Introns, derived from the term "intragenic regions" and also called "intervening sequence" (IVS) [Cite web
url = http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-I/intron.html
title = intron (intervening sequence)
author = Mark Lefers
publisher = Department of Biochemistry, Molecular Biology, and Cell Biology, Weinberg College of Arts & Sciences, Northwestern University
accessdate = 2008-06-17] , are DNA regions in a
genethat are not translated into proteins. These non-coding sections are present in precursor mRNA(pre-mRNA) and some other RNAs, and removed by a process called splicing during the processing to mature RNA. After intron splicing, the mRNA consists only of exons, which are translated into a protein.
The number and length of introns varies widely among
species, and among genes within the same species. Some eukaryotes, e.g. sac fungi, have evolved genomes with few introns, [cite journal |author=Stajich JE, Dietrich FS, Roy SW |title=Comparative genomic analysis of fungal genomes reveals intron-rich ancestors |journal=Genome Biol. |volume=8 |issue=10 |pages=R223 |year=2007 |pmid=17949488 |pmc=2246297 |doi=10.1186/gb-2007-8-10-r223] while the genomes of many other eukaryote groups are rich in introns (several per gene). [cite journal |author=Csurös M, Rogozin IB, Koonin EV |title=Extremely intron-rich genes in the alveolate ancestors inferred with a flexible maximum-likelihood approach |journal=Mol. Biol. Evol. |volume=25 |issue=5 |pages=903–11 |year=2008 |month=May |pmid=18296415 |doi=10.1093/molbev/msn039 |url=] [cite journal |author=Smith DR, Lee RW |title=Nucleotide diversity in the mitochondrial and nuclear compartments of Chlamydomonas reinhardtii: investigating the origins of genome architecture |journal=BMC Evol. Biol. |volume=8 |issue= |pages=156 |year=2008 |pmid=18495022 |pmc=2412866 |doi=10.1186/1471-2148-8-156] Alternative splicingof introns within a gene may introduce greater variability of protein sequences translated from a single gene. The control of mRNA splicing is performed by a wide variety of signaling molecules.
Introns may also contain "old code", or sections of a gene that were once translated into a protein, but have since become inactive. It was generally assumed that the sequence of any given intron is
junk DNAwith no biological function. More recently, however, this is being disputed. [cite journal |author=Crosio C, Cecconi F, Mariottini P, Cesareni G, Brenner S, Amaldi F |title=Fugu intron oversize reveals the presence of U15 snoRNA coding sequences in some introns of the ribosomal protein S3 gene |journal=Genome Res. |volume=6 |issue=12 | pages = e15 |year=1996 |month=December |pmid=8973918 |url=http://www.genome.org/cgi/pmidlookup?view=long&pmid=8973918 | doi = 10.1101/gr.6.12.1227 ]
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
The discovery of introns led to the
Nobel Prize in Physiology or Medicinein 1993 for Phillip Allen Sharpand Richard J. Roberts. The term "intron" was introduced by American biochemist Walter Gilbert: [cite journal
author=Gilbert, Walter |authorlink=Walter Gilbert |year=1978 |title=Why genes in pieces |journal=Nature |volume=271 |issue=5645 |pages=501 |doi=10.1038/271501a0]
"The notion of the cistron [...] must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger - which I suggest we call introns (for intragenic regions) - alternating with regions which will be expressed - exons." (Gilbert 1978)
Classification of introns
Four classes of introns are known to exist:
*Group I intron
Group II intron
Group III intronSome introns, such as the Group I and Group II introns, after transcription possess ribozymeactivity, enabling them to catalyze their own splicing out of a primary RNA transcript. These introns are thus self splicing introns and are relatively rare compared to spliceosomal introns. This self-splicing activity was discovered by Thomas Cech, who shared the 1989 Nobel Prize in Chemistrywith Sidney Altmanfor the discovery of the catalytic properties of RNA.
Nuclear or spliceosomal introns are spliced by the
spliceosomeand a series of snRNAs (small nuclear RNAs). There are certain splice signals (or consensus sequences) which abet the splicing (or identification) of these introns by the spliceosome.
