less than 3 per cent in people. Worse, there was emerging evidence that we human beings did not seem to have the heaviest genomes or the most DNA. Humble protozoa, onions and salamanders have far bigger genomes. Grasshoppers have three times as much; lungfish forty times as much. Known by the obscure name of the ‘c-value paradox’, this enigma exercised the minds of some of the most eminent scientists of the day. One of them, Susumu Ohno, coined the term ‘junk DNA’, arguing that much of the DNA might not be under selection – that is to say, might not be being continuously honed by evolution to fit a function of the body.
He was not saying it was garbage. As Sydney Brenner later made plain, people everywhere make the distinction between two kinds of rubbish: ‘garbage’ which has no use and must be disposed of lest it rot and stink, and ‘junk’, which has no immediate use but does no harm and is kept in the attic in case it might one day be put back to use. You put garbage in the rubbish bin; you keep junk in the attic or garage.
Yet the resistance to the idea of junk DNA mounted. As the number of human genes steadily shrank in the 1990s and 2000s, so the desperation to prove that the rest of the genome must have a use (for the organism) grew. The new simplicity of the human genome bothered those who liked to think of the human being as the most complex creature on the planet. Junk DNA was a concept that had to be challenged. The discovery of RNA-coding genes, and of multiple control sequences for adjusting the activity of genes, seemed to offer some straws of hope to grasp. When it became clear that on top of the 5 per cent of the genome that seemed to be specifically protected from change between human beings and related species, another 4 per cent showed some evidence of being under selection, the prestigious journal Science was moved to proclaim ‘no more junk DNA’. What about the other 91 per cent?
In 2012 the anti-junk campaign culminated in a raft of hefty papers from a huge consortium of scientists called ENCODE. These were greeted, as intended, with hype in the media announcing the Death of Junk DNA. By defining non-junk as any DNA that had something biochemical happen to it during normal life, they were able to assert that about 80 per cent of the genome was functional. (And this was in cancer cells, with abnormal patterns of DNA hyperactivity.) That still left 20 per cent with nothing going on. But there are huge problems with this wide definition of ‘function’, because many of the things that happened to the DNA did not imply that the DNA had an actual job to do for the body, merely that it was subject to housekeeping chemical processes. Realising they had gone too far, some of the ENCODE team began to use smaller numbers when interviewed afterwards. One claimed only 20 per cent was functional, before insisting none the less that the term ‘junk DNA’ should be ‘totally expunged from the lexicon’ – which, as Dan Graur of the University of Houston and his colleagues remarked in a splenetic riposte in early 2013, thus invented a new arithmetic according to which 20 per cent is greater than 80 per cent.
If this all seems a bit abstruse, perhaps an analogy will help. The function of the heart, we would surely agree, is to pump blood. That is what natural selection has honed it to do. The heart does other things, such as add to the weight of the body, produce sounds and prevent the pericardium from deflating. Yet to call those the functions of the heart is silly. Likewise, just because junk DNA is sometimes transcribed or altered, that does not mean it has function as far as the body is concerned. In effect, the ENCODE team was arguing that grasshoppers are three times as complex, onions five times and lungfish forty times as complex, as human beings. As the evolutionary biologist Ryan Gregory put it, anyone who thinks he or she can assign a function to every letter in the human genome should be asked why an onion needs a genome that is about five times larger than a person’s.
Who’s resorting to a skyhook here? Not Ohno or Dawkins or Gregory. They are saying the extra DNA just comes about, there not being sufficient selective incentive for the organism to clear out its genomic attic. (Admittedly, the idea of junk in your attic that duplicates itself if you do nothing about it is moderately alarming!) Bacteria, with large populations and brisk competition to grow faster than their rivals, generally do keep their genomes clear of junk. Large organisms do not. Yet there is clearly a yearning that many people have to prefer an explanation that sees the spare DNA as having a purpose for us, not for itself. As Graur puts it, the junk critics have fallen prey to ‘the genomic equivalent of the human propensity to see meaningful patterns in random data’.
Whenever I raised the topic of junk DNA in recent years I was astonished by the vehemence with which I was told by scientists and commentators that I was wrong, that its existence had been disproved. In vain did I point out that on top of the transposons, the genome was littered with ‘pseudogenes’ – rusting hulks of dead genes – not to mention that 96 per cent of the RNA transcribed from genes was discarded before proteins were made from the transcripts (the discards are ‘introns’). Even though some parts of introns and pseudogenes are used in control sequences, it was clear the bulk was just taking up space, its sequence free to change without consequence for the body. Nick Lane argues that even introns are descended from digital parasites, from the period when an archeal cell ingested a bacterium and turned it into the first mitochondrion, only to see its own DNA invaded by selfish DNA sequences from the ingested bacterium: the way introns are spliced out betrays their ancestry as self-splicing introns from bacteria.
Junk DNA reminds us that the genome is built by and for DNA sequences, not by and for the body. The body is an emergent phenomenon consequent upon the competitive survival of DNA sequences, and a means by which the genome perpetuates itself. And though the natural selection that results in evolutionary change is very far from random, the mutations themselves are random. It is a process of blind trial and error.
Red Queen races
Even in the heart of genetics labs there is a long tradition of resistance to the idea that mutation is purely random and comes with no intentionality, even if selection is not random. Theories of directed mutation come and go, and many highly reputable scientists embrace them, though the evidence remains elusive. The molecular biologist Gabby Dover, in his book Dear Mr Darwin, tried to explain the implausible fact that some centipedes have 173 body segments without relying exclusively on natural selection. His argument was basically that it was unlikely that a randomly generated 346-legged centipede survived and bred at the expense of one with slightly fewer legs. He thinks some other explanation is needed for how the centipede got its segments. He finds such an explanation in ‘molecular drive’, an idea that remains frustratingly vague in Dover’s book, but has a strong top–down tinge. In the years since Dover put forward the notion, molecular drive has sunk with little trace, following so many other theories of directed mutation into oblivion. And no wonder: if mutation is directed, then there would have to be a director, and we’re back to the problem of how the director came into existence: who directed the director? Whence came this knowledge of the future that endowed a gene with the capacity to plan a sensible mutation?
In medicine, an understanding of evolution at the genomic level is both the problem and the solution. Bacterial resistance to antibiotics, and chemotherapeutic drug resistance within tumours, are both pure Darwinian evolutionary processes: the emergence of survival mechanisms through selection. The use of antibiotics selects for rare mutations in genes in bacteria that enable them to resist the drugs. The emergence of antibiotic resistance is an evolutionary process, and it can only be combated by an evolutionary process. It is no good expecting somebody to invent the perfect antibiotic, and find some way of using it that does not elicit resistance. We are in an arms race with germs, whether we like it or not. The mantra should always be the Red Queen’s (from Lewis Carroll’s Through the Looking-Glass): ‘Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!’ The search for the next antibiotic must begin long before the last one is ineffective.
That, after all, is how the immune system works. It does not just produce the best antibodies it can find; it sets out to experiment and evolve in real time. Human beings cannot expect to rely upon evolving resistance to parasites quickly enough by the
