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==== Biochemical activity ====
Detectable biochemical activity (e.g. [[Transcription (biology)|transcription]], [[Transcription factor-binding site|transcription factor association]], [[chromatin structure]], and [[histone modification]]) was observed for at least 80% of human genomic DNA by the Encyclopedia of DNA Elements ([[ENCODE]]) project.<ref name="Nature489p57">{{cite journal | vauthors = Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, etal | collaboration = The ENCODE Project Consortium | title = An integrated encyclopedia of DNA elements in the human genome | journal = Nature | volume = 489 | issue = 7414 | pages = 57–74 | date = September 2012 | pmid = 22955616 | pmc = 3439153 | doi = 10.1038/nature11247 | bibcode = 2012Natur.489...57T }}.</ref> This forms an upper estimate of the functional portion of the human genome since biochemical activity is not necessarily [[biological function]] or [[Natural selection|selective advantage]].<ref name="observer">{{cite news |url=https://www.theguardian.com/science/2013/feb/24/scientists-attacked-over-junk-dna-claim |title=Scientists attacked over claim that 'junk DNA' is vital to life | vauthors = McKie R |work=The Observer|date=24 February 2013 }}</ref><ref name="eddy">{{cite journal | vauthors = Eddy SR | title = The C-value paradox, junk DNA and ENCODE | journal = Current Biology | volume = 22 | issue = 21 | pages = R898–R899 | date = November 2012 | pmid = 23137679 | doi = 10.1016/j.cub.2012.10.002 | s2cid = 28289437 | author-link = Sean Eddy | doi-access = free }}</ref><ref name="doolittle2013">{{cite journal | vauthors = Doolittle WF | title = Is junk DNA bunk? A critique of ENCODE | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 14 | pages = 5294–5300 | date = April 2013 | pmid = 23479647 | pmc = 3619371 | doi = 10.1073/pnas.1221376110 | author-link = W. Ford Doolittle | bibcode = 2013PNAS..110.5294D | doi-access = free }}</ref><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 }}</ref><ref name="graur">{{cite journal | vauthors = Graur D, Zheng Y, Price N, Azevedo RB, Zufall RA, Elhaik E | title = On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE | journal = Genome Biology and Evolution | volume = 5 | issue = 3 | pages = 578–590 | year = 2013 | pmid = 23431001 | pmc = 3622293 | doi = 10.1093/gbe/evt028 }}</ref> For example, transcription factor binding sites are short and can be found by chance over the whole genome<ref>{{cite journal | vauthors = Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, Chen X, Taipale J, Hughes TR, Weirauch MT | display-authors = 6 | title = The Human Transcription Factors | journal = Cell | volume = 172 | issue = 4 | pages = 650–665 | date = February 2018 | pmid = 29425488 | doi = 10.1016/j.cell.2018.01.029 | s2cid = 3599827 | doi-access = free }}</ref> and 70% of transcribed sequences are below 1 transcript per cell<ref name="kellis" /> and so may be spurious background transcription.<ref name="kellis" />
==== Genetic function ====
Contributing to the debate is that there is no consensus on what constitutes a "functional" element in the genome since geneticists, evolutionary biologists, and molecular biologists employ different approaches and definitions of "function",<ref name="kellis" /> often with a lack of clarity of what they mean in the literature.<ref>{{cite journal |last1=Linquist |first1=Stefan |last2=Doolittle |first2=W. Ford |last3=Palazzo |first3=Alexander F. |title=Getting clear about the F-word in genomics |journal=PLOS Genetics |date=1 April 2020 |volume=16 |issue=4 |pages=e1008702 |doi=10.1371/journal.pgen.1008702|pmid=32236092 |pmc=7153884 }}</ref> Due to the ambiguity in the terminology, there are different schools of thought over this matter.<ref>{{cite journal |last1=Doolittle |first1=W. Ford |title=We simply cannot go on being so vague about 'function' |journal=Genome Biology |date=December 2018 |volume=19 |issue=1 |pages=223 |doi=10.1186/s13059-018-1600-4|pmid=30563541 |pmc=6299606 |doi-access=free }}</ref>
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