UW Today

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December 23, 2010

From tiny worms, scientists learn to read DNA instructions

UW Health Sciences/UW Medicine

Video: Dr. Bob Waterston talks about the roundworm genome

Read the Science article, “From Genomes to Regulatory Networks.”

The first-ever integrated analysis of the molecular processes that control genome function in an animal — in this case, the roundworm — has the potential to speed understanding of the molecular processes in human cells, according to a study in the Dec. 24 issue of Science authored by an international group of scientists that includes UW Medicine researchers.

UW genome scientist Dr. Bob Waterston began studying the roundworm genome in the 1990s as part of the Human Genome Project. Today, scientists are learning to read the DNA instructions contained in the roundworm genome.

UW genome scientist Dr. Bob Waterston began studying the roundworm genome in the 1990s as part of the Human Genome Project. Today, scientists are learning to read the DNA instructions contained in the roundworm genome.

Waterston is a member of the model organism ENCyclopedia Of DNA Elements (modENCODE) Consortium, the international group of scientists who authored the paper and are funded by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. A companion Science paper reports findings of a similar study in the fruit fly (Drosophila melanogaster), and more than a dozen companion modENCODE papers are published online in the journals Nature, Genome Research and Genome Biology.

The roundworm and the fruit fly genome sequences were initially sequenced alongside the Human Genome Project and are routinely compared to the human genome sequence in experiments that rely on millions of years of evolution. The authors found that particularly important stretches of DNA in the genome are “conserved,” or retained, throughout evolutionary history.

“The deep evolutionary connection between flies, worms and humans makes research in these model organisms highly relevant to human biology,” Waterston said.

An adult roundworm, magnified many times.

An adult roundworm, magnified many times.

“When we completed the worm genome sequence in 1998, we could only recognize the function of a fraction of the genome,” Waterston said. “These studies combine to reveal more than 80% of the functional elements – a dream come true.”

The researchers examined the organization and structure of DNA and its associated proteins, called chromatin, in the cells throughout the life stages of each organism. Strikingly, both groups — those studying the worm and those studying the fly — discovered specific chromatin signatures associated with the regulation of genes in their respective organism. Unique chromatin signatures were associated with distinct regions of the genome that either turn genes on or off.

“By correlating the chromatin signatures with the patterns of gene expression,” Waterson said, “we were able to predict the actions of the genome in different states, providing a powerful means for understanding how genomes work.”

An roundworm embryo. Specific genes are turned on and off during embryonic development to make body parts.

An roundworm embryo. Specific genes are turned on and off during embryonic development to make body parts.

Other authors are from Fred Hutchinson Cancer Research Center, Seattle, WA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Dana-Farber Cancer Institute, Boston, MA; European Molecular Biology Laboratory, Heidelberg, Germany; Harvard School of Public Health, Boston, MA; Lawrence Berkeley National Laboratory, Berkeley, CA; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; National Human Genome Research Institute, Bethesda, MD; New York University, New York City, NY; NimbleGen Systems, Madison, WI; Ontario Institute for Cancer Research, Canada; Sloan-Kettering Institute, New York, NY; Stanford University, Palo Alto, CA; State University of New York at Stonybrook; University of Toronto, Canada; University of California- Berkeley, University of California- San Diego, University of California- Santa Cruz; University of Cambridge, Cambridge, UK; University of Michigan, Ann Arbor, MI; University of North Carolina; Vanderbilt University, Nashville, TN; Weizmann Institute of Science, Rehovat, Israel; Yale University, New Haven CT.