Because proteins are the structure of living creatures, and because as enzymes they control the processes of life, it has seemed obvious that DNA controls life, that we can `map' DNA code on to all the important living functions. We could assign a function to each protein, so we could assume that the DNA that coded for that protein was ultimately or fundamentally responsible for the corresponding function. Dawkins's early books reinforced the idea of one gene, one protein, one function (although he carefully warned his readers that he didn't want to give that impression), and this encouraged such media exaggerations as calling the human genome the Book of Life. And the `selfish gene' image made it entirely credible that huge stretches of the genome were present for solely selfish reasons - that is, for no reason related to the organism concerned.
Biologists employed - as so many now are - in the biotechnology industries serving agriculture, pharmacy, medicine, even some engineering projects (we don't mean just `genetic engineering' but making better motor oils), all subscribe to the central dogma, with a few minor modifications and exceptions. All of them have been informed that nearly all of the DNA in the human genome is `junk', not coding for proteins, and that although some of it may be important for developmental processes or for controlling some of the `real' genes, they really don't need to worry about it.
Admittedly, quite a lot of junk DNA seems to be transcribed into RNA, but these are just short lengths that sit about briefly in the cell fluids and don't need to be considered when you're doing important proteinmaking things with the real genes. Recall that the DNA sequences of real genes consist of a mosaic of `exons' which code for proteins, separated by other sequences called introns. The introns have to be cut out of the RNA copies to get the `real' protein-coding sequences, called messenger-RNAs, which lace into ribosomes like tapes into a tape player. Messenger-RNAs determine what proteins get made, and they have sequences on their ends that label them for making many copies of a protein or for destruction after only a couple of protein molecules.
Nobody worried much about those snipped-out introns, just bits of RNA drifting aimlessly around in the cell till they got broken up by enzymes. Now, they do worry. Writing in the October 2004 Scientific American, John Mattick reports that The central dogma is woefully incomplete for describing the molecular biology of eukaryotes. Proteins do play a role in the regulation of eukaryotic gene expression, yet a hidden, parallel regulatory system consisting of RNA that acts directly on DNA, RNAs and proteins is also at work. This overlooked RNA signalling network may be what allows humans, for example, to achieve structural complexity far beyond anything seen in the unicellular world.
Petunias made that clear. In 1990 Richard Jorgensen and colleagues were trying to breed new varieties of petunias, with more interesting, brighter colours. An obvious approach was to engineer into the petunia genome some extra copies of the gene that coded for an enzyme involved in the production of pigment. More enzyme, more pigment, right?
Wrong.
Less pigment?
No, not exactly. What previously was a uniformly coloured petal became stripy. In some places the pigment was being produced, elsewhere it wasn't. This effect was so surprising that plant biologists tried to find out exactly why it was happening. And what they found was `RNA interference'. Certain RNA sequences can shut down a gene, prevent it making protein. It happens in many other organisms, too. In fact, it is extremely widespread. And it suggests something extraordinarily important.
The big question in this area, asked many times and largely ignored, has always been: if introns (which occupy all but one-twentieth of a typical protein-coding gene) have no biological function, why are they there? It is easy to dismiss them as relics of some dim evolutionary past, no longer useful, lying around because natural selection can't get rid of things that are harmless. Even so, we can still wonder whether introns are present because they do have some useful function, one that we haven't yet worked out. And it's starting to look as if that may be the case.
For a start, introns are not that ancient. It now seems that they became incorporated into the human genome relatively recently. They are probably related to mobile genetic elements known as group II introns, which are a `parasitic' form of DNA that can invade host genomes and then remove themselves when the DNA is expressed as RNA. Moreover, they now seem to have a role as 'signals' in the regulation of genetic processes. An intron may be relatively short, compared to the long protein-coding sequences that arise when the introns are snipped out, but a short signal has advantages and can do quite a lot. In effect, the introns may be genetic 'txt msgs' in the mobile phone of life. Short, cheap, and very effective. An RNA-based `code', running parallel to the DNA double helix, can affect the activity of the cell very directly. An RNA sequence can act as a very specific, well-defined signal, directing RNA molecules to their targets in RNA or DNA.
The evidence for the existence of such a signalling system is reasonable, but not yet undeniable. If such a system does exist, it clearly has the potential to resolve many biological mysteries. A big puzzle about the human genome is that its 34,000 genes manage to encode over 100,000 proteins. Clearly `one gene one protein' doesn't work. A hidden RNA signalling system could make one gene produce several proteins, depending on what the accompanying RNA signal specified. Another puzzle is the complexity of eukaryotes, especially the Cambrian explosion of 525 million years ago, when the range of terrestrial body-plans suddenly diversified out of all recognition; indeed, was more diverse than it is now. Perhaps the hypothetical RNA signalling system started to take off at that time. And it's widely known that the human and chimpanzee genomes are surprisingly similar (though the degree of similarity seems not to be 98 per cent as widely quoted even a few years ago). If our RNA signals are significantly different, that would be one way to explain why humans don't greatly resemble chimps.
At any rate, it very much looks as if all that `junk' DNA in your genome is not junk at all. On the contrary, it may be a crucial part of what makes you human.
This lesson is driven home by those business associates of parasitic wasps, the symbiotic polydnaviruses, sneakily buried inside the wasps' own DNA. There is a message there about human evolution, and it's a very strange one.
Genome-sequencing may have been oversold as the answer to human diseases, but it's very good basic science. The activities of the sequencers have revealed that wasps are not the only organisms to have bits of viral DNA hanging around in their genomes. In fact, most creatures do, humans included. The human genome even contains one complete viral genome, and only one, called ERV-3 (Endogenous RetroVirus). This may seem an evolutionary oddity, a bit of `junk DNA' that really is junk ... but, actually, without it none of us would be here. It plays the absolutely crucial role of preventing rejection of the foetus by the mother. Mother's immune system `ought to' recognise the tissue of a developing baby as `foreign', and trigger actions that will get rid of it. By `ought to' here we mean that this is what the immune system normally does for tissue that is not the mother's own.