International research teams have junked the notion of "junk" DNA, reporting that at least 80% of the human genetic blueprint contains gene switches, once thought useless, that control the genes that make us healthy or sick.
Released Wednesday, the $288 million Encyclopedia of DNA Elements (ENCODE) project was funded by the federal National Human Genome Research Instituteover the last five years. It includes reports by 440 researchers from 32 labs worldwide. The project set out to explain the mystery behind one of the findings of the 2003 Human Genome Project, why only 2% of human genes seemed directly involved in the production of bone, blood, muscle and other tissues.
"The major lesson from ENCODE is how complex the human genome turns out to be, with this incredible choreography of switches that turn genes on and off," NHGRI chief Eric Green says. Those switches, also called transcription factors or "regulatory" genes, number more than 4 million so far, residing on stretches of DNA once thought of as junk.
Results show these regulatory genes turn on and off to control genes that produce bone, blood, insulin, muscle and other tissues. They also play a major role in disease. The effort is just a massive beginning stab at understanding the gene networks that let genes produce the proteins and other material that build human beings. Among the findings from the reports already:
•Rare diseases: The results show that variations in these regulatory genes, once thought of as junk, are responsible for most of the common ailments humans face, such as the gut ailment Crohn's disease. Scientists have also tried to find illnesses tied to mistakes in single genes, but the new results suggest that complex illnesses tied to these regulatory genes are five to 10 times more common than ones tied to mistakes in single genes, says Stanford University's Michael Snyder.
•Cancer: Among the 17 major types of cancer, each type repeatedly suffers from defects in 20 transcription factors, "over and over again," says genome scientist John Stamatoyannopoulos of the University of Washington School of Medicine in Seattle.
•Evolution: Color vision and nerve growth regulatory genes show evidence of recent evolution in humans.
The studies, released by the journals Nature, Science, Cell and others, reflect the results of more than 1,600 experiments on 180 different cell types to trace these gene networks, says Richard Myers of the HudsonAlpha Institute for Biotechnology in Huntsville, Ala. Understanding these networks of genetic switches will provide new targets for drugs aimed at the genes and for "personalized" medicine, Myers and other researchers suggested, where drugs tuned to a person's specific genetic makeup are given to both prevent and treat disease.
"We're going to have to shift to a broader kind of language beyond the word gene," to describe how gene switches work, says Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute. Although the ENCODE results suggest that at least 80% of "junk" DNA actually plays a role in controlling other genes, Birney believes that more likely nearly 100% of it will prove to have a purpose, and many more regulatory genes await discovery.
NHGRI has made available up to another $123 million in research funding for more ENCODE efforts in the next four years. "Our complete understanding of how the human genome works is far ahead of us," Green says.