Editing Human genome (section)

=== Junk DNA ===
{{Main|Junk DNA}}

There is no consensus on what constitutes a "functional" element in the genome since geneticists, evolutionary biologists, and molecular biologists employ different definitions and methods.<ref name="kellis">{{cite journal | vauthors = Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos JA, Weng Z, White KP, Hardison RC | title = Defining functional DNA elements in the human genome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 17 | pages = 6131–6138 | date = April 2014 | pmid = 24753594 | doi = 10.1073/pnas.1318948111 | pmc = 4035993 | bibcode = 2014PNAS..111.6131K | doi-access = free }}</ref><ref>{{cite journal | vauthors = Linquist S, Doolittle WF, Palazzo AF | title = Getting clear about the F-word in genomics | journal = PLOS Genetics | volume = 16 | issue = 4 | pages = e1008702 | date = April 2020 | pmid = 32236092 | pmc = 7153884 | doi = 10.1371/journal.pgen.1008702 | doi-access = free }}</ref> Due to the ambiguity in the terminology, different schools of thought have emerged.<ref>{{cite journal | vauthors = Doolittle WF | title = We simply cannot go on being so vague about 'function' | journal = Genome Biology | volume = 19 | issue = 1 | pages = 223 | date = December 2018 | pmid = 30563541 | pmc = 6299606 | doi = 10.1186/s13059-018-1600-4 | doi-access = free }}</ref> In evolutionary definitions, "functional" DNA, whether it is coding or non-coding, contributes to the fitness of the organism, and therefore is maintained by negative [[evolutionary pressure]] whereas "non-functional" DNA has no benefit to the organism and therefore is under neutral selective pressure. This type of DNA has been described as [[junk DNA]].<ref name = "Graur_2017">{{cite book | vauthors = Graur D | chapter = Rubbish DNA: the functionless fraction of the human genome. | doi = 10.1007/978-4-431-56603-8_2 | title = Evolution of the Human Genome I | series = Evolutionary Studies | date = 2017 | pages = 19–60 | publisher = Springer | location = Tokyo | arxiv = 1601.06047 | isbn = 978-4-431-56603-8 | s2cid = 17826096 }}</ref><ref name = "Pena_2021">{{cite book | vauthors = Pena SD | chapter = An Overview of the Human Genome: Coding DNA and Non-Coding DNA |veditors = Haddad LA |title=Human Genome Structure, Function and Clinical Considerations |date=2021 |publisher=Springer Nature |location=Cham |isbn=978-3-03-073151-9 |pages=5–7 | chapter-url=https://books.google.com/books?id=cTYyEAAAQBAJ&dq=junk+DNA+controversy&pg=PA5}}</ref> In genetic definitions, "functional" DNA is related to how DNA segments manifest by phenotype and "nonfunctional" is related to loss-of-function effects on the organism.<ref name="kellis" /> In biochemical definitions, "functional" DNA relates to DNA sequences that specify molecular products (e.g. noncoding RNAs) and biochemical activities with mechanistic roles in gene or genome regulation (i.e. DNA sequences that impact cellular level activity such as cell type, condition, and molecular processes).<ref>{{cite journal | vauthors =Abascal F, Acosta R, Addleman NJ, Adrian J, et al. |title=Expanded Encyclopaedias of DNA elements in the Human and Mouse Genomes |journal=Nature |date=30 July 2020 |volume=583 |issue=7818 |pages=699–710 |doi=10.1038/s41586-020-2493-4|pmid=32728249 |pmc=7410828 |bibcode=2020Natur.583..699E | quote= Operationally, functional elements are defined as discrete, linearly ordered sequence features that specify molecular products (for example, protein-coding genes or noncoding RNAs) or biochemical activities with mechanistic roles in gene or genome regulation (for example, transcriptional promoters or enhancers).}}</ref><ref name="kellis" /> There is no consensus in the literature on the amount of functional DNA since, depending on how "function" is understood, ranges have been estimated from up to 90% of the human genome is likely nonfunctional DNA (junk DNA)<ref>{{cite journal | vauthors = Graur D | title = An Upper Limit on the Functional Fraction of the Human Genome | journal = Genome Biology and Evolution | volume = 9 | issue = 7 | pages = 1880–1885 | date = July 2017 | pmid = 28854598 | pmc = 5570035 | doi = 10.1093/gbe/evx121 }}{{lay source |template=cite news | vauthors = Le Page M |url=https://www.newscientist.com/article/2140926-at-least-75-per-cent-of-our-dna-really-is-useless-junk-after-all/ |title=At least 75 per cent of our DNA really is useless junk after all |date= 17 July 2017 |work= NewScientist }}</ref> to up to 80% of the genome is likely functional.<ref name=Nature489p57>{{cite journal | vauthors = Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, et. al | 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 | quote = These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions.}}.</ref> It is also possible that junk DNA may acquire a function in the future and therefore may play a role in evolution,<ref name="pmid16237443">{{cite journal | vauthors = Andolfatto P | title = Adaptive evolution of non-coding DNA in Drosophila | journal = Nature | volume = 437 | issue = 7062 | pages = 1149–52 | date = October 2005 | pmid = 16237443 | doi = 10.1038/nature04107 | bibcode = 2005Natur.437.1149A | s2cid = 191219 }} {{lay source |template=cite news |url=https://www.sciencedaily.com/releases/2005/10/051020090946.htm |title=UCSD Study Shows 'Junk' DNA Has Evolutionary Importance |date= 20 October 2005 |work=ScienceDaily |location=Rockville, MD}}</ref> but this is likely to occur only very rarely.<ref name = "Graur_2017" /> Finally DNA that is deliterious to the organism and is under negative selective pressure is called garbage DNA.<ref name = "Pena_2021" />