Junk is not the same as garbage
There is a close homology with computer viruses, which did not yet exist when Dawkins suggested the genetic version of the concept of digital parasitism. Some of the transposons, the SINEs, appear to be parasites of parasites, because they use the apparatus of longer, more complete sequences to get themselves disseminated. For all the heroic attempts to see their function in terms of providing variability that might one day lead to a brave new mutation, the truth is that their more immediate and frequent effect is occasionally to disrupt the reading of genes.
Of course, these selfish DNA sequences can thrive only because a small percentage of the genome does something much more constructive – builds a body that grows, learns and adapts sufficiently to its physical and social environment that it can eventually thrive, attract a mate and have babies. At which point the selfish DNA says, ‘Thank you very much, we’ll be making up half the sequence in the children too.’
It is currently impossible to explain the huge proportion of the human genome devoted to these transposons except by reference to the selfish DNA theory. There’s just no other theory that comes close to fitting the facts. Yet it is routinely rejected, vilified and ‘buried’ by commentators on the fringe of genetics. The phrase that really gets their goat is ‘junk DNA’. It’s almost impossible to read an article on the topic without coming across surprisingly passionate denunciations of the ‘discredited’ notion that some of the DNA in a genome is useless. ‘We have long felt that the current disrespectful (in a vernacular sense) terminology of junk DNA and pseudogenes,’ wrote Jürgen Brosius and Stephen Jay Gould in an early salvo in 1992, ‘has been masking the central evolutionary concept that features of no current utility may hold crucial evolutionary importance as recruitable sources of future change.’ Whenever I write about this topic, I am deluged with moralistic denunciations of the ‘arrogance’ of scientists for rejecting unknown functions of DNA sequences. To which I reply: functions for whom? The body or the sequences?
This moral tone to the disapproval of ‘so-called’ junk DNA is common. People seem to be genuinely offended by the phrase. They sound awfully like the defenders of faith confronted with evolution – it’s the bottom–up nature of the story that they dislike. Yet as I shall show, selfish DNA and junk DNA are both about as accurate as metaphors ever can be. And junk is not the same as garbage.
What’s the fuss about? In the 1960s, as I mentioned earlier, molecular biologists began to notice that there seemed to be far more DNA in a cell than was necessary to make all the proteins in the cell. Even with what turned out to be a vastly over-inflated estimate of the number of genes in the human genome – then thought to be more than 100,000, now known to be about 20,000 – genes and their control sequences could account for only a small percentage of the total weight of DNA present in a cell’s chromosomes, at least in mammals. It’s 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