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http://dx.doi.org/10.5808/GI.2015.13.4.112

Introns: The Functional Benefits of Introns in Genomes  

Jo, Bong-Seok (Department of Medical Biotechnology, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University)
Choi, Sun Shim (Department of Medical Biotechnology, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University)
Publication Information
Genomics & Informatics / v.13, no.4, 2015 , pp. 112-118 More about this Journal
Abstract
The intron has been a big biological mystery since it was first discovered in several aspects. First, all of the completely sequenced eukaryotes harbor introns in the genomic structure, whereas no prokaryotes identified so far carry introns. Second, the amount of total introns varies in different species. Third, the length and number of introns vary in different genes, even within the same species genome. Fourth, all introns are copied into RNAs by transcription and DNAs by replication processes, but intron sequences do not participate in protein-coding sequences. The existence of introns in the genome should be a burden to some cells, because cells have to consume a great deal of energy to copy and excise them exactly at the correct positions with the help of complicated spliceosomal machineries. The existence throughout the long evolutionary history is explained, only if selective advantages of carrying introns are assumed to be given to cells to overcome the negative effect of introns. In that regard, we summarize previous research about the functional roles or benefits of introns. Additionally, several other studies strongly suggesting that introns should not be junk will be introduced.
Keywords
first intron; functional roles of introns; introns; selective advantage;
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1 Martin W, Koonin EV. Introns and the origin of nucleus-cytosol compartmentalization. Nature 2006;440:41-45.   DOI
2 Koonin EV. Intron-dominated genomes of early ancestors of eukaryotes. J Hered 2009;100:618-623.   DOI
3 Rogozin IB, Wolf YI, Sorokin AV, Mirkin BG, Koonin EV. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 2003;13:1512-1517.   DOI
4 Sakharkar MK, Chow VT, Kangueane P. Distributions of exons and introns in the human genome. In Silico Biol 2004;4: 387-393.
5 Lynch M. The Origins of Genome Architecture. Sunderland: Sinauer Associates, 2007.
6 Lynch M. Intron evolution as a population-genetic process. Proc Natl Acad Sci U S A 2002;99:6118-6123.   DOI
7 Blake CC. Do genes-in-pieces imply proteins-in-pieces? Nature 1978;273:267.   DOI
8 Blake C. Exons: present from the beginning? Nature 1983; 306:535-537.   DOI
9 Blake CC. Exons and the evolution of proteins. Int Rev Cytol 1985;93:149-185.   DOI
10 Gilbert W. Why genes in pieces? Nature 1978;271:501.   DOI
11 Gilbert W. Genes-in-pieces revisited. Science 1985;228:823-824.   DOI
12 Gruss P, Lai CJ, Dhar R, Khoury G. Splicing as a requirement for biogenesis of functional 16S mRNA of simian virus 40. Proc Natl Acad Sci U S A 1979;76:4317-4321.   DOI
13 Cavaller-Smith T. The Evolution of Genome Size. Chichester: John Wiley & Sons Ltd., 1985.
14 Doolittle RF. The genealogy of some recently evolved vertebrate proteins. Trends Biochem Sci 1985;10:233-237.
15 Rogers J. Exon shuffling and intron insertion in serine protease genes. Nature 1985;315:458-459.   DOI
16 Sudhof TC, Goldstein JL, Brown MS, Russell DW. The LDL receptor gene: a mosaic of exons shared with different proteins. Science 1985;228:815-822.   DOI
