Photo via flickr by Nicholas_T
Scientists are finding that the blueprint for life is not all about genes. Recent research has revealed how much differences in non-coding DNA – stretches of the molecule that don’t produce proteins and used to be considered “junk” – shape who we are.
This ‘junk’ non-coding DNA, which makes up about 98 percent of the human genome, has been recognized in recent years to play a critical role in determining whether genes are active or not, and how much of a particular protein gets churned out.
Two teams have revealed dramatic differences between the non-coding ‘junk’ DNA of people whose genes are 99 percent the same. “We largely have the same sets of genes. It’s just how they’re regulated that makes them different,” says Michael Snyder, a geneticist at Stanford University in California who led a team of researchers with Jan Korbel, a geneticist at the European Molecular Biology Laboratory in Heidelberg, Germany.
Their study revealed dramatic differences between the non-coding ‘junk’ DNA of people whose genes are 99 per cent the same: five people of European descent, two others whose family origins lay in East Asia and three of west African origin. They found that transcription factors – proteins that attach to stretches of non-coding ‘junk’ DNA and affect how nearby genes make proteins – act at very different locations on the genomes of different people.
Humans have hundreds of different transcription factors, but Synder’s team focused on two that are known to be particularly promiscuous about where they attach to the genome: a protein involved in immune response, NF-kappa-B, and another that helps convert DNA to RNA, called Pol-II.
Snyder’s team didn’t study what effect these differences have, but he notes that points on the genome where transcription factor binding differed between people tended to be near genes implicated in schizophrenia, diabetes, rheumatoid arthritis and other ailments. He suggests, therefore, that these differences in transcription factor binding may affect disease risk.
To find out what causes transcription factors to work differently in different people, a team led by Ewan Birney, a geneticist at the European Bioinformatics Institute in Cambridge, UK, performed a similar analysis to Korbel’s team, except they compared cells from two families, each with a mother, father and two children.
This detail led them to conclude that inherited non-coding DNA sequences – not mutations in genes – may drive the lion’s share of differences in where transcription factors attach.
Kelly Frazer, a genomicist at the University of California, San Diego, says the new studies help explain why many common mutations linked to diseases are located so far from any gene. For instance, a certain mutation that increases the risk of heart attack by 60 per cent is not close to a gene.
She also suggests that by homing in on non-coding ‘junk’ DNA, researchers could begin to unravel what truly makes people different. “I think these two papers are the beginning of a field that’s going to be growing rapidly in the next few years,” she says.