A research programme is said to be progressing as long as its theoretical growth anticipates its empirical growth, that is, as long as it keeps predicting novel facts with some success...; it is stagnating if its theoretical growth lags behind its empirical growth, that is, as long as it gives only post hoc explanations of either chance discoveries or of facts anticipated by, and discovered in, a rival programme.... Imre Lakatos, 1978. (1)
Introns: a Mystery
A surprising phenomenon was discovered in 1977 — introns. These are sequences of DNA, within genes, which have no apparent purpose. The genes containing them were called "split genes." You could think of introns as long commercials, in a language you don't understand, interrupting your favorite television show right in the middle of the action. Introns are rare within prokaryotic cells. They are rare within the nuclear genomes of single-celled eukaryotes. However, within the cells of multicelled animals and plants almost every gene has introns.
If genes evolved this way, then each exon, or minigene, would code for a unit of protein that had some integrity by itself. We know that proteins have identifiable subunits or domains. Until recently, biologists thought that each exon did code for a separate protein domain. Now we know this is not always the case; the exons don't always map to those domains. The breaks between them, the introns, sometimes occur in the middle of a domain (5). Sometimes the breaks even occur within a single codon, the three-nucleotide specifier for a single amino acid. This interruption is analogous to a television commercial between the syllables of a single word. This fact is especially damaging to the exon theory of genes, because any minigenes that started in the middle of a codon would be ruined by frameshift error.
Of course, Cosmic Ancestry does not claim to have the complete explanation for introns either. But it does suggest new ways to approach them. Introns make more sense if evolution is a constructive process requiring the assembly of blocks of instructions imported from outside the cell. Perhaps a gene can be imported whole, but must be disassembled and reassembled elsewhere within the genome by the processes of transposition and site-specific recombination. The fragmented aspect of genes with introns is reminiscent of the way computer code may become physically fragmented after it has been retrieved from the hard drive and returned.
Many genes are very similar from the lowest to the highest eukaryotic animals. Often the main difference among the different creatures' versions of the same gene is that they contain more introns as you go up the evolutionary hierarchy of organization. For quite a few genes, the version possessed by lower eukaryotes such as yeast has no introns, while the versions in more highly organized creatures such as humans have five to fifty. Intermediate species will have intermediate numbers of introns in that gene (9). The number of introns could be related to the number of times a gene has been transferred across a species boundary during evolution.
In 1995, a group of scientists at Ohio State found that some introns possess a capability called "homing." These introns can insert themselves into intronless versions of the genes that normally carry them, at the exact same position they would normally occupy in the version that has introns (10). This happens by a surprising mechanism — the RNA transcript of the intron is spliced directly into the DNA gene. Then by reverse transcription, the DNA complement of the RNA is manufactured and added to the opposite DNA strand (11). The phenomenon of homing by introns is not yet explained by any theory. But it makes sense, if the precise insertion of introns is part of the process whereby new genes are installed. As the scientists at Ohio State innocently comment, "...introns... may well be the key to determining where new information is transferred into a gene."
Additional work in 1998 by a team including some of the same biochemists and molecular biologists strengthens the possibility that introns might play an active part in evolution. They experimented with a mobile group II intron of the bacterial species Lactotottus lactis, which exhibits "retrohoming" capability. They found that these introns are capable of carrying and installing "lengthy foreign sequences without compromising their catalytic activity or mobility." They suggest that the intron might be adapted for use in genetic engineering, to insert "foreign sequences into a variety of eukaryotes" (12)!
Some introns appear to have "slipped" to a slightly different position in closely related genes found in different species. Under Cosmic Ancestry it would be conceivable for an intron to be originally inserted in different positions in different lineages, after two versions of a gene had already diverged from each other slightly. This suggestion gains support from a study published in September 1997 showing that actual slipping of position (or "sliding," "drift," "migration," etc.) cannot account for most examples of the slightly different intron positions (13).
Another study analyzes the distribution of intron phases within the flanking codons of genes. The authors make much of the fact that the exonic sequences around the intron are poorly conserved, and conclude that the data do not support the "introns late" theory (14). But, for example, once an intron has been inserted, its corresponding exonic "homing" sequences might no longer be maintained by selective pressure, a possibility not considered in this study.
One intriguing recent finding is that DNA that contains introns exhibits structure at a very large scale. "A specific nucleotide at one site in a DNA strand appears to have a bearing on ...a specific site 100, 1000, 10,000 or even more nucleotides away" (15). As one of the researchers who made the finding said, "This work raises more questions than it answers."
Occasionally introns do assume a function within the cell — as templates not for RNA that codes for protein but for RNA that has another role. In addition, occasionally, the exons in such a gene are silent (16). This situation is backwards. No one has any idea how this arrangement could have evolved, if strands of nucleotides gradually acquire programming by the neo-darwinian method.
Cosmic Ancestry offers a promising new perspective on the puzzle of introns.
