Genome of First Fungal Pathogen Unveiled

Geneticists at the Duke Institute for Genome Sciences and Policy (IGSP) and the University of Basel have unveiled the complete genome sequence of the pathogenic plant fungus Ashbya gossypii, which infects agricultural crops including cotton and citrus fruits in the tropics. The fungus has the smallest genome yet characterized among free-living eukaryotes. Eukaryotes are the single-celled and multicellular organisms that include fungi, plants and animals.

The team — led by Fred Dietrich, Ph.D., of the IGSP’s Center for Genome Technology, and Peter Phillipsen, Ph.D., of the University of Basel — reported its findings online in the March 4, 2004, Science Express, the online version of the journal Science. The work was completed with the funding and collaboration of Novartis (now Syngenta) in Research Triangle Park, N.C. The researchers have no financial ties to Novartis or Syngenta.

The sequencing of the fungal genome has already shed light on the evolution of Saccharomyces cerevisiae — the single-celled baker’s yeast that scientists rely on for the study of many basic questions in cell biology. Furthermore, understanding the infectious microbe’s genetic instructions might allow scientists to tease out the fundamental features responsible for some fungi’s ability to cause disease, the researchers said.

“We expect many similarities in function among all types of fungal pathogens — whether they infect plants or humans,” said Dietrich, first author of the study. “Understanding one will provide insight into fungal pathogens in general in terms of the forces that drive them.”

Ashbya’s stripped-down genome — containing just 9.2 million DNA base pairs, the fundamental building blocks of inheritance — will further simplify the task of deciphering genes and their functions, he added. The genomes of other important fungal pathogens can include as many as 200 million base pairs, more than 20 times that of the Ashbya genome. In comparison, the genetic blueprints contained in each human cell run to some 6 billion DNA base pairs.

The researchers first sequenced the Ashbya genome three times over in many segments and assembled those pieces into the sequences of the fungus’ seven chromosomes. The team then filled in any remaining gaps in the initial scaffold through additional sequencing. By comparing the sequence information to the yeast genome, the investigators identified the location of genes along the chromosomes.

Ashyba’s 9.2 million base pair genome encodes 4,718 protein coding genes, the team reported. The fungus shares more than 90 percent of those with yeast, with most occurring in a similar gene order.

Further comparison of the Ashbya and yeast genomes revealed 300 instances of sequence inversion or movement of a segment from one location to another since the divergence of the two species. The analysis also revealed two copies of the majority of Ashbya genes in the yeast genome, evidence that the evolution of S. cerevisiae included a whole genome duplication.

The fully annotated sequence will be made publicly available on GenBank, the National Institutes of Health genetic sequence database.

“This is the culmination of the work of many people over more than 10 years,” said Dietrich. “It’s very satisfying to finally be able to make this data public.” The support of Novartis hinged on an agreement that the data not be made public until the genome was complete, he said.

Collaborators on the project included Philippe Luedi, of Duke University Medical Center; Sylvia Voegeli, Sophie Brachat, Ph.D., Anita Lerch, Sabine Steiner, Ph.D., Christine Mohr, Ph.D., and Rainer Pohlmann, Ph.D., of the University of Basel; Krista Gates, Albert Flavier, Ph.D., and Thomas Gaffney, Ph.D., of Syngenta Biotechnology in Research Triangle Park; and Sangdun Choi, Ph.D., and Rod Wing, Ph.D., of Clemson University in South Carolina.

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