Whitehead/MIT Genome Center Researchers Assemble Draft Sequence of Aspergillus nidulans

CAMBRIDGE, Mass. — The Whitehead Institute/MIT Center for Genome Research this week announced the public release of a high quality draft genome sequence of Aspergillus nidulans, a mold, or filamentous fungus commonly used in laboratory research to study important questions in genetics and cell biology. A. nidulans also is a close relative of a family of fungi that cause allergies in some individuals and life-threatening, opportunistic infections in patients with weakened immune systems. The A. nidulans sequence is freely available at http://www-genome.wi.mit.edu/annotation/fungi/aspergillus/.

Availability of this sequence represents a significant step for biomedical research because it provides a key tool to better understand the molecular workings of a suite of related molds or fungi that have medical, agricultural, and biotechnology implications.

"A. nidulans sequence is expected to be a Rosetta stone, the key, to understanding a large group of closely related fungi of great medical, commercial and evolutionary importance. These include organisms that make penicillin, citric acid, soy sauce, sake, and cholesterol lowering drugs," says Dr. Ron Morris of the Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey.

The sequencing of Aspergillus nidulans represents the first of a number of fungal sequencing projects supported by the National Human Genome Research Institute as part of the Fungal Genome Initiative, a comprehensive fungal sequencing program aimed at generating high-quality sequence for organisms spanning the fungal kingdom.

The sequencing of Aspergillus nidulans represents the first of a number of fungal sequencing projects supported by the National Human Genome Research Institute as part of the Fungal Genome Initiative, a comprehensive fungal sequencing program aimed at generating high-quality sequence for organisms spanning the fungal kingdom.

A. nidulans is a critical model system in genetics and cell biology. Unlike other Aspergilli, which are asexual, A. nidulans has a well-characterized, conventional genetic system, making it easier for scientists to study the role and function of genes. In addition, when genes from other Aspergilli as well as some genes from mammalian species are inserted into A nidulans, they can function in A. nidulans, allowing researchers to study genes of fungi with medical and other applications.

In addition to studying the A. nidulans genome, the Whitehead Institute/MIT Center for Genome Research and fungal biologists are especially excited about using comparative genomics to find insights into 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 sequences, we can understand the genes of A. nidulans better through comparison of the sequence to that of the other fungi being sequenced at the Center," says Bruce Birren, Director of the Sequencing Center at the Whitehead Institute.

The genome sequence was produced and assembled at the Whitehead Institute/MIT Center for Genome research, in collaboration with Monsanto Company. The genome was sequenced using the Whole Genome Shotgun approach, in which sequence from the entire genome is generated and reassembled by recognizing identical segments using the ARACHNE assembler, a sequence assembly program developed at the Whitehead Institute/MIT Genome Center.

The A. nidulans genome is approximately 31 million base pairs in size. The draft sequence shows the order of the DNA chemical bases A, T, C, and G along the fungus's eight chromosomes. It includes more than 95 percent of the genome with long, continuous stretches of overlapping DNA and represents 13-fold coverage of the genome. This means that the location of every base, or DNA letter, in the A. nidulans genome was determined an average of 13 times, a frequency that ensures a high degree of accuracy. Monsanto contributed 3X shotgun sequence, which has been publicly available on the Whitehead Institute/MIT Genome Center website since January 2003.

"Monsanto is proud to share this information with the Whitehead Institute/MIT Center for Genome Research," says Monsanto Genomics Lead Tom Adams. "We chose to collaborate with the Whitehead Institute/MIT Genome Center in order to enhance results from their NSF-funded Aspergillus nidulans genome sequencing project. We're very excited about the potential benefits that this project may yield for the agricultural, medical and biotechnology industries."

Currently, approximately 40 laboratories worldwide focus on the genetics and molecular biology of A. nidulans. Nine of these laboratories—representing the United States, Australia, England, France, and Germany—are members of the Fungal Genome Initiative steering group to promote sequencing and annotation of the A. nidulans genome.

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.