"Genome surveillance by HUSH-mediated silencing of intronless mobile elements" by Marta Seczynska ey al., doi:10.1038/s41586-021-04228-1, Nature, 20 Jan 2022.
Intron retention: importance, challenges, and opportunities by Justin J.-L. Wong and Ulf Schmitz, doi:10.1016/j.tig.2022.03.017, Trends in Genetics, 21 Apr 2022.
Intron-mediated induction of phenotypic heterogeneity by M. Lukačišin, A. Espinosa-Cantú, and T. Bollenbach, doi:10.1038/s41586-022-04633-0, Nature, 20 Apr 2022.
Walking the LINEs hidden in the dark matter of the genome by Marina Lusic and Musa M. Mhlanga, doi:10.1038/s41588-021-01003-w, Nature Genetics, 20 Jan 2022. ...LINE1-containing transcripts are key regulators of T cell effector function and exhaustion. ...often located in introns.
20 Dec 2021: Chimeric RNAs become human genes?!
31 Aug 2021: A newly analysed gene-editing system in an unusual eukaryotic reproductive system.
Massive colonization of protein-coding exons by selfish genetic elements... by Diamantis Sellis, Frédéric Guérin et al., doi:10.1371/journal.pbio.3001309, PLoS Biol, 29 Jul 2021. Similar to the evolution of introns in eukaryotes, the evolution of Paramecium IESs highlights the major role played by selfish genetic elements in shaping the complexity of genome architecture and gene expression.
Is there any intron sliding in mammals? by Irina V. Poverennaya et al., doi:10.1186/s12862-020-01726-0, BMC Evol Biol, 11 Dec 2020. We assume that intron sliding is indeed a very rare evolutionary event if it exists at all. Every case of intron sliding needs a lot of supportive data for detection and confirmation.
Anything but Ordinary – Emerging Splicing Mechanisms in Eukaryotic Gene Regulation by Niels H. Gehring and Jean-Yves Roignant, doi:10.1016/j.tig.2020.10.008, Trends in Genetics, 14 Nov 2020.
Introns: Good Day Junk Is Bad Day Treasure by Julie Parenteau and Sherif Abou Elela, doi:10.1016/j.tig.2019.09.010, Trends in Genetics, 25 Oct 2019.
Evolution of intron splicing towards optimized gene expression is based on various Cis- and Trans-molecular mechanisms by Idan Frumkin et al., PLoS Biol, 23 Aug 2019. Splicing expands, reshapes, and regulates the transcriptome of eukaryotic organisms.
Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome by Jason Talkish et al. doi:10.1371/journal.pgen.1008249, PLoS Genet., 22 Aug 2019.
Satellite DNA-containing gigantic introns in a unique gene expression program during Drosophila spermatogenesis by Jaclyn M. Fingerhut et al.; and commentary: Taming the giant within by Jack R. Bateman and David J. Anderson, PLoS Genet., 09 May 2019. Why do these giant introns exist in the first place?
18 Apr 2019: the "grammar" of proteins can be investigated using tools borrowed from linguistics.
Excised linear introns regulate growth in yeast by Jeffrey T. Morgan et al., Nature, 16 Jan 2019.
Introns are mediators of cell response to starvation by Julie Parenteau et al., Nature, 16 Jan 2019.
04 Dec 2018: Nonhomologous end-joining and retroelements may have played a previously unappreciated role in the evolution of advanced life.
Bacterial group II introns generate genetic diversity by circularization and trans-splicing from a population of intron-invaded mRNAs by Félix LaRoche-Johnston, et al., PLoS Genet., 21 Nov 2018.
Order of removal of conventional and nonconventional introns from nuclear transcripts of Euglena gracilis by Natalia Guminska et al., PLoS Genet., 26 Oct 2018.
Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation by Michael S. Werner et al., doi:10.1101/gr.234872.118, Genome Res., 19 Sep 2018. ...we found a strong bias of C. elegans 1:1 orthologs to be longer and contain more exons than homologs, which in turn were longer and contained more exons than orphan genes.
Origin of exon skipping-rich transcriptomes in animals driven by evolution of gene architecture by Xavier Grau-Bové et al., doi:10.1186/s13059-018-1499-9, Genome Biology, 17 Sep 2018.
Exonic splice regulation imposes strong selection at human synonymous sites by Rosina Savisaar and Laurence D. Hurst, doi:10.1101/gr.233999.117, Genome Res., online 24 Aug 2018.
Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing by Jan Attig, Federico Agostini et al., doi:10.1016/j.cell.2018.07.001, Cell, 23 Aug 2018.
Lariat intronic RNAs in the cytoplasm of vertebrate cells by Gaëlle J. S. Talhouarne and Joseph G. Gall, doi:10.1073/pnas.1808816115, PNAS, online 06 Aug 2018.
19 Oct 2017: panel discussion, W. Ford Doolittle et al., the Library of Congress, 17 Mar 2016.
Environmental perturbations lead to extensive directional shifts in RNA processing by Allison L. Richards et al., PLoS Genet., online 12 Oct 2017. ...we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in alternative first exon (AFE) usage in response to specific treatments.
Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability by Amandine Bonnet et al., doi:10.1016/j.molcel.2017.07.002, Molecular Cell, 17 Aug (online 27 Jul) 2017.
Mobile Group II Introns as Ancestral Eukaryotic Elements by Olga Novikova and Marlene Belfort, doi:10.1016/j.tig.2017.07.009, Trends in Genetics, corrected proof online 20 Aug 2017.
Identification of introns harboring functional sequence elements through positional conservation by Michal Chorev et al., doi:10.1038/s41598-017-04476-0, Scientific Reports, online 23 Jun 2017.
Mobile Introns Shape the Genetic Diversity of Their Host Genes by Jelena Repar and Tobias Warnecke, doi:10.1534/genetics.116.199059, Genetics, online 13 Feb 2017.
Eugene V. Koonin interviewed by Suzan Mazur, Huffington Post, 03 Feb 2017. ...apparently the last common eukaryotic ancestor had an intron density close to that in extant animals.
Mechanism for DNA transposons to generate introns on genomic scales by Jason T. Huff, Daniel Zilberman and Scott W. Roy, doi:10.1038/nature20110, Nature, online 19 Oct 2016. ...two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? by Dror Hollander, Shiran Naftelberg et al., doi:10.1016/j.tig.2016.07.003, Trends in Genetics, Oct 2016.
Impact of a homing intein on recombination frequency and organismal fitness by Adit Naor, Neta Altman-Price et al., doi:10.1073/pnas.1606416113, PNAS, online 26 Jul 2016.
Novel Intronic RNA Structures Contribute to Maintenance of Phenotype in Saccharomyces cerevisiae by Katarzyna B. Hooks, Samina Naseeb et al., doi:10.1534/genetics.115.185363, Genetics, 01 Jul 2016. Overall, these data support the notion that some introns may have been maintained in the genome because they harbor functional RNA structures.
14 Jun 2016: Robust software management systems must effect the assembly, deployment, repair and optimization of acquired genetic programs....
Spliceosomal intronogenesis by Sujin Lee and Scott W. Stevens, doi:10.1073/pnas.1605113113, PNAS, online 23 May 2016. We have experimentally verified, to our knowledge, the first demonstrations of intron transposition in any organism.
Control of neuronal synapse specification by a highly dedicated alternative splicing program by Lisa Traunmüller, Andrea M. Gomez et al., doi:10.1126/science.aaf2397, Science, 12 May 2016.
Splicing of Nascent RNA Coincides with Intron Exit from RNA Polymerase II by Fernando Carrillo Oesterreich, Lydia Herzel et al., doi:10.1016/j.cell.2016.02.045, v 165, Cell, 07 Apr 2016. We show that splicing is 50% complete when Pol II is only 45 nt downstream of introns....
07 Apr 2016: The first molecular-resolution reconstruction of a central assembly of the human spliceosome.
mRNA-Associated Processes and Their Influence on Exon-Intron Structure in Drosophila melanogaster by Gildas Lepennetier and Francesco Catania, doi:10.1534/g3.116.029231, G3, 30 Mar 2016. ...mRNA-associated processes [may] impose significant constraints on the evolution of the eukaryotic gene structure.
The Origins of the RNA World, panel discussion among Walter Gilbert, W. Ford Doolittle, George Fox and Ray Gesteland, 17 Mar 2016: ...the role of introns as a recombination-enhancer to shuffle the exons.... Gilbert.
Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins by Yun-Hua Esther Hsiao et al., doi:10.1101/gr.193359.115, Genome Res., 17 Feb 2016.
Intermediate introns in nuclear genes of euglenids – are they a distinct type? by R Milanowski et al., doi:10.1186/s12862-016-0620-5, BMC Evolutionary Biology, 29 Feb 2016.
24 Feb 2016: ...You have thousands of dead genes scattered throughout your genome, and some of them are just itching to spring back to life. [Book review]
Discovery of RNA splicing and genes in pieces by Arnold J. Berk, doi:10.1073/pnas.1525084113, PNAS, online 19 Jan 2016.
Mitochondrial group I and group II introns in the sponge orders Agelasida and Axinellida by Dorothée Huchon et al., doi:10.1186/s12862-015-0556-1, BMC Evolutionary Biology, 12 Dec 2015. The differences found among intron secondary structures and the phylogenetic inferences support the hypothesis that the introns originated from independent horizontal gene transfer events.
Jing Hang, Ruixue Wan, Chuangye Yan, Yigong Shi, "Structural basis of pre-mRNA splicing," doi:10.1126/science.aac8159, Science, online 20 Aug 2015.
Is nature mostly a tinkerer or an inventor?, PhysOrg.com, 18 Aug 2015.
Heidi Cook-Andersen and Miles F. Wilkinson, "...Splicing does the two-step" [link], doi:10.1038/nature14524, Nature, online 13 May 2015.
