Scientists Publish Draft Sequence and Analysis of Neurospora crassa

Cambridge, MA (April 24, 2003) -- The Whitehead Institute/MIT Center for Genome Research today announces the publication of a high-quality draft sequence of the Neurospora crassa genome - better known as common bread mold - together with an analysis describing insights gleaned from the sequence. The paper appears in the April 24 issue of the journal Nature.

"Neurospora is the most thoroughly and intensively studied of the filamentous fungi, a group of organisms including molds and mushrooms," says Matthew Sachs, collaborator and co-principal investigator from Oregon Health & Science University. "Obtaining its genetic blueprint is the single most important achievement for gaining a complete understanding of this organism's biology. It is also already proving to be extremely useful for understanding the biology of related fungi that are less well studied, and, perhaps surprisingly, for understanding 'higher' organisms such as animals."

Neurospora crassa

Like the fruit fly Drosophila melanogaster, Neurospora has served as a powerful laboratory model to study genetics and biological mechanisms for over 60 years. Availability of this genome sequence represents a significant step for biomedical research by providing a key tool for understanding the molecular workings of a related fungi with medical, agricultural, and biotechnology implications. Neurospora has close fungal relatives that cause animal disease such as athlete's foot and valley fever, or plant diseases that decimate staple crops such as rice, corn, and soy.

Among the findings in the Neurospora analysis is that the genome encodes about 10,000 protein-coding genes, far less than the estimated 30,000 that humans have, but comparable to that of the fruitfly. Neurospora has about twice as many protein-coding genes as the yeast Saccharomyces cerevisiae.

Neurospora has been extensively studied because although it is a simple organism, it shares many biological processes with more complex organisms. Like yeast, it has been an important model in the study of cell biology. However, because of its greater complexity, Neurospora is used to study processes not present in yeast such as circadian rhythms and complex signalling networks.

Additionally, Neurospora has the most genome defense mechanisms of any model eukaryote organism, including the unique fungal mechanism of repeat-induced point mutation (RIP) that appears to prevent the formation of new genes through gene duplication.

Neurospora is the flagship of fungal genome sequencing efforts, and the first filamentous fungus to be sequenced. The draft sequence was produced and assembled at the Whitehead Institute/MIT Center for Genome Research with funding from the National Science Foundation. The program was the result of a collaboration between the Genome Center and a broad community of neurospora researchers.

"This analysis project was a wonderful synergy between the sequencing and computational expertise of the Whitehead/MIT Genome Center and the extensive knowledge base and collaborative spirit of scientists that use Neurospora as an experimental organism," says Katherine Borkovich, author on the paper and professor at the University of California, Riverside. "Working together, we were able to explore this genome in a very accurate and comprehensive manner that has not before been seen in a genome sequence of this size."

The genome was sequenced using the Whole Genome Shotgun (WGS) approach. Sequence from the entire genome was generated and reassembled by recognizing identical segments using the ARACHNE assembler, a program developed at the Whitehead Institute/MIT Genome Center. The WGS method is standard for microbial genome sequencing, and has been successfully applied to the fruitfly and mouse. The Neurospora sequence is freely available at http://www-genome.wi.mit.edu/annotation/fungi/neurospora/. The sequence is still considered a draft because there are very small missing or ambiguous portions of the sequence. Efforts to finish are ongoing and the final genome sequence is expected by the end of this year.

Neurospora crassa image courtesy of N. B. Raju, Stanford University

The Neurospora genome is approximately 40 million base pairs in size and encodes roughly 10,000 proteins. The draft sequence shows the order of the DNA chemical bases A, T, C, and G along the fungus' seven chromosomes. It includes more than 95 percent of the genome with long, continuous stretches of overlapping DNA and represents 20-fold coverage of the genome. This means that the location of every base, or DNA letter, in the Neurospora genome was determined an average of 20 times, a frequency that ensures a high degree of accuracy.

"The Neurospora genome is extremely exciting from an evolutionary perspective as it will provide the opportunity to investigate new aspects of genome evolution," says James Galagan, lead author of the paper and scientist at the Whitehead Institute/MIT Center for Genome Research. "The analysis of the genome has provided many new insights into a variety of cellular processes, including genome defense and cell signaling, growth and differentiation."

In addition to studying the Neurospora genome, the Whitehead Institute/MIT Center for Genome Research and fungal biologists are especially excited about using comparative genomics to study the biology of fungi in general. "Just as we are learning a great deal about the human genome by comparing it to the mouse genome sequence, we can understand the genes of Neurospora better through comparison of the sequence to that of the other fungi being sequenced at the Genome Center," says Bruce Birren, Co-Director of the Sequencing Center at the Whitehead Institute.

Through a new Fungal Genome Initiative, the Genome Center is sequencing a broad spectrum of species across the fungal kingdom and will provide nine complete genomes this year. The genomes of Magnaporthe grisea and Aspergillus nidulans are already available at http://www-genome.wi.mit.edu/annotation.

The Whitehead Institute/MIT Center for Genome Research is an international leader in the field of genomics, the study of all of the genes in an organism and how they function together in health and disease. A flagship of the Human Genome Project, the Center today houses a broad range of thriving research programs combining structural genomics, medical and population genetics, and clinical medicine. The Center's annual budget is $80 million, and it employs 350 people, including scientists and medical researchers from Whitehead, MIT, and Harvard.

For more information, contact:
Lisa Marinelli, 617.252.1967