In a recent paper, Morris and Mattick (2014) claim that:
“The discovery of introns in 1977 was perhaps the biggest surprise in the history of molecular biology, as no one expected that the genes of higher organisms would be mosaics of coding and non-coding sequences, all of which are transcribed. However, the prevailing concept of the flow of genetic information was not overly disturbed, as the removal of the intervening sequences (that is, introns) and the reconstruction of a mature mRNA by splicing preserved the conceptual status quo; that is, genes still made proteins. In parallel, it was assumed that the excised intronic RNAs were simply degraded, although the technology of the time was too primitive to confirm this. In any case, introns were immediately and universally dismissed as genomic debris, and their presence was rationalized as evolutionary remnants involved in the prebiotic modular assembly of protein-coding RNAs that have remained (and been expanded by transposition) in complex organisms. This notion was consistent, at least superficially, with the implication of the C-value enigma that eukaryotes contained varying amounts of DNA ‘baggage’. It is also in agreement with the accompanying conclusion that retrotransposon sequences are mainly ‘selfish’, parasitic DNA.”
Morris, K.V. and J.S. Mattick (2014). The rise of regulatory RNA. Nature Reviews Genetics, in press.
So, let’s check the actual literature of the time and see if their version is correct:
“Perhaps the most surprising discovery in the initial studies of eukaryotic gene structure has been that many genes contain interruptions in the coding sequences. The origin and the function of these intervening sequences (IVS or introns) are not yet well understood but are the subject of intense investigation.”
Wallace, R.B., P.F. Johnson, S. Tanaka, M. Schöld, K. Itakura, and J. Abelson. 1980. Directed deletion of a yeast transfer RNA intervening sequence. Science 209: 1396-1400.
“Since the discovery that many eukaryotic genes are discontinuous, a number of studies have been directed towards identifying a function for intervening sequences (IVSs).”
Johnson, P.F. and J. Abelson. 1983. The yeast tRNA(tyr) gene intron is essential for correct modification of its tRNA product. Nature 302: 681-687.
“It is possible that the relationship between the location of the splice junction in the gene at the surface of the protein confers a biological advantage and hence is a result of natural selection. Introns and their associated splicing systems could be exploited in many ways during the evolution of a protein.”
Craik, C.S., S. Sprang, R. Fletterick, and W.J. Rutter. 1982. Intron-exon splice junctions map at protein surfaces. Nature 299: 180-182.
“We conclude from this experiment that the intron in the yeast actin gene does not have an observable function. It is possible that the role of the intron is too subtle to be observed in laboratory conditions of growth or that the intron, while having evolutionary significance, has no present role. To conclude that this is true for all yeast genes that contain introns would of course be premature, but there exist strains in which mitochondrial introns have been removed with no observable effect.”
Ng, R., H. Domdey, G. Larson, J.J. Rossi, and J. Abelson. 1985. A test for intron function in the yeast actin gene. Nature 314: 183-184.
“Solutions to problems of how introns are dealt with by cells do not address the question of why introns are there at all, questions about intron function. Some introns in some genes perform clearly regulatory roles, since splicing factors specific to the tissue or developmental stage decide when and where splicing should occur (Breitbart et al. 1985). In addition, some introns in some genes contain enhancers or modulators of the expression of those genes (Slater et al. 1985). However, the great majority of introns in protein-coding genes have no such “functions.” Direct experimental as well as indirect comparative data show that most introns can be removed from genes without phenotypic effect (Blake 1985). Thus, in terms of beneficial effects on the fitnesses of organisms, we almost certainly cannot account for the presence of the majority of individual introns, nor for the propensity to have introns at all, even though introns may on the average represent as much as 90% of the length of a gene and perhaps as much as half of the total DNA in some complex eukaryotes such as humans.”
Doolittle, W.F. 1987. The origin and function of intervening sequences in DNA: a review. American Naturalist 130: 915-928.
“Ever since the discovery of split genes, there has been a debate about why they are split. This can be resolved into three separate problems: the origin of the introns that split the genes (separating exons from each other), the role of introns in evolution, and their present function, if any.”
Rogers, J. 1985. Exon shuffling and intron insertion in serine protease genes. Nature 315: 458-459.
“These conserved sequences, especially those found in the introns, suggest a role for internal sequences in the regulation of β-actin gene expression.”
Ng, S.-Y., P. Gunning, R. Eddy, P. Ponte, J. Leavitt, T. Shows, and L. Kedes. 1985. Evolution of the functional human β-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Molecular and Cellular Biology 5: 2720-2732.
“The advantage to the organism to remove intron 1 last is unclear but could point to some as yet undetermined function for this intron. In support of this, we have found that a DNA probe derived from intron 1 hybridizes to a single fragment in a Southern blot of total mouse genomic DNA indicating that the sequences in this intron may be conserved, whereas a DNA probe derived from intron 2 does not hybridize.”
Wells, D., D. Hoffman, and L. Kedes. 1987. Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the human H3.3 histone multigene family. Nucleic Acids Research 15: 2871-2889.
1993 Nobel Prize in Physiology or Medicine
to Richard J. Roberts and Phillip A. Sharp
For their discovery of split genes
“Roberts’ and Sharp’s discovery has changed our view on how genes in higher organisms develop during evolution. The discovery also led to the prediction of a new genetic process, namely that of splicing, which is essential for expressing the genetic information. The discovery of split genes has been of fundamental importance for today’s basic research in biology, as well as for more medically oriented research concerning the development of cancer and other diseases.”
“As a consequence of the discovery that genes are often split, it seems likely that higher organisms in addition to undergoing mutations may utilize another mechanism to speed up evolution: rearrangement (or shuffling) of gene segments to new functional units. This can take place in the germ cells through crossing-over during pairing of chromosomes. This hypothesis seems even more attractive following the discovery that individual exons in several cases correspond to building modules in proteins, so-called domains, to which specific functions can be attributed. An exon in the genome would thus correspond to a particular subfunction in the protein and the rearrangement of exons could result in a new combination of subfunctions in a protein. This kind of process could drive evolution considerably by rearranging modules with specific functions.”