Mystery of Intron Gain

Abstract

For nearly 15 years, it has been widely believed that many introns were recently acquired by the genes of multicellular organisms. However, the mechanism of acquisition has yet to be described for a single animal intron. Here, we report a large-scale computational analysis of the human, Drosophila melanogaster, Caenorhabditis elegans, and Arabidopsis thaliana genomes. We divided 147,796 human intron sequences into batches of similar lengths and aligned them with each other. Different types of homologies between introns were found, but none showed evidence of simple intron transposition. Also, 106,902 plant, 39,624 Drosophila, and 6021 C. elegans introns were examined. No single case of homologous introns in nonhomologous genes was detected. Thus, we found no example of transposition of introns in the last 50 million years in humans, in 3 million years in Drosophila and C. elegans, or in 5 million years in Arabidopsis. Either new introns do not arise via transposition of other introns or intron transposition must have occurred so early in evolution that all traces of homology have been lost.[A. Smit and P. Green kindly provided computer programs.]When introns were first discovered in 1977, an immediate question was where do they come from? Very early in the debate, Crick and others suggested that new introns might arise as transposons that either come equipped with or quickly acquire signals sufficient for splicing (Crick 1979). This idea was reinforced by the finding by Dibb and Newman (1989) that introns tend to arise at sites with a consensus sequence of (C/A)AG|R, which they interpreted in terms of sequence-specific targeting of some notyet-characterized insertion machinery. However, small-scale comparisons of intron sequences have turned up no evident transposition events, and there is to date a sole convincing demonstration of the creation of an intron from a transposable element, in plants ( Giroux et al. 1994).Yet, it is becoming increasingly clear that some introns have arisen very recently. There is a growing collection of introns found at positions in one species at which closely related species have no intron (Palmer and Logsdon Jr. 1991;Logsdon Jr. et al. 1995;Rzhetsky et al. 1997;Frugoli et al. 1998;Gotoh 1998;Tarrio et al. 1998;Venkatesh et al. 1999; for an insightful review, see Logsdon Jr. et al. 1998;Lynch and Richardson 2002). Over a longer time scale, only 14% of animal intron positions match with the intron positions of homologous plant genes, indicating that, if gain is a primary mechanism of intron discordance, 60%-80% percent of contemporary animal introns were acquired after the evolutionary divergence of animals and plants (Fedorov et al. 2002).Such new introns should not be hard to find. For instance, the human genome has 31,000 intron-containing genes with 160,000 introns. If 60% of these introns were acquired since the animal-plant divergence then there have been an average of 20-50 cases of intron insertion per million years of human evolution. This estimation is also in accordance w...

Alternative splicing: A missing piece in the puzzle of intron gain

“…Genome scans carried out in human, D. melanogaster, C. elegans, and A. thaliana could not detect a single case of homologous introns in nonhomologous genes (31). Subsequent studies in Drosophila, Caenorhabditis, and rice searching specifically for donors of introns supposed to be novel because of restricted phylogenetic distribution (15,18,20) also have been fruitless (7,18,22,23).…”

Three distinct modes of intron dynamics in the evolution of eukaryotes

“…There is a growing body of evidence that intron loss and, especially, intron gain have been extremely rare in several eukaryotic lineages in the last ∼100-200 million yr (Fedorov et al 2003;Babenko et al 2004;Roy and Hartl 2006;Penny 2006, 2007;Coulombe-Huntington and Majewski 2007). Ignoring for the time being the lineage-specific trends, simple averaging lends strong support to this conclusion (Fig.…”

“…It is generally accepted that vertebrates have gained very few introns, if any (Fedorov et al 2003;Babenko et al 2004;CoulombeHuntington and Majewski 2007). Nematodes are characterized by a high number of events, with losses being more plentiful than gains (Cho et al 2004;Coghlan and Wolfe 2004).…”

“…The inverse approach was adopted by Qiu et al (2004), who assumed that the rates of intron gain and loss are different between genes, but for a particular gene remain constant across the entire phylogenetic tree. The latter assumption is hard to accept given the apparent dramatic differences in the rates of intron turnover in different lineages (Fedorov et al 2003;Cho et al 2004;Roy and Hartl 2006). Recently, two ML techniques have been developed for essentially the same evolutionary model as that of Roy and Gilbert (Csuros 2005;Nguyen et al 2005).…”

Origins of recently gained introns in Caenorhabditis

“…Recent intron losses are also frequently seen in plant genes (7). Fedorov et al (8) did not detect any recently duplicated (i.e., gained) introns within the genome sequences of human, Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. Finding recent intron gains and identifying the origin of their DNA is likely to be a key to understanding where new introns come from.…”