Similarly, genetic assimilation provides a much better explanation than Lamarckism for the phocomelic children of thalidomide-modified parents. We have selected, from some 4 million foetuses, those that respond to thalidomide with phocomelia. It is not surprising that when they marry each other, they produce a few progeny whose threshold is very low – below zero in fact. They are so liable to produce phocomelia that they do it without thalidomide, just as Waddington’s flies came to produce cross-veinlessness without warming the pupae.
*
One of the things that really worried Darwin was the existence of parasitic wasps – a fact that has influenced our Discworld tale, but has gone unremarked until now in the scientific commentaries. Parasitic wasps lay their eggs in other insects’ larvae, so that as the wasp eggs grow into wasp larvae, they eat their hosts. Darwin could see how this might have happened on evolutionary grounds, but it seemed to him to be rather immoral. He was aware that wasps don’t have a sense of morality, but he saw it as some kind of flaw on the part of the wasps’ creator. If God designed each species on Earth, for a special purpose – which is what most people believed at the time – then God had deliberately designed parasitic wasps, whose purpose was to eat other species of insect, also designed by God. To be so eaten, presumably.
Darwin was fascinated by such wasps, ever since he first encountered them in Botafogo Bay, Brazil. He eventually satisfied himself – though not his successors – that God had found it necessary to permit the existence and evolution of parasitic wasps in order to get to humans. This is what the quote at the end of Chapter 10 alludes to. That particular explanation has fallen out of favour among biologists, along with all theist interpretations. Parasitic wasps exist because there is something for them to parasitise – so why not? Indeed, parasitic wasps play a major role in controlling many other insect populations: nearly one-third of all of the insect populations that humans like to label ‘pests’ are kept at bay in this manner. Maybe they were created in order for humans to be possible … At any rate, the wasps that so puzzled Darwin still have much to tell us, and the latest discovery about them threatens to overturn several cherished beliefs.
Strictly, the discovery is not so much about the wasps, as about some viruses that infect them … or are symbiotic with them. They are called polydnaviruses.
When mother wasp injects her eggs into some unsuspecting larva, such as a caterpillar, she also injects a solid dose of viruses, among them said polydnaviruses. The caterpillar not only gets a parasite, it gets an infection. The virus’s genes produce proteins that interfere with the caterpillar’s own immune system, stopping it reacting to the parasite and, perhaps, rejecting it. So the wasp larvae munch merrily away on the caterpillar, and in the fullness of time they develop into adult wasps.
Now, any self-respecting adult parasitic wasp obviously needs its own complement of polydnaviruses. Where does it get them? From the caterpillar that it fed on. And it gets them (just as mother did) not as a separate infective ‘organism’, but as what is called a provirus: a DNA sequence that has been integrated into the wasp’s own genome.
Many genomes, probably most if not all, include various bits of viruses in this way. Our own certainly does. Transport of DNA by viruses seems to have been an important feature of evolution.
In 2004 a team headed by Eric Espagne worked out the DNA sequence of a polydnavirus – as one does – and what they found was dramatically different from what anyone had expected. Typical virus genomes are very different from those of ‘eukaryotes’ – organisms whose cells have a nucleus, which includes most multi-cellular creatures and many single-celled ones, but not bacteria. The DNA sequences of most eukaryote genes consist of ‘exons’, short sequences that collectively code for proteins, separated by other sequences called introns, which get snipped out when the code is turned into the appropriate protein. Viral genes are relatively simple, and typically they do not contain introns. They consist of connected code sequences that specify proteins. This particular polydnavirus genome, in contrast, does contain introns, quite a lot of them. The genome is complex, and looks much more like a eukaryote genome than a virus genome. The authors conclude that polydnavirus genomes constitute ‘biological weapons directed by the wasps against their hosts’. So they look more like the enemy’s genome than that of an ordinary virus.
*
Numerous examples, old and new, disprove every aspect of the folk version of evolution and DNA. We end with one that looks especially important, discovered very recently, and whose significance is just becoming seriously apparent to the biological community. It is probably the most severe shock that cell biology has received since the discovery of DNA and the wonderful ‘central dogma’: DNA specifies messenger-RNA which specifies proteins. The discovery was not made through some big, highly publicised research programme like the human genome project. It was made by someone who wondered why his petunias had gone stripy. When all the world is chasing ‘the’ human genome, it’s not easy to get research grants to work on stripy petunias. But what the petunias revealed is probably going to be far more important for medicine than the entire human genome project.
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 protein-making 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 colo
urs. 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 fetus 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.
