It turns out that “junk DNA”, once thought to comprise most of the genetic material packed into our cells, isn’t junk. Instead, it plays a complicated — and still shadowy — role in regulating our genes.
That’s the essential insight of a five-year project to study the 98 percent of the human genome that is not, strictly speaking, genes. It now appears that more than three-quarters of our DNA is active at some point in our lives.
“This concept of ‘junk DNA’ is really not accurate. It is an outdated metaphor to explain our genome,” said Richard Myers, one of the leaders of the 400-scientist Encyclopedia of DNA Elements Project, nicknamed Encode.
“The genome is just alive with stuff. We just really didn’t realize that before,” said Ewan Birney of the European Bioinformatics Institute in England.
The new insights are contained in six papers published Wednesday in the journal Nature. More than 20 related papers from Encode are appearing elsewhere.
The human genome consists of about 3 billion DNA “letters” strung one to another in 46 chains called chromosomes. Specific stretches of those letters (whose formal name is “nucleotides”) carry the instructions for making specific proteins. Those proteins, in turn, build the cells and tissues of living organisms.
The Human Genome Project, which identified the correct linear sequence of those letters, revealed that human cells contain only about 21,000 genes — far fewer than most biologists predicted. Furthermore, those genes took up only 2 percent of the cell’s DNA. The new research helps explain how so few genes can create an organism as complex as a human being.
The answer is that regulating genes — turning them on and off, adjusting their output, manipulating their timing, coordinating their activity with other genes — is where most of the action is.
The importance and subtlety of gene regulation is not a new idea. Nor is the idea that parts of the genome once thought to be “junk” may have some use. What the Encode findings reveal is the magnitude of the regulation.
It now appears that at least 4 million sections of the genome are involved in manipulating the activity of genes. Those sections act like switches in a wiring diagram, creating an almost infinite number of circuits.
“There is a modest number of genes and an immense number of elements that choreograph how those genes are used,” said Eric D. Green, director of the National Human Genome Research Institute, the federal agency that paid for the research.
The details of those interactions are still largely mysterious. The Encode project found, counted and compiled the stretches of DNA that for various reasons show evidence of biological activity. But exactly what they do in most cases isn’t yet known.
“What I am sure of is that this is the science for this century,” Birney said. “In this century we will be working out how humans are made from this instruction manual.”
The findings will be particularly useful in interpreting “genome-wide association studies” (GWAS).
In them, the genomes of people with a specific disease — Type 2 diabetes, coronary atherosclerosis, rheumatoid arthritis — are sequenced and compared with the genomes of people without the disease. In most cases, a dozen or more small changes in DNA sequence are found more often in the people with the disease than those without it.
Sometimes the reasons are obvious. People with at risk for heart attacks may have certain small changes in proteins involved in cholesterol metabolism or the construction of blood vessels. But often these DNA “variants” are in perplexing regions of the genome, far from the gene for the enzyme or protein involved in the disease.
The researchers suspect that 10 times as many of those risk variants occur in the regulatory “switches” as in the genes themselves.
That’s the essential insight of a five-year project to study the 98 percent of the human genome that is not, strictly speaking, genes. It now appears that more than three-quarters of our DNA is active at some point in our lives.
“This concept of ‘junk DNA’ is really not accurate. It is an outdated metaphor to explain our genome,” said Richard Myers, one of the leaders of the 400-scientist Encyclopedia of DNA Elements Project, nicknamed Encode.
“The genome is just alive with stuff. We just really didn’t realize that before,” said Ewan Birney of the European Bioinformatics Institute in England.
The new insights are contained in six papers published Wednesday in the journal Nature. More than 20 related papers from Encode are appearing elsewhere.
The human genome consists of about 3 billion DNA “letters” strung one to another in 46 chains called chromosomes. Specific stretches of those letters (whose formal name is “nucleotides”) carry the instructions for making specific proteins. Those proteins, in turn, build the cells and tissues of living organisms.
The Human Genome Project, which identified the correct linear sequence of those letters, revealed that human cells contain only about 21,000 genes — far fewer than most biologists predicted. Furthermore, those genes took up only 2 percent of the cell’s DNA. The new research helps explain how so few genes can create an organism as complex as a human being.
The answer is that regulating genes — turning them on and off, adjusting their output, manipulating their timing, coordinating their activity with other genes — is where most of the action is.
The importance and subtlety of gene regulation is not a new idea. Nor is the idea that parts of the genome once thought to be “junk” may have some use. What the Encode findings reveal is the magnitude of the regulation.
It now appears that at least 4 million sections of the genome are involved in manipulating the activity of genes. Those sections act like switches in a wiring diagram, creating an almost infinite number of circuits.
“There is a modest number of genes and an immense number of elements that choreograph how those genes are used,” said Eric D. Green, director of the National Human Genome Research Institute, the federal agency that paid for the research.
The details of those interactions are still largely mysterious. The Encode project found, counted and compiled the stretches of DNA that for various reasons show evidence of biological activity. But exactly what they do in most cases isn’t yet known.
“What I am sure of is that this is the science for this century,” Birney said. “In this century we will be working out how humans are made from this instruction manual.”
The findings will be particularly useful in interpreting “genome-wide association studies” (GWAS).
In them, the genomes of people with a specific disease — Type 2 diabetes, coronary atherosclerosis, rheumatoid arthritis — are sequenced and compared with the genomes of people without the disease. In most cases, a dozen or more small changes in DNA sequence are found more often in the people with the disease than those without it.
Sometimes the reasons are obvious. People with at risk for heart attacks may have certain small changes in proteins involved in cholesterol metabolism or the construction of blood vessels. But often these DNA “variants” are in perplexing regions of the genome, far from the gene for the enzyme or protein involved in the disease.
The researchers suspect that 10 times as many of those risk variants occur in the regulatory “switches” as in the genes themselves.