At least 75 per cent of our DNA really is useless junk after all

You’re far from a perfect product. The code that makes us is at least 75 per cent rubbish, according to a study that suggests most of our DNA really is junk after all.

After 20 years of biologists arguing that most of the human genome must have some kind of function, the study calculated that in fact the vast majority of our DNA has to be useless. It came to this conclusion by calculating that, because of the way evolution works, we’d each have to have a million children, and almost all of them would need to die, if most of our DNA had a purpose.

But we each have just a few children on average, and our genetic health is mostly fine. The study therefore concludes that most of our DNA really must be junk – a suggestion that contradicts controversial claims to the contrary from a group of prominent genomics researchers in 2012.

Junk or not?

When researchers first worked out how DNA encodes the instructions for making proteins in the 1950s, they assumed that almost all DNA codes for proteins. However, by the 1970s, it was becoming clear that only a tiny proportion of a genome encodes functional proteins – about 1 per cent in the case of us humans.

Biologists realised that some of the non-coding DNA might still have an important role, such as regulating the activity of the protein-coding genes. But around 90 per cent of our genome is still junk DNA, they suggested – a term that first appeared in print in a 1972 article in New Scientist.

But throughout the 2000s, a number of studies purported to show that junk DNA was nothing of the sort, based on demonstrating that some tiny bits of non-coding DNA had some use or other. These claims proved popular with creationists, who were struggling to explain why an intelligently designed genome would consist mostly of rubbish.

The grandest claim came in 2012, when a consortium of genomics researchers called ENCODE declared that, according to their project, a huge 80 per cent of the DNA in the human genome has a function. “They had spent $400 million, they wanted something big to say,” says Dan Graur of the University of Houston.

Graur is one of many researchers who didn’t believe ENCODE’s claim. The heart of the issue is how you define functional. ENCODE defined DNA as such if it showed any “biochemical activity”, for instance, if it was copied into RNA. But Graur doesn’t think a bit of activity like this is enough to prove DNA has a meaningful use. Instead, he argues that a sequence can only be described as functional if it has evolved to do something useful, and if a mutation disrupting it would have a harmful effect.

Millions of children

Mutations to DNA happen at random for several reasons, such as UV radiation or mistakes made when DNA replicates during cell division. These mutations change one base of DNA into another – an A to a T, for example – and when they occur in a gene are more likely to be harmful than beneficial.

When we reproduce, our children inherit a shuffled bag of mutations, and those with a collection of particularly bad ones are more likely to die before having children of their own. This is how evolution stops bad mutations building up to dangerously high levels in a species.

Following Graur’s logic, if most of our DNA is functional, we would accumulate a large proportion of harmful mutations in important sequences. But if most of our DNA is junk, the majority of mutations would have no effect.

Graur’s team have now calculated how many children a couple would need to conceive so evolution could weed out enough bad mutations from our genomes as fast as they arise. If the entire genome was functional, couples would need to have around 100 million children, and almost all would have to die. Even if just a quarter of the genome is functional, each couple would still have to have nearly four children on average, with only two surviving to adulthood, to prevent harmful mutations building up to dangerous levels.

Taking into account estimates of the mutation rate and average prehistorical reproduction rate, Graur’s team calculated that only around 8 to 14 per cent of our DNA is likely to have a function.

Less than an onion

This ties in nicely with a 2014 study that compared our genome with other species and concluded that around 8 per cent of it is functional.

“The findings are entirely supportive of one another,” says one of the authors of the 2014 study, Chris Ponting of the University of Edinburgh, UK. “We are walking around with a genome where only 1 in 10 bases actually matters.”

We don’t know how much of our DNA has a non-sequence-related function, says Ryan Gregory of the University of Guelph in Canada. Some regions of DNA are useful without having an important sequence, so mutations in these areas probably don’t matter. But even taking this into account, most DNA is probably junk, says Gregory.

The challenge for those who think most non-coding DNA is vital is to explain why an onion needs five times as much of it as we do, says Gregory. “I would like to think that most knowledgeable biologists who properly appreciate evolutionary theory and genomic diversity are well aware of the many problems with ENCODE’s claim,” he says.

But most people and even some scientists are uncomfortable with the idea that most of their DNA is junk, says Ponting. Even worse for such people, other genomic studies are now revealing that we all carry plenty of mutations that affect both our coding DNA and non-coding DNA. While evolution weeds out some of the worst ones, this doesn’t stop plenty of mutations collecting in our genome.

“We are walking around as individuals with relatively large numbers of our genes not working properly,” he says. “These are ideas some find shocking.”

Journal reference: Genome Biology and Evolution, DOI: 10.1093/gbe/evx121