Apparently, the ERV-3 protein closely resembles another one called p15E, which is part of a widespread defence system used by viruses to stop their hosts killing them off. The p15E protein stops lymphocytes, a key type of cell in the immune system, from responding to antigens, molecules that reveal the virus’s foreign nature. At some stage during mammalian evolution, this defence system was stolen from the viruses and used to stop the female placenta responding to antigens that reveal the foreign nature of the fetus’s father. Perhaps on the principle of being hung for a sheep as well as for a lamb, the human genome decided to go the whole hog3 and steal the entire retroviral genome.
When evolution carried out the theft, however, it did not just dump its booty into the human DNA sequence unchanged. It threw in a couple of introns, too, splitting ERV-3 into several separate pieces. It’s complete, but not connected. No matter: enzymes can easily snip out the introns when that bit of DNA is turned into protein. But no one knows why the introns are there. They might be an accidental intrusion. Or – pursuing the RNA interference idea – they might be much more significant. Those introns might be an important part of the genetic regulatory system, ‘text messages’ that let the placenta use ERV-3 without running the risk of setting the corresponding virus loose.
At any rate, whatever the introns are for, warm-bloodedness is not the only trick that mammalian evolution managed to find and exploit. It also indulged in wholesale theft of a virus’s genome, to stop mother’s immune system booting out baby because it ‘smelled’ of father. And we also get another lesson that DNA isn’t selfish. ERV-3 is present in the human genome, but not because it’s a bit of junk that gets copied along with everything else and has remained because it does no harm. It’s there because, in a very real sense, humans could not survive – could not even reproduce – without it.
1 They made exceptions for manifestly ‘unimportant’ but very diverse sets of alleles like blood groups, but in those cases it didn’t seem to matter much which kind you had.
2 That’s very important for a few species. Zebra-fish eggs in the wild must hatch in just under 72 hours, because they’re laid just before dawn and must hide before the third dawn when predators could see them.
3 Sorry about the proliferation of barnyard metaphors.
TWENTY-ONE
NOUGAT SURPRISE
THE ACTIVITY IN THE GREAT HALL was slowing down now. All along the rainbow lines of time, the nodes were closed. Or shut, or denoded, Rincewind thought. Whatever you did with nodes, anyway. There was a little cheer as the last glowing wizard symbol faded away, and a roar from outside as three wizards and a lot of tentacles landed in the fountain. Rincewind had been surprised about that, and then dismayed. Since it did not have his name on it, this meant that Ridcully had something worse in mind.
‘Looks like I’m not needed now,’ he said hopefully, just in case.
‘Haha, professor, what a card you are and no mistake,’ said the lobster next to him. ‘The Archchancellor was very definite that we was to keep you here no matter what you said.’
‘But I wasn’t running away!’
‘No, you was only inspecting the wall with the loose bricks in it,’ said the lobster.1 We quite understand. Lucky for you we caught you before you dropped over into the alley, eh? Could’ve done yerself a mischief.’
Rincewind sighed. The lobsters were always hard to outrun. They hunted in packs, appeared to share a common brain, and many years of harrying erring students had given them a malignant street cunning that verged on the supernatural.
Some of the senior wizards swept in … There was an argument going on between Ridcully and the Dean.
‘I don’t see why
I shouldn’t.’
‘Because you get too excited in the presence of combat, Dean. You run around making silly “hut, hut” noises,’ said Ridcully. ‘Remember why we had to stop those paintball afternoons? You didn’t seem to be able to get the hang of the term “people on my side”.’
‘Yes, but this is—’
‘It took us a week to get the Senior Wrangler looking halfway suitable for polite company – Ah, Rincewind. Still with us, I see. Good man. Very well, Mr Stibbons: report!’
Ponder coughed.
‘Hex confirms that, er, that our recent activities may have left camiloops between our word and Roundworld, sir. That is to say, residual connections that may be used deliberately or inadvertently from either side. Magic doors, in fact, drifting without anchor. These will evaporate within a matter of days. Um …’
‘I don’t want to hear “um”, Mr Stibbons. “Um” is not a word we entertain here.’
‘Well, the fact is that since the camiloops are spread over centuries, the Auditors may very well have been in Roundworld for some time. We have no way of knowing for how long. Hex, um, sorry, does report some circumstantial evidence that humans are dimly aware of their malign meddling, albeit at a very mundane level as evidenced by the findings of a researcher called Murphy. Roundworld would be difficult for them. They would be bewildered. Things would not work the way they expect. They are not flexible thinkers.’
Science of Discworld III Page 28