...An Interview with Ford Doolittle by Jane Gitschier, PLoS Genet, 7 May 2015.
Yamile Marquez et al., "Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity" [abstract], doi:10.1101/gr.186585.114, Genome Res., online 1 May 2015. "...exitron splicing is a conserved strategy...."
28 Apr 2015: Diversity-generating retroelements (DGRs) use mutagenic reverse transcription and retrohoming to generate myriad variants of a target gene.
Antonia Cianciulli et al., "Determinism and randomness in the evolution of introns and sine inserts in mouse and human mitochondrial solute carrier and cytokine receptor genes" [abstract], doi:10.1016/j.compbiolchem.2015.02.012, p 49-59 v 55, Computational Biology and Chemistry, Apr 2015. "...At higher levels of organization a deterministic component emerges...."
Olga Novikova et al., "Interaction between Conjugative and Retrotransposable Elements in Horizontal Gene Transfer" [html], doi:10.1371/journal.pgen.1004853, PLoS Genetics, 4 Dec 2014.
Ulrich Braunschweig et al., "Widespread intron retention in mammals functionally tunes transcriptomes" [abstract], doi:10.1101/gr.177790.114, p 1774-1786 v 24, Genome Res., Nov 2014.
Tan, Shengjun, Zhu, Zhenglin, Zhu, Tao, Te, Rigen, and Zhang, Yong E, "Chance and Necessity: Emerging Introns in Intronless Retrogenes" [abstract], doi:10.1002/9780470015902.a0022886, eLS, online Aug 2014. "The functional necessity on intron gain in retrogenes remains largely elusive although limited data suggest that newborn introns play regulatory roles, enable exon shuffling and alternative splicing."
Ulrich Braunschweig et al., "Widespread intron retention in mammals functionally tunes transcriptomes" [abstract], doi:10.1101/gr.177790.114, Genome Research, online 25 Sep 2014.
Maxime Bruto et al., "Frequent, independent transfers of a catabolic gene from bacteria to contrasted filamentous eukaryotes" [abstract], doi:10.1098/rspb.2014.0848, n 1789 v 281, Proc. R. Soc. B, 22 Aug (online 2 Jul) 2014. "...Once transferred, this gene acquired introns and was found expressed...."
Mèlanie Meyer et al., "Speciation of a group I intron into a lariat capping ribozyme" [abstract], doi:10.1073/pnas.1322248111, Proc. Natl. Acad. Sci. USA, online 13 May 2014.
W. Ford Doolittle, "The trouble with (group II) introns" [link], doi:0.1073/pnas.1405174111, Proc. Natl. Acad. Sci. USA, online 22 Apr 2014.
B. Franz Lang et al., "Massive programmed translational jumping in mitochondria" [abstract], doi:10.1073/pnas.1322190111, p 5926-5931 v 111, Proc. Natl. Acad. Sci. USA, 22 Apr 2014.
Olga Gorlova et al., "Genes with a large intronic burden show greater evolutionary conservation on the protein level" [abstract], doi:10.1186/1471-2148-14-50, n 50 v 14, BMC Evolutionary Biology, online 16 Mar 2014.
Baojun Wu and Weilong Hao, "Horizontal Transfer and Gene Conversion as an Important Driving Force in Shaping the Landscape of Mitochondrial Introns" [abstract], doi:10.1534/g3.113.009910, G3, online 10 Feb 2014.
Sebastian M. Fica, Nicole Tuttle et al., "RNA catalyses nuclear pre-mRNA splicing" [html], doi:10.1038/nature12734, ...and commentary: Scott A. Strobel, "Biochemistry: Metal ghosts in the splicing machine" [html], doi:10.1038/nature12705, Nature, online 6 Nov 2013.
Aranko AS, Oeemig JS, Kajander T, Iwaï H, "Intermolecular domain swapping induces intein-mediated protein alternative splicing" [abstract], doi:10.1038/nchembio.1320, Nat Chem Biol, online 25 Aug 2013.
Ali R. Awan et al., "Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans" [abstract], doi:10.1073/pnas.1218353110, Proc. Natl. Acad. Sci. USA, online 16 Jul 2013.
Adam Monier et al., "Gene invasion in distant eukaryotic lineages: discovery of mutually exclusive genetic elements reveals marine biodiversity" [abstract], doi:10.1038/ismej.2013.70, ISME Journal, online 2 May 2013.
Jun Yao, David M. Truong and Alan M. Lambowitz, "Genetic and Biochemical Assays Reveal a Key Role for Replication Restart Proteins in Group II Intron Retrohoming" [html], doi:10.1371/journal.pgen.1003469, 9(4): e1003469, PLoS Genet, 25 Apr 2013.
Henan Zhu, Ziwei Zhou, Daxi Wang and Hao Zhu, "Hippo pathway genes developed varied exon numbers and coevolved functional domains in metazoans for species specific growth control" [abstract], doi:10.1186/1471-2148-13-76, n76 v13, BMC Evolutionary Biology, 1 Apr 2013.
