Putting out the rubbish in the human genome

Gerton Lunter

The question of how many of the 3 billion letters in the human genome are doing something useful and how many are just evolutionary leftovers with no function – ‘junk DNA’ – has been difficult to answer. Now scientists from Oxford’s Medical Sciences Division, including Gerton Lunter from WTCHG and Chris Ponting from the MRC Functional Genomics Unit, have estimated the selection pressure on modern genetic elements over 100 million years of evolution, and concluded that only around 8 per cent of our DNA actually does something important.

The notion of ‘junk DNA’ arose from the finding that only about 1.5 per cent of our genome encodes the proteins that compose the living body. In recent years further studies have found that some sites between protein coding regions may have important roles in regulating the expression of the genes. In 2012 scientists involved in the ENCODE (Encyclopedia of DNA Elements) project raised the stakes by announcing that 80 per cent of the human genome was in some way or another involved in ‘biochemical function’.

The claim was controversial, with many in the field arguing that their definition of ‘function’ was too broad. Lunter, Ponting and their colleagues have taken a different approach, simply asking whether any given piece of DNA has survived the rigours of natural selection over millions of years, which would imply that it is too important for the species in question to lose.

The Oxford scientists carried out pairwise comparisons between human DNA and the DNA of several other species, including horses, bushbabies and mice. These species diverged from the human lineage up to 100 million years ago. As they report in a recent issue of PLoS Genetics, they find that only around 8 per cent of human DNA is encoding important functions at any point in time. The amount of functional DNA shared between any two species is inversely related to the time since they diverged. Only 2.2 per cent is shared between a human and a mouse, the most distantly related species in the study, implying that these elements, which are almost all in protein coding regions, are the minimal set needed to be a mammal.  The remainder of the 8 per cent have undergone rapid and dynamic turnover in the form of losses, gains or substitutions.  While functional, these elements are not shared between species, and will include elements encoding for species-specific biology.   But the vast majority of our genome, 92 per cent, has clearly not affected the survival of the species, and may indeed qualify for the label ‘junk’.

‘Evolution is more dynamic than we thought’, says Gerton Lunter, ‘but most of the changes are irrelevant. If you’re interested in looking for mutations that have a bearing on human disease, it’s important to know where to look.’

Chris M Rands, Stephen Meader, Chris P Ponting, and Gerton Lunter. 8.2% of the human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genetics 2014: published online 24 July doi: doi/pgen.1004525

See also:

Less than 10% of human DNA has functional role, claim scientists (The Guardian, 25 July 2014)