Oxford University scientists report that only 8.2% of human DNA is likely to be doing something important, i.e., is functional. This number is quite different from one given in 2012, when a number of researchers involved in the ENCODE (Encyclopedia of DNA Elements) project stated that 80% of our genome has some biochemical function.
According to the Oxford team, which published its study (“8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage”) in PLOS Genetics, the 80% claim has been controversial, with many in the field arguing that the biochemical definition of 'function' was too broad—that just because an activity on DNA occurs, it does not necessarily have a consequence. For functionality you need to demonstrate that an activity matters.
To reach their figure, the Oxford University group took advantage of the ability of evolution to discern which activities matter and which do not. They identified how much of our genome has avoided accumulating changes over 100 million years of mammalian evolution—a clear indication that this DNA matters; it has some important function that needs to be retained.
“Constrained DNase 1 hypersensitivity sites, promoters, and untranslated regions have been more evolutionarily stable than long noncoding RNA loci, which have turned over especially rapidly,” wrote the investigators. “By contrast, protein coding sequence has been highly stable, with an estimated half-life of over a billion years (d1/2 = 2.1–5.0). From extrapolations we estimate that 8.2% (7.1–9.2%) of the human genome is presently subject to negative selection and thus is likely to be functional, while only 2.2% has maintained constraint in both human and mouse since these species diverged. These results reveal that the evolutionary history of the human genome has been highly dynamic, particularly for its noncoding yet biologically functional fraction.”
“This is in large part a matter of different definitions of what is 'functional' DNA,” says joint senior author Chris Pointing, Ph.D., of the MRC Functional Genomics Unit at Oxford University. “We don't think our figure is actually too different from what you would get looking at ENCODE's bank of data using the same definition for functional DNA.”
“But this isn't just an academic argument about the nebulous word function. These definitions matter. When sequencing the genomes of patients, if our DNA was largely functional, we'd need to pay attention to every mutation. In contrast, with only 8% being functional, we have to work out the 8% of the mutations detected that might be important. From a medical point of view, this is essential to interpreting the role of human genetic variation in disease.”
The researchers used a computational approach to compare the complete DNA sequences of various mammals, from mice, guinea pigs, and rabbits to dogs, horses, and humans. Gerton Lunter, Ph.D., from the Wellcome Trust Centre for Human Genetics at Oxford University, the other joint senior author, explained: “Throughout the evolution of these species from their common ancestors, mutations arise in the DNA and natural selection counteracts these changes to keep useful DNA sequences intact.”
The rest of the human genome, the non-8.2%, is leftover evolutionary material, parts of the genome that have undergone losses or gains in the DNA code, often called “junk” DNA.