Tao Zhu and Deng-Ke Niu, "Frequency of intron loss correlates with processed pseudogene abundance: a novel strategy to test the reverse transcriptase model of intron loss" [abstract], doi:10.1186/1741-7007-11-23, n23 v11, BMC Biology, 5 Mar 2013.
Jean-Luc Da Lage et al., "Gene make-up: rapid and massive intron gains after horizontal transfer of a bacterial alpha-amylase gene to Basidiomycetes" [abstract], doi:10.1186/1471-2148-13-40, n40 v13, BMC Evolutionary Biology, 13 Feb 2013.
Lifang Kang et al., "Newly evolved introns in human retrogenes provide novel insights into their evolutionary roles" [abstract], doi:10.1186/1471-2148-12-128, n128 v12, BMC Evolutionary Biology, online 28 Jul 2012.
Verena Salman et al., "Multiple self-splicing introns in the 16S rRNA genes of giant sulfur bacteria" [Open Access abstract], doi:10.1073/pnas.112019210, Proc. Natl. Acad. Sci. USA, online 27 Feb 2012.
Travis B. White and Alan M. Lambowitz, "The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4-Dependent and -Independent Mechanisms" [html], doi:10.1371/journal.pgen.1002534, e1002534, 8(2), PLoS Genet., online 16 Feb 2012.
Ignacio Maeso et al., "An ancient genomic regulatory block conserved across bilaterians and its dismantling in tetrapods by retrogene replacement" [abstract], doi:10.1101/gr.132233.111, Genome Research, online 10 Jan 2012.
Guixia Xu, Chunce Guo et al., "Divergence of duplicate genes in exon-intron structure" [abstract], doi:10.1073/pnas.1109047109, Proc. Natl. Acad. Sci. USA, online 9 Jan 2012.
Paul Yenerall et al., "Mechanisms of intron gain and loss in Drosophila" [abstract], doi:10.1186/1471-2148-11-364, v11 n364, BMC Evolutionary Biology, online 19 Dec 2011.
Sahar Gelfman et al., "Changes in exon-intron structure during vertebrate evolution affect the splicing pattern of exons" [abstract], doi:10.1101/gr.119834.110, p35-50 v22, Genome Res., Jan 2012 (online 5 Oct 2011.)
Adi Barzel et al., "Home and Away- The Evolutionary Dynamics of Homing Endonucleases" [abstract], doi:10.1186/1471-2148-11-324, v11 n324, BMC Evolutionary Biology, online 4 Nov 2011.
Maria V Sanchez-Puerta et al., "Multiple recent horizontal transfers of the cox1 intron in Solanaceae and extended co-conversion of flanking exons" [abstract], doi:10.1186/1471-2148-11-277, v11 n277, BMC Evolutionary Biology, online 27 Sep 2011.
Giuseppe D. Tocchini-Valentini et al., "Evolution of introns in the archaeal world" [abstract], doi:10.1073/pnas.1100862108, Proc. Natl. Acad. Sci. USA, online 7 Mar 2011.
Ashley Farlow et al., "DNA double-strand break repair and the evolution of intron density" [abstract], doi:10.1016/j.tig.2010.10.004, p1-6 v27, Trends in Genetics, 23 Nov 2010; and a News Release, University of Veterinary Medicine Vienna, [n.d.]
Quinn M. Mitrovich, Brian B. Tuch et al., "Evolution of Yeast Noncoding RNAs Reveals an Alternative Mechanism for Widespread Intron Loss" [abstract], doi:10.1126/science.1194554, p838-841 v330, Science, 5 Nov 2010.
Amir Szitenberg et al., "Diversity of sponge mitochondrial introns revealed by cox 1 sequences of Tetillidae" [abstract], doi:10.1186/1471-2148-10-288, v10 n288, BMC Evolutionary Biology, 20 Sep 2010. "Our results suggest that three different intron forms independently colonized the cox 1 gene of tetillids."
Mari Kawaguchi et al., "Intron-loss evolution of hatching enzyme genes in Teleostei" [abstract], doi:10.1186/1471-2148-10-260, v10 n260, BMC Evolutionary Biology, 27 Jan 2010. "We propose that the high-expression hatching enzyme genes frequently lost their introns during the evolution of teleosts, while the low-expression genes maintained the exon-intron structure of the ancestral gene."
23 Jul 2010: The cell, and indeed evolution, can dial up these microRNAs very flexibly in different cells to address various targets, and they only need one protein complex to come and do the job.
Anna Henricson et al., "Orthology confers intron position conservation" [abstract], doi:10.1186/1471-2164-11-412, BMC Genomics, 2 Jul 2010.
Spying on a cellular director in the cutting room, University of Michigan (also EurekAlert and Newswise), 21 Mar 2010.
Ashley Farlow, Eshwar Meduri et al., "Nonsense-Mediated Decay Enables Intron Gain in Drosophila" [html], doi:10.1371/journal.pgen.1000819, PLoS Genet 6(1): e1000819, Jan 2010.