17 Cech TR, Bass BL. Biological catalysis by RNA. Annu Rev Biochem 1986;55:599-629.   DOI
18 Li W, Graur D. Fundamentals of Molecular Evolution. Sunderland: Sinauer Associates, 1991.
19 Wen-Hsiung L. Molecular Evolution. Sunderland: Sinauer Associates Inc., 1997.
20 Jareborg N, Birney E, Durbin R. Comparative analysis of noncoding regions of 77 orthologous mouse and human gene pairs. Genome Res 1999;9:815-824.   DOI
21 Shabalina SA, Kondrashov AS. Pattern of selective constraint in C. elegans and C. briggsae genomes. Genet Res 1999;74:23-30.   DOI
22 Bergman CM, Kreitman M. Analysis of conserved noncoding DNA in Drosophila reveals similar constraints in intergenic and intronic sequences. Genome Res 2001;11:1335-1345.   DOI
23 Sorek R, Ast G. Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Res 2003;13:1631-1637.   DOI
24 Beaulieu E, Green L, Elsby L, Alourfi Z, Morand EF, Ray DW, et al. Identification of a novel cell type-specific intronic enhancer of macrophage migration inhibitory factor (MIF) and its regulation by mithramycin. Clin Exp Immunol 2011;163: 178-188.   DOI
25 Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008;40:1413-1415.   DOI
26 Roy M, Kim N, Xing Y, Lee C. The effect of intron length on exon creation ratios during the evolution of mammalian genomes. RNA 2008;14:2261-2273.   DOI
27 Callis J, Fromm M, Walbot V. Introns increase gene expression in cultured maize cells. Genes Dev 1987;1:1183-1200.   DOI
28 Valencia P, Dias AP, Reed R. Splicing promotes rapid and efficient mRNA export in mammalian cells. Proc Natl Acad Sci U S A 2008;105:3386-3391.   DOI
29 Schwartz S, Meshorer E, Ast G. Chromatin organization marks exon-intron structure. Nat Struct Mol Biol 2009;16: 990-995.   DOI
30 Spies N, Nielsen CB, Padgett RA, Burge CB. Biased chromatin signatures around polyadenylation sites and exons. Mol Cell 2009;36:245-254.   DOI
31 Lewis BP, Green RE, Brenner SE. Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci U S A 2003; 100:189-192.   DOI
32 Hillman RT, Green RE, Brenner SE. An unappreciated role for RNA surveillance. Genome Biol 2004;5:R8.   DOI
33 Park SG, Hannenhalli S, Choi SS. Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals. BMC Genomics 2014;15:526.   DOI
34 Kalyna M, Simpson CG, Syed NH, Lewandowska D, Marquez Y, Kusenda B, et al. Alternative splicing and nonsense-mediated decay modulate expression of important regulatory genes in Arabidopsis. Nucleic Acids Res 2012;40: 2454-2469.   DOI
35 Marais G, Nouvellet P, Keightley PD, Charlesworth B. Intron size and exon evolution in Drosophila. Genetics 2005;170: 481-485.   DOI
36 Bradnam KR, Korf I. Longer first introns are a general property of eukaryotic gene structure. PLoS One 2008;3:e3093.   DOI
37 Otto SP, Barton NH. The evolution of recombination: removing the limits to natural selection. Genetics 1997;147:879-906.
38 Comeron JM, Williford A, Kliman RM. The Hill-Robertson effect: evolutionary consequences of weak selection and linkage in finite populations. Heredity (Edinb) 2008;100:19-31.   DOI
39 Carvunis AR, Rolland T, Wapinski I, Calderwood MA, Yildirim MA, Simonis N, et al. Proto-genes and de novo gene birth. Nature 2012;487:370-374.   DOI
40 Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 2014;42:D1001-D1006.   DOI
41 Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 2005;11:241-247.   DOI
42 Buchman AR, Berg P. Comparison of intron-dependent and intron- independent gene expression. Mol Cell Biol 1988;8:4395-4405.   DOI
43 Dieci G, Preti M, Montanini B. Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics 2009;94:83-88.   DOI
44 Rearick D, Prakash A, McSweeny A, Shepard SS, Fedorova L, Fedorov A. Critical association of ncRNA with introns. Nucleic Acids Res 2011;39:2357-2366.   DOI
45 ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74.   DOI
46 Clark AJ, Archibald AL, McClenaghan M, Simons JP, Wallace R, Whitelaw CB. Enhancing the efficiency of transgene expression. Philos Trans R Soc Lond B Biol Sci 1993;339:225-232.   DOI
47 Juneau K, Miranda M, Hillenmeyer ME, Nislow C, Davis RW. Introns regulate RNA and protein abundance in yeast. Genetics 2006;174:511-518.   DOI
48 Shabalina SA, Ogurtsov AY, Spiridonov AN, Novichkov PS, Spiridonov NA, Koonin EV. Distinct patterns of expression and evolution of intronless and intron-containing mammalian genes. Mol Biol Evol 2010;27:1745-1749.   DOI
49 Oswald A, Oates AC. Control of endogenous gene expression timing by introns. Genome Biol 2011;12:107.   DOI
50 Parra G, Bradnam K, Rose AB, Korf I. Comparative and functional analysis of intron-mediated enhancement signals reveals conserved features among plants. Nucleic Acids Res 2011;39:5328-5337.   DOI
51 Luo MJ, Reed R. Splicing is required for rapid and efficient mRNA export in metazoans. Proc Natl Acad Sci U S A 1999; 96:14937-14942.   DOI
52 Tourmente S, Chapel S, Dreau D, Drake ME, Bruhat A, Couderc JL, et al. Enhancer and silencer elements within the first intron mediate the transcriptional regulation of the beta 3 tubulin gene by 20-hydroxyecdysone in Drosophila Kc cells. Insect Biochem Mol Biol 1993;23:137-143.   DOI
53 Green RE, Lewis BP, Hillman RT, Blanchette M, Lareau LF, Garnett AT, et al. Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease genes. Bioinformatics 2003;19 Suppl 1:i118-i121.   DOI
54 Ryu WS, Mertz JE. Simian virus 40 late transcripts lacking excisable intervening sequences are defective in both stability in the nucleus and transport to the cytoplasm. J Virol 1989; 63:4386-4394.
