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 (1)
Introns: a Mystery What'sNEW
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.
By 1977 we already knew that eukaryotic genes were long. We knew that the same genes could be located in different places in different members of the same species. We knew that a lot of DNA was silent. But none of these observations led to the prediction of introns; they were a complete surprise. "Surprisingly" is a very common word in genetics research. The Darwinian paradigm makes very few predictions, yet is often surprised.
Introns are interruptions in the text of eukaryotic genes. Every time the genome is replicated, they are replicated right along with it. For Richard Dawkins, introns are an example of pure "selfish DNA," out for its own survival only. But for the survival of any creature whose genes carry them, introns are a problem to solve. Somehow, at some stage, introns have to be removed before the ultimate product of the gene, the protein, can be made without error.
By 1980 biologists had discovered that eukaryotic cells have an elaborate mechanism for doing the necessary editing. First, the whole DNA sequence, with introns, is transcribed into RNA. Then, within the cell nucleus, specialized arrays of enzymes in complexes called spliceosomes locate the introns, snip them out, and splice the RNA back together. It all must happen with absolutely perfect precision. If the cut or splice is one nucleotide out of place, a "frameshift error" would ruin the entire protein. Only after this precise editing does the RNA pass out of the nucleus, to a ribosome, to be translated into protein.
Introns Early? Introns Late?
Darwinists responded to the discovery of introns by guessing that they arose either early or late. The two versions are called the "introns-early" theory and the "introns-late" theory. When scientists discovered that one primordial species, a photosynthetic cyanobacterium named Fischerella, has introns, both camps claimed that the new evidence supported their view (2).
The introns-early theory is also called the exon theory of genes (3). (Exons are the working or expressed segments of genes. Both terms, "introns" and "exons," were coined by Harvard biologist Walter Gilbert in 1978 (4).) Darwinists like the exon theory of genes because it allows for the buildup of genes from smaller pieces. The theory says exons were minigenes. At some stage, such as precellular life, minigenes would have functioned as genes do today. At a later stage in evolution, the minigenes were assembled to make whole genes. Introns were the functionless pieces that held the exons together. All genes were built that way. Bacteria have no introns, and single-celled eukaryotes have very few because they lost them in later evolutionary stages. That's the introns-early theory.
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.
Meanwhile, the introns-late theory also has a hard time explaining the usefulness of introns. One possibility is, "Introns originated to circumvent the problem of the random distribution of stop codons in random primordial sequences" (6). But Nobel prize-winner Renato Dulbecco, for one, says that the introns couldn't have been added late, because there are too many similarities among the introns found in species that diverged too long ago (7). The Darwinian paradigm has not yet led to any consensus about introns. Rather, the debate between the two camps has become heated. This heat is evident in an extended exchange among experts on both sides that was held on the Internet, 5-17 November 1996 (8).
Introns and Cosmic Ancestry
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. (By such reasoning Cosmic Ancestry is more closely aligned with the "introns late" theory.)
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." Such 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 evolve new functions by the darwinian method.
Cosmic Ancestry offers a promising new perspective on the puzzle of introns.
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."
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.
1. Imre Lakatos, "History of science and its rational reconstructions," p 102-138 The Methodology of Scientific Research Programmes: Philosophical Research Papers Volume I, John Worrall and Gregory Currie, eds. The Press Syndicate of the University of Cambridge, 1978. p 112.
2. Marcia Barinaga, "Introns Pop up in New Places - What Does It Mean?" p 1512 v 250 Science, 14 December 1990.
3. Walter Gilbert, "The Exon Theory of Genes," p 901-905 Cold Spring Harbor Symposia on Quantitative Biology, Volume LII: Evolution of Catalytic Function, Cold Spring Harbor Laboratory, 1987.
4. Walter Gilbert, "Why genes in pieces?" p 501 v 271 Nature. 9 February 1978.
5. Arlin Stoltzfus, David F. Spencer, Michael Zuker, John M. Logsdon, Jr. and W. Ford Doolittle, "Testing the Exon Theory of Genes: The Evidence from Protein Structure," p 202-207 v 265 Science, 8 July 1994.
6. Periannan Senapathy, "Introns and the Origin of Protein-Coding Genes," p 1366-1367 v 268 Science, 2 June 1995.
7. Renato Dulbecco, The Design of Life, Yale University Press, 1987. p 89.
8. Russell F. Doolittle, moderator: "The origin and subsequent evolution of spliceosomal introns," H.M.S. Beagle [no longer maintained], 5-17 Nov 1996.
9. James D. Watson, Nancy H. Hopkins, Jeffrey W. Roberts, Joan Argetsinger Steitz and Alan M. Weiner, The Molecular Biology of the Gene, 4th edition, Menlo Park, California: The Benjamin/Cummings Publishing Company, Inc., 1987. p 629.
10. Steven Zimmerly, Huatao Guo, Phillip S. Perlman and Alan M. Lambowitz, "Group II Intron Mobility Occurs by Target DNA-Primed Reverse Transcription," p 545-554 v 82 Cell, 25 August 1995.
11. Jian Yang, Steven Zimmerly, Peter Perlman and Alan M. Lambowitz, "Efficient integration of an intron RNA into double-stranded DNA by reverse splicing," p 332-335 v 381 Nature, 23 May 1996.
12. Benoit Cousineau et al., "Retrohoming of a Bacterial Group II Intron: Mobility via Complete Reverse Splicing, Independent of Homologous DNA Recombination," p 456-462 v 94 Cell, 21 August 1998.
13. Arlin Stoltzfus, John M. Logsdon Jr., Jeffrey D. Palmer, and W. Ford Doolittle. "Intron 'sliding' and the diversity of intron positions" [abstract], p 10739-10744 v 94, Proc. Natl. Acad. Sci. USA, September 1997.
14. Manyuan Long, Sandro J. de Souza, Carl Rosenberg and Walter Gilbert. "Relationship between 'proto-splice sites' and intron phases: Evidence from dicodon analysis" [abstract], p 219-223 v 95, Proc. Natl. Acad. Sci. USA, 6 January 1998.
15. Ivan Amato, "DNA Shows Unexplained Patterns Writ Large," p 747 v 257 Science, 7 August 1992.
16. Kazimierz T. Tycowski, Mei-Di Shu and Joan A. Steitz. "A mammalian gene with introns instead of exons generating stable RNA products," p 464-466 v 379 Nature, 1 February 1996.