Wenli Li, Abraham E. Tucker et al., "Extensive, Recent Intron Gains in Daphnia Populations" [abstract], doi:10.1126/science.1179302, p1260-1263 v 326, Science, 27 Nov 2009; also see commentaries:
Introns: A Mystery Renewed, Indiana University (also Newswise.com), 10 Dec 2009. "The scientists say introns are inserted into the genome far more frequently than current models predict. The scientists also found what appear to be 'hot spots' for intron insertion -- areas of the genome where repeated insertions are more likely to occur. And surprisingly, the vast majority of intron DNA sequences the scientists examined were of unknown origin."
Introns -- nonsense DNA -- may be more important to evolution of genomes than thought, ScienceDaily, 14 Dec 2009.
Xiang Gao and Michael Lynch, "Ubiquitous internal gene duplication and intron creation in eukaryotes" [abstract], doi:10.1073/pnas.0911093106, Proc. Natl. Acad. Sci. USA, online 19 Nov 2009. "...implying that internal gene duplications have been originating and disappearing in these genomes at approximately constant rates for many millions of years"
Dustin C. Hancks, Adam D. Ewing et al., "Exon-trapping mediated by the human retrotransposon SVA" [abstract], doi:10.1101/gr.093153.109, p1983-1991 v19, Genome Research, Nov (online 27 Jul) 2009. "These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species."
Fanglei Zhuang, Marta Mastroianni et al., "Linear group II intron RNAs can retrohome in eukaryotes and may use nonhomologous end-joining for cDNA ligation" [abstract], doi:10.1073/pnas.0910277106, Proc. Natl. Acad. Sci. USA, online 15 Oct 2009. "...and suggest that linear group II intron RNAs might be used for site-specific DNA integration in gene targeting."
17 Sep 2009: The gain and loss of exons has contributed to the evolution of new features.
David M. Rand, "'Why genomes in pieces?' revisited: Sucking lice do their own thing in mtDNA circle game" [extract], doi:10.1101/gr.091132.109, p700-702 v19, Genome Res., May 2009.
Kosuke Fujishima et al., "Tri-split tRNA is a transfer RNA made from 3 transcripts that provides insight into the evolution of fragmented tRNAs in archaea" [abstract], doi:10.1073/pnas.0808246106, p 2683-2687 v 106, Proc. Natl. Acad. Sci. USA, 24 Feb 2009. "This suggests that an evolutionary relationship between intron-containing and split tRNAs exists."
Marc Sultan, Marcel H. Schulz, Hugues Richard et al., "A Global View of Gene Activity and Alternative Splicing by Deep Sequencing of the Human Transcriptome" [abstract], doi:10.1126/science.1160342, p 956-960 v 321, Science, 15 Aug 2008. "...Exon skipping is the most prevalent form of alternative splicing."
Manuel Irimia et al., "Origin of introns by 'intronization' of exonic sequences" [abstract], doi:10.1016/j.tig.2008.05.007, Trends in Genetics, online 1 Jul 2008.
Hameed Khan and John M. Archibald, "Lateral transfer of introns in the cryptophyte plastid genome" [html], doi:10.1093/nar/gkn095, p 3043-3053 v 36, Nucleic Acids Research, May (online 8 Apr) 2008.
Rosa Tarrío, Francisco J. Ayala and Francisco Rodríguez-Trelles, "Alternative splicing: A missing piece in the puzzle of intron gain" [abstract], doi:10.1073/pnas.0802941105, Proc. Natl. Acad. Sci. USA, online 7 May 2008.
Chaolin Zhang et al., "RNA landscape of evolution for optimal exon and intron discrimination" [abstract], doi:10.1073/pnas.0801692105, Proc. Natl. Acad. Sci. USA, online 7 Apr 2008. "Our results suggest that human genes have been optimized for exon and intron discrimination...." Also ...a Fingerprint of Evolution..., Cold Spring Harbor Laboratory, 8 Apr 2008.
24 Feb 2008: An intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates.
Christopher E. Lane et al., "Nucleomorph genome of Hemiselmis andersenii reveals complete intron loss and compaction as a driver of protein structure and function" [abstract], 10.1073/pnas.0707419104, Proc. Natl. Acad. Sci. USA, online 6 Dec 2007.
Joanna L. Parmley et al., "Splicing and the Evolution of Proteins in Mammals" [article], PLoS Biology, online 6 Feb 2007. "Here we test the hypothesis that selection acting to ensure that introns are correctly removed skews amino acid content in predictable ways and imposes constraints on rates of protein evolution."
Degen Zhuo et al., "Modern origin of numerous alternatively spliced human introns from tandem arrays" [abstract], 10.1073/pnas.0604777104, Proc. Natl. Acad. Sci. USA, online 8 Jan 2007.
