According to a group of genetic scientists led by Dr Gerton Lunter of the University of Oxford’s Wellcome Trust Centre for Human Genetics, only 8.2 percent of human genome is likely to be doing something important.
Illustration of a DNA molecule. Image credit: Christoph Bock, Max Planck Institute for Informatics / CC BY-SA 3.0.
This figure is very different from one given in 2012 by researchers from the Encyclopedia of DNA Elements (ENCODE) project, who stated that about 80 percent of human DNA has some biochemical function.
That claim has been controversial, with researchers 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 the new figure, Dr Lunter and his colleagues 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.
They used a computational approach to compare the complete DNA sequences of various mammals, from mice, guinea pigs and rabbits to dogs, horses and humans.
“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,” explained Dr Lunter, the senior author of a paper published in the open-access journal PLoS Genetics.
The idea was to look at where insertions and deletions of chunks of DNA appeared in the genomes of mammals. These could be expected to fall approximately randomly in the sequence – except where natural selection was acting to preserve functional DNA, where insertions and deletions would then lie further apart.
“We found that 8.2 percent of our human genome is functional. We cannot tell where every bit of the 8.2 percent of functional DNA is in our genomes, but our approach is largely free from assumptions or hypotheses. For example, it is not dependent on what we know about the genome or what particular experiments are used to identify biological function,” Dr Lunter said.
Dr Chris Rands of the University of Oxford, who is the first author on the study, added: “not all of the 8.2 percent is equally important. A little over 1 percent of human DNA accounts for the proteins that carry out almost all of the critical biological processes in the body.”
The other 7 percent is thought to be involved in the switching on and off of genes that encode proteins – at different times, in response to various factors, and in different parts of the body. These are the control and regulation elements, and there are various different types.
“The rest of our genome is leftover evolutionary material, parts of the genome that have undergone losses or gains in the DNA code,” Dr Lunter said.
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Rands CM et al. 2014. 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genetics 10 (7): e1004525; doi: 10.1371/journal.pgen.1004525
