Editing Intron (section)

== Biological functions and evolution ==
While introns do not encode protein products, they are integral to gene expression regulation. Some introns themselves encode functional RNAs through further processing after splicing to generate [[noncoding RNA]] molecules.<ref>{{cite journal | vauthors = Rearick D, Prakash A, McSweeny A, Shepard SS, Fedorova L, Fedorov A | title = Critical association of ncRNA with introns | journal = Nucleic Acids Research | volume = 39 | issue = 6 | pages = 2357–2366 | date = March 2011 | pmid = 21071396 | pmc = 3064772 | doi = 10.1093/nar/gkq1080 }}</ref> [[Alternative splicing]] is widely used to generate multiple proteins from a single gene. Furthermore, some introns play essential roles in a wide range of gene expression regulatory functions such as [[nonsense-mediated decay]]<ref>{{cite journal | vauthors = Bicknell AA, Cenik C, Chua HN, Roth FP, Moore MJ | title = Introns in UTRs: why we should stop ignoring them | journal = BioEssays | volume = 34 | issue = 12 | pages = 1025–1034 | date = December 2012 | pmid = 23108796 | doi = 10.1002/bies.201200073 | s2cid = 5808466 | doi-access = free }}</ref> and mRNA export.<ref name="Cenik2011">{{cite journal | vauthors = Cenik C, Chua HN, Zhang H, Tarnawsky SP, Akef A, Derti A, Tasan M, Moore MJ, Palazzo AF, Roth FP | display-authors = 6 | title = Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes | journal = PLOS Genetics | volume = 7 | issue = 4 | pages = e1001366 | date = April 2011 | pmid = 21533221 | pmc = 3077370 | doi = 10.1371/journal.pgen.1001366 | veditors = Snyder M | doi-access = free }}</ref>

After the initial discovery of introns in protein-coding genes of the eukaryotic nucleus, there was significant debate as to whether introns in modern-day organisms were inherited from a common ancient ancestor (termed the introns-early hypothesis), or whether they appeared in genes rather recently in the evolutionary process (termed the introns-late hypothesis). Another theory is that the [[spliceosome]] and the intron-exon structure of genes is a relic of the [[RNA world]] (the introns-first hypothesis).<ref>{{cite journal | vauthors = Penny D, Hoeppner MP, Poole AM, Jeffares DC | title = An overview of the introns-first theory | journal = Journal of Molecular Evolution | volume = 69 | issue = 5 | pages = 527–540 | date = November 2009 | pmid = 19777149 | doi = 10.1007/s00239-009-9279-5 | s2cid = 22386774 | bibcode = 2009JMolE..69..527P }}</ref> There is still considerable debate about the extent to which of these hypotheses is most correct but the popular consensus at the moment is that following the formation of the first eukaryotic cell group II introns from the bacterial endosymbiont invaded the host genome. In the beginning these self-splicing introns excised themselves from the mRNA precursor but over time some of them lost that ability and their excision had to be aided in ''trans'' by other group II introns. Eventually a number of specific trans-acting introns evolved and these became the precursors to the [[snRNA]]s of the spliceosome. The efficiency of splicing was improved by association with stabilizing proteins to form the primitive spliceosome.<ref>{{ cite journal | vauthors = Cavalier-Smith T | title = Intron phylogeny: a new hypothesis | date = 1991 | journal = Trends in Genetics | volume = 7 | issue = 5 | pages = 145–148 | doi = 10.1016/0168-9525(91)90377-3 | pmid = 2068786 }}</ref><ref>{{ cite journal | vauthors = Doolittle WF | title = The origins of introns | date = 1991 | journal = Current Biology | volume = 1 | issue = 3 | pages = 145–146 | doi = 10.1016/0960-9822(91)90214-h | pmid = 15336149 | bibcode = 1991CBio....1..145D | s2cid = 35790897 }}</ref><ref>{{ cite journal | vauthors = Sharp PA | date = 1991 | title = "Five easy pieces."(role of RNA catalysis in cellular processes) | journal = Science | volume = 254 | issue = 5032 | pages = 663–664 | doi = 10.1126/science.1948046 | pmid = 1948046 | s2cid = 508870 }}</ref><ref>{{ cite journal | vauthors = Irimia M, and Roy SW | date = 2014 | title = Origin of spliceosomal introns and alternative splicing. | journal = Cold Spring Harbor Perspectives in Biology | volume = 6 | issue = 6 | pages = a016071 | doi = 10.1101/cshperspect.a016071| pmid = 24890509 | pmc = 4031966 }}</ref>