Jasmin Coulombe-Huntington and Jacek Majewski, "Characterization of intron loss events in mammals" [abstract], 10.1101/gr.5703406, Genome Research, online 15 Nov 2006.
Francisco Rodríguez-Trelles, Rosa Tarrío and Francisco J. Ayala, "Origins and Evolution of Spliceosomal Introns" [abstract], 10.1146/annurev.genet.40.110405.090625, p 47-76 v 40, Annual Review of Genetics, Dec (online 12 Jun) 2006. Introns first?
Scott William Roy and David Penny, "Large-scale intron conservation and order-of-magnitude variation in intron loss/gain rates in apicomplexan evolution" [abstract], 10.1101/gr.5410606, p 1270-1275 v 16, Genome Research, Oct (online 8 Sep) 2006. "We suggest that intron loss/gain in some eukaryotic lineages may be concentrated in relatively short episodes coincident with occasional TE invasions."
The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate? by Eugene V Koonin, doi:10.1186/1745-6150-1-22, Biol. Direct, online 14 Aug 2006.
Scott William Roy, Manuel Irimia and David Penny, "Very Little Intron Gain in Entamoeba histolytica Genes Laterally Transferred from Prokaryotes" [abstract], 10.1093/molbev/msl061, p 1824-1827 v 23, Molecular Biology and Evolution, Oct (online 17 Jul) 2006.
20 June 2006: Bats and horses are closely related, according to a genomic study using retroposon (L1) analysis.
4 May 2006: A gene captured from a mobile element fused with another gene to make a new primate gene. (A newly created intron allowed the fusion.)
18 Feb 2006: Splicesomal introns are found in the nuclear genomes of all characterized eukaryotes.
Linda Bonen and Sophie Calixte, "Comparative Analysis of Bacterial-Origin Genes for Plant Mitochondrial Ribosomal Proteins" [abstract], 10.1093/molbev/msj080, p 701-712 v 23, Molecular Biology and Evolution, Mar 2006 (online 20 Dec 2005). "We find that genes that were transferred to the nucleus early in eukaryotic evolution have, on average, about twofold higher density of introns within the core ribosomal protein sequences than do those that moved to the nucleus more recently. About 20% of such introns are at positions identical to those in human orthologs, consistent with their ancestral presence."
Alexander E. Vinogradov, "'Genome design' model: Evidence from conserved intronic sequence in human-mouse comparison" [abstract], 10.1101/gr.4318206, Genome Research, online 3 Feb 2006."These results suggest that the greater length of introns in tissue-specific genes is ...related to functional complexity...."
Daniel C. Jeffares et al., "The biology of intron gain and loss," 10.1016/j.tig.2005.10.006, Trends in Genetics, online 14 Nov 2005.
25 Nov 2005: A small marine worm has complex genes like humans'.
Giuseppe D. Tocchini-Valentini et al., "Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea" [abstract], 10.1073/pnas.0506750102, Proc. Natl. Acad. Sci. USA, online 12 Oct 2005.
Deng-Ke Niu, Wen-Ru Hou and Shu-Wei Li, "mRNA-Mediated Intron Losses: Evidence from Extraordinarily Large Exons" [abstract], 10.1093/molbev/msi138, p 1475-1481 v 22, Molecular Biology and Evolution, (online 23 Mar) Jun 2005.
Scott William Roy and Walter Gilbert, "Rates of intron loss and gain: Implications for early eukaryotic evolution" [abstract], 10.1073/pnas.0500383102, Proc. Natl. Acad. Sci. USA, online 12 Apr 2005.
Lesley Collins and David Penny, "Complex Spliceosomal Organization Ancestral to Extant Eukaryotes," doi:10.1093/molbev/msi091 [abstract], p 1053-1066 v 22 n 4, Molecular Biology and Evolution, Apr 2005.
Scott William Roy and Walter Gilbert, "Resolution of a deep animal divergence by the pattern of intron conservation" [abstract], 10.1073/pnas.0409891102, Proc. Natl. Acad. Sci. USA, online 15 Mar 2005.
28 Feb 2005: Can pre-existing genetic programs be pieced together?
3 Feb 2005: Complex early genes.
Scott W. Roy and Walter Gilbert, "The pattern of intron loss" [abstract], 10.1073/pnas.0408274102, p 713-718 v 102, Proc. Natl. Acad. Sci. USA, 18 Jan 2005 (online 10 Jan).
Alan M. Lambowitz and Steven Zimmerly, "Mobile Group II Introns" [abstract], p 1-35 v 38, Annual Review of Genetics, Dec 2004.
Scott W. Roy, "The origin of recent introns: transposons?" [abstract], doi: 10.1186/gb-2004-5-12-251, p 251 v 5, Genome Biology, Dec 2004 (online 29 Nov).
John M. Logsdon Jr., "Worm genomes hold the smoking guns of intron gain" [abstract], Proc. Natl. Acad. Sci. USA, online 26 July 2004.
