‘Junk DNA’ concept debunked by new analysis of human genome

Most of a person’s genetic risk for common diseases such as diabetes, asthma and hardening of the arteries appears to lie in the shadowy part of the human genome once disparaged as “junk DNA.”

Indeed, the vast majority of human DNA seems to be involved in maintaining individuals’ well being — a view radically at odds with what biologists have thought for the past three decades.

Those are among the key insights of a nine-year project to study the 97 percent of the human genome that’s not, strictly speaking, made up of genes.

The Encyclopedia of DNA Elements Project, nicknamed Encode, is the most comprehensive effort to make sense of the totality of the 3 billion nucleotides that are packed into our cells.

The project’s chief discovery is the identification of about 4 million sites involved in regulating gene activity. Previously, only a few thousand such sites were known. In all, at least 80 percent of the genome appears to be active at least sometime in our lives. Further research may reveal that virtually all of the DNA passed down from generation to generation has been kept for a reason.

“This concept of ‘junk DNA’ is really not accurate. It is an outdated metaphor,” said Richard Myers of the HudsonAlpha Institute for Biotechnology in Alabama.

Myers is one of the leaders of the project, involving more than 400 scientists at 32 institutions.

Another Encode leader, Ewan Birney of the European Bioinformatics Institute in Britain, said: “The genome is just alive with stuff. We just really didn’t realize that beforehand.”

“What I am sure of is that this is the science for this century,” he said. “In this century, we will be working out how humans are made from this instruction manual.”

The new insights are contained in six papers published Wednesday in the journal Nature. More than 20 related papers are appearing elsewhere.

The human genome consists of about 3 billion nucleotides — the “letters” — strung one to another in chains. Specific stretches of those nucleotides carry the instructions for making specific proteins. The proteins, in turn, become the blocks of tissues and the enzymes, hormones and carrier molecules that do most of the cell’s work.

The Human Genome Project identified the correct linear sequence of those letters. At its completion in 2003, only 21,000 genes had been identified — far fewer than most biologists predicted. Furthermore, the genes constituted only 3 percent of the cell’s DNA, leaving biologists to wonder about what function, if any, the remaining 97 percent had. Encode was created to try to answer that question.

“Back then we got the book, but we didn’t know how to read it,” said Elise Feingold of the National Human Genome Research Institute, the federal agency that provided about $200 million for the project.

The new research helps explain how so few genes can create an organism as complex as a human being. The answer is that regulation — turning genes on and off at different times in different types of cells, adjusting a gene’s output and coordinating its activities with other genes — is where most of the action is.