title=Origin, development, and maturation of organelles and organelle systems of the cell surface in Paramecium |journal=Journal of Ultrastructure Research |volume=23 |pages=SUPPL6:1–SUPPL642 | date = October 1963 | pmid = 14073743 | doi=10.1016/S0022-5320(63)80088-X |pmid=14073743}}</ref><ref name="PalazzoGregory2014" /><ref name="Gregory Evolution GenomeGenome2">{{cite book| veditors = TR|title=The Evolution of the Genome|date=2005|publisher=Elsevier |isbn=978-0-12-301463-4|pages=29–31|url=https://books.google.com/books?id=8HtPZP9VSiMC&dq=not+only+is+%22junk+dna%22+an+inappropriate+moniker&pg=PA30 |title=The Evolution of the Genome |date=2005 |publisher=Elsevier |isbn=978-0-12-301463-4 |veditors=TR |pages=29–31}}</ref> but it only became widely known in 1972 in a paper by [[Susumu Ohno]].<ref name="OhnoOhno2">{{cite journal |last1=Ohno |first1=S |date=1972 |title=So much 'junk' DNA in our genome |journal=Brookhaven Symposia in Biology |volume=23 |pages=366–70 |oclc=101819442 |pmid=5065367}}</ref> Ohno noted that the [[mutational load]] from deleterious mutations placed an upper limit on the number of functional [[Locus (genetics)|loci]] that could be expected given a typical mutation rate. He hypothesized that mammalian genomes could not have more than 30,000 loci under selection before the "cost" from the mutational load would cause an inescapable decline in fitness, and eventually extinction.<ref name="Ohno2" /> Similar calculations focusing on nucleotides rather than gene loci come to the similar conclusion that the functional portion of the human genome (given mutation rates, genome size and population size) can only be maintained up to approximately 15%.<ref>{{cite journal |last1=Graur |first1=D |year=2017 |title=An Upper Limit on the Functional Fraction of the Human Genome |journal=Genome Biol. Evol. |volume=9 |pages=1880–1885 |doi=10.1093/gbe/evx121 |pmc=5570035 |pmid=28854598 |number=7}}</ref> The presence of junk DNA also explained the observation that even closely related species can have widely (orders-of-magnitude) different genome sizes ([[C-value|C-value paradox]]).<ref name=eddy"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 |doi-access=free |s2cid=28289437}}</ref>
Some authors assert that the term "junk DNA" occurs mainly in [[popular science]] and is no longer used in serious research articles.<ref name="SA2">{{cite journal |vauthors=Khajavinia A, Makalowski W |date=May 2007 |title=What is "junk" DNA, and what is it worth? |journal=Scientific American |volume=296 |issue=5 |pages=104 |bibcode= |doi=10.1038/scientificamerican0507-104 |pmid=17503549 |quote=The term "junk DNA" repelled mainstream researchers from studying noncoding genetic material for many years}}</ref> However, examination of ''Web of Science'' shows immediately that this is at best an oversimplification. For example, given the average deleterious mutation rate and population size, the functional portion of the human genome an only be maintained up to approximately 15%.<ref>{{cite journal