Early studies of genomic DNA sequences from a wide range of organisms show that the intron-exon structure of homologous genes in different organisms can vary widely.<ref>{{cite journal | vauthors = Rodríguez-Trelles F, Tarrío R, Ayala FJ | title = Origins and evolution of spliceosomal introns | journal = Annual Review of Genetics | volume = 40 | pages = 47–76 | year = 2006 | pmid = 17094737 | doi = 10.1146/annurev.genet.40.110405.090625 }}</ref> More recent studies of entire [[eukaryote|eukaryotic]] [[genome]]s have now shown that the lengths and density (introns/gene) of introns varies considerably between related species. For example, while the human genome contains an average of 8.4 introns/gene (139,418 in the genome), the unicellular fungus ''[[Encephalitozoon cuniculi]]'' contains only 0.0075 introns/gene (15 introns in the genome).<ref>{{cite journal | vauthors = Mourier T, Jeffares DC | title = Eukaryotic intron loss | journal = Science | volume = 300 | issue = 5624 | pages = 1393 | date = May 2003 | pmid = 12775832 | doi = 10.1126/science.1080559 | s2cid = 7235937 }}</ref> Since eukaryotes arose from a common ancestor ([[common descent]]), there must have been extensive gain or loss of introns during evolutionary time.<ref>{{cite journal | vauthors = Roy SW, Gilbert W | title = The evolution of spliceosomal introns: patterns, puzzles and progress | journal = Nature Reviews. Genetics | volume = 7 | issue = 3 | pages = 211–221 | date = March 2006 | pmid = 16485020 | doi = 10.1038/nrg1807 | s2cid = 33672491 }}</ref><ref>{{cite journal | vauthors = de Souza SJ | title = The emergence of a synthetic theory of intron evolution | journal = Genetica | volume = 118 | issue = 2–3 | pages = 117–121 | date = July 2003 | pmid = 12868602 | doi = 10.1023/A:1024193323397 | s2cid = 7539892 }}</ref> This process is thought to be subject to selection, with a tendency towards intron gain in larger species due to their smaller population sizes, and the converse in smaller (particularly unicellular) species.<ref>{{cite journal | vauthors = Lynch M | title = Intron evolution as a population-genetic process | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 9 | pages = 6118–6123 | date = April 2002 | pmid = 11983904 | pmc = 122912 | doi = 10.1073/pnas.092595699 | doi-access = free | bibcode = 2002PNAS...99.6118L }}</ref> Biological factors also influence which genes in a genome lose or accumulate introns.<ref>{{cite journal | vauthors = Jeffares DC, Mourier T, Penny D | title = The biology of intron gain and loss | journal = Trends in Genetics | volume = 22 | issue = 1 | pages = 16–22 | date = January 2006 | pmid = 16290250 | doi = 10.1016/j.tig.2005.10.006 }}</ref><ref>{{cite journal | vauthors = Jeffares DC, Penkett CJ, Bähler J | title = Rapidly regulated genes are intron poor | journal = Trends in Genetics | volume = 24 | issue = 8 | pages = 375–378 | date = August 2008 | pmid = 18586348 | doi = 10.1016/j.tig.2008.05.006 }}</ref><ref>{{cite journal | vauthors = Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA | title = Selection for short introns in highly expressed genes | journal = Nature Genetics | volume = 31 | issue = 4 | pages = 415–418 | date = August 2002 | pmid = 12134150 | doi = 10.1038/ng940 | s2cid = 9057609 | url = https://zenodo.org/record/1233421 }}</ref>

[[Alternative splicing]] of exons within a gene after intron excision acts to introduce greater variability of protein sequences translated from a single gene, allowing multiple related proteins to be generated from a single gene and a single precursor mRNA transcript. The control of alternative RNA splicing is performed by a complex network of signaling molecules that respond to a wide range of intracellular and extracellular signals.

Introns contain several short sequences that are important for efficient splicing, such as acceptor and donor sites at either end of the intron as well as a branch point site, which are required for proper splicing by the [[spliceosome]]. Some introns are known to enhance the expression of the gene that they are contained in by a process known as [[Intron Mediated Enhancement|intron-mediated enhancement]] (IME).

Actively transcribed regions of [[DNA]] frequently form [[R-loop]]s that are vulnerable to [[DNA damage (naturally occurring)|DNA damage]]. In highly expressed yeast genes, introns inhibit R-loop formation and the occurrence of DNA damage.<ref name="pmid28757210">{{cite journal | vauthors = Bonnet A, Grosso AR, Elkaoutari A, Coleno E, Presle A, Sridhara SC, Janbon G, Géli V, de Almeida SF, Palancade B | display-authors = 6 | title = Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability | journal = Molecular Cell | volume = 67 | issue = 4 | pages = 608–621.e6 | date = August 2017 | pmid = 28757210 | doi = 10.1016/j.molcel.2017.07.002 | doi-access = free }}</ref> Genome-wide analysis in both yeast and humans revealed that intron-containing genes have decreased R-loop levels and decreased DNA damage compared to intronless genes of similar expression.<ref name="pmid28757210" /> Insertion of an intron within an R-loop prone gene can also suppress R-loop formation and [[genetic recombination|recombination]]. Bonnet et al. (2017)<ref name="pmid28757210" /> speculated that the function of introns in maintaining genetic stability may explain their evolutionary maintenance at certain locations, particularly in highly expressed genes.

=== Starvation adaptation ===
The physical presence of introns promotes cellular resistance to starvation via intron enhanced repression of ribosomal protein genes of nutrient-sensing pathways.<ref>{{cite journal | vauthors = Parenteau J, Maignon L, Berthoumieux M, Catala M, Gagnon V, Abou Elela S | title = Introns are mediators of cell response to starvation | journal = Nature | volume = 565 | issue = 7741 | pages = 612–617 | date = January 2019 | pmid = 30651641 | doi = 10.1038/s41586-018-0859-7 | s2cid = 58014466 | bibcode = 2019Natur.565..612P }}</ref>