Apr. 28, 2003 ARLINGTON, Va. -- With more than 10,000 genes amid DNA strands of nearly 40 million base pairs, the first genome of a filamentous fungus has been sequenced through the cooperative efforts of a community of more than 70 scientists, culminating a two-year, $5 million effort supported by the National Science Foundation. The work is reported in this week's issue of Nature, which celebrates the 50th anniversary of that journal's publication of the structure of DNA.
At the center of this latest genetics achievement is a filamentous fungus, a bread mold, a life form easily overlooked in the shadow of the Human Genome Project. To biologists, however, it is Neurospora crassa, an organism of historic and enduring value as a model organism.
More than a decade before the structure of DNA was determined, two biologists focusing on Neurospora as a model genetic organism first established that genes provide the information for the creation of proteins. For their "one gene, one enzyme" hypothesis linking genes to biochemical function, the two scientists-- George Wells Beadle and Edward Lawri Tatum--received the Nobel Prize in 1941.
"The legacy of over 70 years of research, coupled with the availability of molecular and genetic tools, offers enormous potential for continued discovery," write the authors of the current Nature article. They call their genome sequence a "high quality draft," covering pretty much all but the 2 to 3 percent in "unusual genomic regions…that cannot be assembled readily with available techniques."
An organism's genome consists of the entire genetic code held in its DNA. With more than 5000 papers on Neurospora published in the past 30 years, having the genome now allows many previous biological studies to be seen in a new light.
Though initially billed as "not a research project, but a high throughput production effort," the sequencing effort nevertheless yielded new insights into light sensitivity, fungal growth, circadian rhythms, calcium-release mechanisms, and other basic cellular phenomena.
It also shed new light on the production of compounds called "secondary metabolites," such as pigments, antibiotics and toxins. The fungal world, with more than 250,000 species and inhabitants in every ecosystem on earth, produces a vast array of these small, bioactive compounds.
Fungi--slime molds and mushrooms among them--are used for food and for the production of industrial chemicals and enzymes. They also rot wood, damage fabric, obscure optics and, as pathogens, injure animals and plants.
Charting Neurospora's DNA sequence allowed scientists to examine a curious genetic mechanism unique to fungi known as repeat induced point mutation, or RIP. First discovered in Neurospora in the 1980s, the RIP process detects and mutates whole sections of DNA where it finds a duplication in the DNA, a condition that otherwise often leads to the creation of new genes. The authors suggest that "RIP has a powerful impact in suppressing the creation of these new genes or partial genes" and it may have "virtually arrested" the further evolution of Neurospora.
According to Maryanna Henkart, director for NSF's Division of Molecular and Cellular Biology, the evolution of the Neurospora sequencing effort itself has been driven by a sense of community among those who study the mold.
The first genome project on Neurospora began in 1995 under a five year NSF grant to the University of New Mexico to improve research opportunities for minorities. It involved 36 students preparing and sequencing the DNA of some specific genes. Most were Hispanic or Native American. The authors of the project's first paper included 17 undergraduates, several of whom are now with leading genome institutes.
"In 2000, the greater Neurospora community mobilized to find a way to get the complete genome sequence done," said Henkart. Teamed with Bruce Birren of the Whitehead Institute at Massachusetts Institute of Technology, they submitted an ambitious, ultimately successful, proposal.
Begun in September 2000, the project released its first batch of sequence data on Feb. 14, 2001, with additional segments subsequently released.
By its completion, it had involved collaborators from more than 30 universities and research groups, representing more than 10 U.S. states and six countries.
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