I discussed the early papers involving the discovery of Alu elements in a previous post in the series. Unlike some transposable elements that are capable of autonomous transposition, Alu elements do not encode the requisite enzymes and depend on those of other sequences such as LINE-1 elements. Alu is restricted to primates, and its origin seems to have been a duplication and reverse transcription of a 7SL RNA gene early in primate evolution. One in ten nucleotides in each human genome is part of an Alu sequence, of which there are more than 1 million copies.
The elucidation of the evolutionary origins of Alu elements came some time after their initial discovery in 1979. Initially, it was thought that the 7SL RNA gene was derived from Alu, but the reverse conclusion was given by Ullu and Tschudi (1984) and was discussed further by authors such as Quentin (1992). As noted, the original papers reporting the existence of Alu elements raised the question about their potential functions. However, the later articles arrived right in the middle of the supposed time when non-coding DNA was dismissed as irrelevant. Once again, the actual literature from the period does not support the notion that such a dismissal ever actually occurred.
Ullu and Tschudi (1984) did not discuss possible function explicitly, but they did note that “these 7SL-specific homologies may reflect a strong functional constraint acting on these sequences.” In an accompanying article in the same issue of Nature, Brown (1984) was more specific about the significance of the results. He stated,
Ullu and Tschudi suggest that Alu sequences represent defective 7SL RNA molecules that have been reverse-transcribed into DNA and inserted into the genome. An analogous origin has been suggested for alpha-globin pseudogenes in the mouse, and the multiple pseudogenes for small nuclear RNAs in man. Pseudogenes are generally thought not to play an important role in the cell. Perhaps those who have argued that Alu, by its very abundance, must have an important function will recognize that this argument has now lost some of its weight.
Two important things are expressed here. One, the assumption that Alu elements are functional because they are abundant (i.e., an adaptationist expectation that they would have been removed otherwise) was apparently common in the early 1980s. Indeed, that’s why the “selfish DNA” idea was proposed (Orgel and Crick 1980; Doolittle and Sapienza 1980). Two, pseudogenes — defunct coding genes — were indeed thought to be non-functional, for obvious reasons. These are the sequences to which the term “junk DNA” originally related.
Additional information regarding the origin of Alu sequences was provided by Quentin (1992), who said,
from the beginning, the Alu progenitor sequences could have retained the capacity to interact with cellular components, suggesting that they are functionally important for the host genome. On the other hand, this RNA secondary structure could have some affinity for reverse transcriptases or other components of the retroposition machinery, and its conservation in the monomeric and Alu dimeric sequences could be related to their mobility. Indeed, this structure is first found in the 7SL RNA sequences that are prone to retroposition, and it is also retained by the progenitor sequences of the Bl family in the rodent genomes. Nevertheless, both hypotheses (secondary structure involved in a cellular function or in the reverse transcription) are not mutually exclusive.
Yet, here is a fairly typical introduction from a recent paper about Alu (Hasler and Strub 2006):
Alu elements, as well as other repetitive elements, were at the origin considered as parasites of the genome that had no major effect on its stability and genic expression. They were thought to be â€˜selfishâ€™ or â€˜junkâ€™DNA (6,7), but nowadays, several lines of evidence show that the presence of repetitive elements and especially of Alu elements, had a great influence on the human genome, in particular on its evolution. These effects were both negative and positive. On one hand, integration into genic regions that caused gene inactivation might often have been deleterious for the organism. On the other hand, because of their extended sequence homology, Alu elements induced a considerable number of non-allelic recombinations that lead to both duplications and deletions of DNA segments, thereby accelerating evolution by several orders of magnitude. Another function frequently attributed to Alu elements is their ability to provide new regulatory elements to neighboring genes. It was, indeed, reported several times that Alu elements became effectors of gene transcription by providing new enhancers, promoters and polyadenylation signals to many genes.
The only authors cited for the “Alu is just junk” are Orgel and Crick (1980) and Orgel et al. (1980). I have discussed these articles before, but will reiterate one statement from each.
Orgel and Crick (1980):
It would be surprising if the host genome did not occasionally find some use for particular selfish DNA sequences, especially if there were many different sequences widely distributed over the chromosomes. One obvious use … would be for control purposes at one level or another.
Orgel et al. (1980):
In our recent experience most people will agree, after discussion, that ignorant DNA, parasitic DNA, symbiotic DNA (that is, parasitic DNA which has become useful to the organism) and ‘dead’ DNA of one sort or another are all likely to be present in the chromosomes of higher organisms. Where people differ is in their estimates of the relative amounts. We feel that this can only be decided by experiment.
Part of the Quotes of interest series.
Brown, A.L. 1984. On the origin of the Alu family of repeated sequences. Nature 312: 106.
Hasler, J. and K. Strub. 2006. Alu elements as regulators of gene expression. Nucl. Acids Res. 34: 5491-5497.
Orgel, L.E. and F.H.C. Crick. 1980. Selfish DNA: the ultimate parasite. Nature 284: 604-607.
Orgel, L.E., F.H.C. Crick, and C. Sapienza. 1980. Selfish DNA. Nature 288: 645-646.
Quentin, Y. 1992. Origin of the Alu family: a family of Alu-like monomers gave birth to the left and right arms of the Alu elements. Nucl. Acids Res. 20: 3397-3401.
Ullu, E. and C. Tschudi. 1984. Alu sequences are processed 7SL RNA genes. Nature 312: 171-172.