55 Rodrigues JP, Rode M, Gatfield D, Blencowe BJ, Carmo-Fonseca M, Izaurralde E. REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus. Proc Natl Acad Sci U S A 2001;98:1030-1035.   DOI
56 Nott A, Meislin SH, Moore MJ. A quantitative analysis of intron effects on mammalian gene expression. RNA 2003;9: 607-617.   DOI
57 Palazzo AF, Springer M, Shibata Y, Lee CS, Dias AP, Rapoport TA. The signal sequence coding region promotes nuclear export of mRNA. PLoS Biol 2007;5:e322.   DOI
58 Majewski J, Ott J. Distribution and characterization of regulatory elements in the human genome. Genome Res 2002;12: 1827-1836.   DOI
59 Haddrill PR, Charlesworth B, Halligan DL, Andolfatto P. Patterns of intron sequence evolution in Drosophila are dependent upon length and GC content. Genome Biol 2005;6:R67.   DOI
60 Hong X, Scofield DG, Lynch M. Intron size, abundance, and distribution within untranslated regions of genes. Mol Biol Evol 2006;23:2392-2404.   DOI
61 Antoniou M, Geraghty F, Hurst J, Grosveld F. Efficient 3'-end formation of human beta-globin mRNA in vivo requires sequences within the last intron but occurs independently of the splicing reaction. Nucleic Acids Res 1998;26:721-729.   DOI
62 Hachet O, Ephrussi A. Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization. Nature 2004;428:959-963.   DOI
63 Matsumoto K, Wassarman KM, Wolffe AP. Nuclear history of a pre-mRNA determines the translational activity of cytoplasmic mRNA. EMBO J 1998;17:2107-2121.   DOI
64 Furger A, O'Sullivan JM, Binnie A, Lee BA, Proudfoot NJ. Promoter proximal splice sites enhance transcription. Genes Dev 2002;16:2792-2799.   DOI
65 Li MJ, Wang P, Liu X, Lim EL, Wang Z, Yeager M, et al. GWASdb: a database for human genetic variants identified by genome-wide association studies. Nucleic Acids Res 2012;40: D1047-D1054.   DOI
66 Hawkins JD. A survey on intron and exon lengths. Nucleic Acids Res 1988;16:9893-9908.   DOI
67 Deutsch M, Long M. Intron-exon structures of eukaryotic model organisms. Nucleic Acids Res 1999;27:3219-3228.   DOI
68 Simpson AG, MacQuarrie EK, Roger AJ. Eukaryotic evolution: early origin of canonical introns. Nature 2002;419:270.   DOI
69 Jeffares DC, Mourier T, Penny D. The biology of intron gain and loss. Trends Genet 2006;22:16-22.   DOI
70 Mourier T, Jeffares DC. Eukaryotic intron loss. Science 2003;300:1393.   DOI
71 Koonin EV. The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate? Biol Direct 2006;1:22.   DOI
72 Wahl MC, Will CL, Luhrmann R. The spliceosome: design principles of a dynamic RNP machine. Cell 2009;136:701-718.   DOI
73 Chorev M, Carmel L. The function of introns. Front Genet 2012;3:55.