Avril Coghlan and Kenneth H. Wolfe, "Origins of recently gained introns in Caenorhabditis" [abstract, pdf], Proc. Natl. Acad. Sci. USA, online 8 July 2004.
Wei-Gang Qiu, Nick Schisler and Arlin Stoltzfus, "The Evolutionary Gain of Spliceosomal Introns: Sequence and Phase Preferences," p 1252-1263 v 21 n 7 Mol. Biol. Evol., July 2004. "...Intron gain accounts for the vast majority of extant introns...".
Eirik W. Lundblad et al., "Twelve Group I Introns in the Same Pre-rRNA Transcript of the Myxomycete Fuligo septica: RNA Processing and Evolution," p 1283-1293 v 21 n 7 Mol. Biol. Evol., July 2004. "...Most Fuligo introns were distantly related to each other and were independently gained in ribosomal DNA during evolution...".
NIST-led Research De-Mystifies Origins Of 'Junk' DNA SpaceDaily.com, 26 Mar 2004. "Research from the CARB group appears to resolve a debate over the 'early versus late' timing of the appearance of introns."
Kenji Ichiyanagi, Arthur Beauregard and Marlene Belfort, "A bacterial group II intron favors retrotransposition into plasmid targets" [abstract], p 15742-15747 v 100, Proc. Natl. Acad. Sci. USA, online 12 Dec, print 23 Dec 2003.
Camilla L. Nesbø and W. Ford Doolittle, "Active self-splicing group I introns in 23S rRNA genes of hyperthermophilic bacteria, derived from introns in eukaryotic organelles" [abstract], p 10806-10811 v 100, Proc. Natl. Acad. Sci. USA, 16 Sep 2003.
2003, June 30: Introns can cause new stretches of DNA to be precisely inserted into genomes.
Scott W. Roy, Alexei Fedorov and Walter Gilbert, "Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain" [abstract], p 7158-7162 v 100 n 12 Proc. Natl. Acad. Sci. USA, 10 Jun 2003.
Tobias Mourier and Daniel C. Jeffares, "Eukaryotic Intron Loss" [text], p 1393 v 300, Science, 30 May 2003. "...There must have been considerable gain of introns in some lineages, intron loss in others, or a combination of both processes."
Rosa Tarrío, Francisco Rodríguez-Trelles and Francisco J. Ayala, "A new Drosophila spliceosomal intron position is common in plants" [abstract], p 6580-6583 n 11 v 100, Proc. Natl. Acad. Sci. USA, 15 May 2003. "The extremely disjointed phylogenetic distribution of the intron argues strongly for separate gain rather than recurrent loss."
Scott William Roy, Alexei Fedorov, and Walter Gilbert, "The signal of ancient introns is obscured by intron density and homolog number" [abstract], p 15513-15517 n 24 v 99, Proc. Natl. Acad. Sci. USA, 26 Nov 2002.
Ana Llopart et al., "Intron presence-absence polymorphism in Drosophila driven by positive Darwinian selection" [abstract], p 8121-8126 v 99 n 12, Proc. Natl. Acad. Sci. USA, 11 June 2002. "Population genetic analyses ...indicate the action of positive Darwinian selection on the intron-absent variant."
Michael Lynch, "Intron evolution as a population-genetic process" [abstract], p 6118-6123 v 99 n 9 Proc. Natl. Acad. Sci. USA, 30 April 2002. Convincing support for "introns-late" without accounting for the origin of introns.
Ancient Protozoan [has an intron] by Elizabeth Pennisi, Daily inScight, 25 Feb 2002.
Lorna Dickson et al., "Retrotransposition of a yeast group II intron occurs by reverse splicing directly into ectopic DNA sites" [abstract], p 13207-13212 v 98 n 23 Proc. Natl. Acad. Sci. USA, 6 November 2001.
2001, March 14: Intronless paralogs...
2000, July 20: Introns' homing capability may become useful in genetic engineering.
Major Player Found That Clips Introns From RNA by Peta Gillyatt, UniSci, 11 November 1999.
1998, November 30: Biologists find evidence that a certain intron underwent cross-species horizontal transfer over 1,000 times during angiosperm evolution.
1998, November 3: Two geneticists find evidence for "a predominating integration mechanism," that inserts acquired foreign genes into genomes in clustered fragments.
John M. Logsdon, Jr., "The recent origins of spliceosomal introns revisited," p 637-648 v 8, Current Opinion in Genetics & Development, 1998.
1998, August 25: We owe the repertoire of our immune system to one transposon insertion, which occurred 450 million years ago in the ancestor of the jawed fishes.
1998, August 12: The paradigm shifts toward lateral gene transfer as the primary driver of evolution.
Introns and Exons (>300K text, gifs and jpgs): Reprints of technical papers (1981-2001) and introductory comments by Donald R. Forsdyke, Biochemist, Queen's University, Kingston, Ontario, Canada.
de Souza SJ, Long M, Gilbert W., "Introns and gene evolution" [full text], p 493-505 v 1 n 6 Genes to Cells, Jun 1996.
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