Group II and III introns are similar and have a conserved
secondary structure. A so-called lariat pathway is used in their splicing. They perform functions similar to the spliceosome and may be evolutionarily related to it. Group I introns are the only class of introns whose splicing requires a free guanine nucleoside. They possess a secondary structuredifferent from that of group II and III introns.Many self-splicing introns code for maturases that help with the splicing process, generally only the splicing of the intron that encodes it. [cite journal |author=Doetsch NA, Thompson MD, Hallick RB |title=A maturase-encoding group III twintron is conserved in deeply rooted euglenoid species: are group III introns the chicken or the egg? |journal=Mol. Biol. Evol. |volume=15 |issue=1 |pages=76–86 |year=1998 |month=January |pmid=9491607 |doi= |url=http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9491607]
There are two competing theories that offer alternative scenarios for the origin and early
evolutionof spliceosomal introns. Other classes of introns such as self-splicing and tRNAintrons are not subject to much debate, but see [ Gogarten JP, Hilario E. "Inteins, introns, and homing endonucleases: recent revelations about the life cycle of parasitic genetic elements." "BMC Evol Biol." 2006 Nov 13; 6: 94. PMID 17101053] for the former. These are popularly called as the Introns-Early (IE) or the Introns-Late (IL) views. [cite journal |author=Roy SW, Gilbert W |title=The evolution of spliceosomal introns: patterns, puzzles and progress |journal=Nat. Rev. Genet. |volume=7 |issue=3 |pages=211–21 |year=2006 |month=March |pmid=16485020 |doi=10.1038/nrg1807 |url=http://www.faculty.biol.ttu.edu/densmore/MB06pdfs/Nat.rev.intron%20evol.pdf]
The "IE model", championed by Walter Gilbert, [Fedorov A, Cao X, Saxonov S, de Souza SJ, Roy SW, Gilbert W. "Intron distribution difference for 276 ancient and 131 modern genes suggests the existence of ancient introns." "Proc Natl Acad Sci U S A." 2001 Nov 6; 98(23): 13177-82. PMID 11687643.] proposes that introns are extremely old and numerously present in the earliest ancestors of
prokaryotesand eukaryotes(the progenote). In this model introns were subsequently lost from prokaryotic organisms, allowing them to attain growth efficiency. A central prediction of this theory is that the early introns were mediators that facilitated the recombination of exons that represented the protein domains. [Rodriguez-Trelles F, Tarrio R, Ayala, FJ. " [http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.genet.40.110405.090625?cookieSet=1 Origins and evolution of spliceosomal introns] ." "Annual Review of Genetics" 2006; 40: 47-76.] This model cannot account for some observed positional variation of introns shared among related genes. [Rzhetsky A, Ayala FJ. " [http://www.springerlink.com/content/lgvc0bly6j5wn3n0/fulltext.pdf The enigma of intron origins] ." "Cellular and Molecular Life Sciences" 1999; 55(1): 3-6.]
The "IL model" proposes that introns were more recently inserted into originally intron-less contiguous genes after the divergence of eukaryotes and prokaryotes. In this model, introns probably originated from
transposable elements. This model is based on the observation that the spliceosomal introns are restricted to eukaryotes alone. However, there is considerable debate over the presence of introns in the early prokaryote-eukaryote ancestors and the subsequent intron loss-gain during eukaryotic evolution. [Sverdlov AV, Csuros M, Rogozin IB, Koonin EV. "A glimpse of a putative pre-intron phase of eukaryotic evolution." "Trends Genet." 2007 Mar; 23(3): 105-108. PMID 17239982] The evolution of introns and of the intron-exon structure may be largely independent of the evolution of coding-sequences. [cite journal |author=Yandell M, Mungall CJ, Smith C, "et al" |title=Large-scale trends in the evolution of gene structures within 11 animal genomes |journal=PLoS Comput. Biol. |volume=2 |issue=3 |pages=e15 |year=2006 |month=March |pmid=16518452 |doi=10.1371/journal.pcbi.0020015]
eukaryoticnuclear introns begin with the nucleotidesequence GU, and end with AG (the GU-AG rule). These, along with a larger consensus sequence, help direct the splicing machinery to the proper intronic donor and acceptor sites.
Eukaryotic gene example
Eukaryotic chromosome fine structureSplicing:
* [http://www.sgn.cornell.edu/tools/intron_detection/find_introns.pl Intron finding tool for plant genomic sequences]
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