Gene ‘switches’ are what really make humans tick

A landmark re-analysis of the human genome has found that our DNA contains millions of chemical switches that control our genes. It’s a finding that is set to revolutionise our understanding of human genetics and efforts to make new drugs based on our genes.

What has staggered scientists is the complexity of the gene regulation system – the number of switches far outnumbers the 20 thousand or so genes they control.

“There are way, way more switches than we ever thought possible – an insane number of switches,” said Dr Ewan Birney, of the European Bioinformatics Institute in Cambridge, who coordinated the 10-year international project.

What makes us tick is how we switch our genes on and off. Professor Tim Spector, King’s College London.

The basic units of our genome – the genes – code for proteins. These are the chemical components from which things in our body are made, from hair to hormones. DNA coding for genes makes up less than 2 per cent of our genome.

Scientists have known for a while that DNA contained extra code which switches genes on or off – helping determine why a hair cell makes hair and a liver cell breaks down alcohol. But the rest of the genome, more than 90 per cent of it, was thought to be junk – apparently useless genetic clutter left over from millions of years of evolution.

Fundamental shift

But the new study called ENCODE, published tomorrow in the science journal Nature, found that 80 per cent of that “junk” has some biochemical function at any one time in one particular cell or other in our body.

It’s a fundamental shift in thinking about how our DNA works, but it could also have more immediate implications for biomedical science. The study implicates gene switches – not genes themselves – in at least 400 diseases.

The ENCODE study reveals Crohn’s disease, type 1 diabetes, rheumatoid arthritis all have their origins in parts of our genome that don’t contain actual genes. Understanding which switches are affected, and how they can be turned on or off again, could result in new treatments for the conditions.

Nature versus nurture

The sheer number of gene switches also has major implications for the emerging field of “epigenetics.”

Epigenetics explains why identical twins – which share an identical set of genes – can have different coloured eyes, or one suffer a disease and the other not. Because external factors can trip these genetic switches, their genes can be expressed in different ways.

It’s becoming clear that factors that act on our genes can be as important as the genes themselves for determining who we are.

“Genetic switches show us that the old idea of nature versus nurture is no longer valid. The two are interchangeable and we’re all a mixture of both.” said Professor Tim Spector, a genetic epidemiologist at King’s College London.

“Genes do a great job of staying stable and reproducing over generations, but what makes us tick is how we switch our genes on and off.”

Some of the newly discovered sequences seem to be master switches, controlling large numbers of other genes. Others may switch on and off other switches. Others may have duplicate functions.

The fundamental question now, is why we have evolved to have so many genetic switches and whether all of them are crucial to our existence.