Genomics in Neurospora crassa: From One-Gene- One-Enzyme to 10,000 Genes

Neurospora crassa was the central organism in the development of biochemical genetics, providing a model system that established the relationship between genes and enzymes; it remains the best-studied filamentous fungus. This review focuses on the impact that the recent publication of a high-quality draft sequence of the N. crassa genome will have upon efforts to understand the biology of the filamentous fungi. Although several fungal genomes have been sequenced, annotated, and published, the organisms that have been examined are yeasts with relatively small genomes. In sharp contrast, N. crassa contains about 10,000 protein-coding genes, approximately twice as many genes as the yeasts and only slightly fewer than the invertebrate animals. Analysis of this gene set suggests that several different processes have led to the differences in gene content between N. crassa and the yeasts. Evidence for the loss of genes in the yeasts and the acquisition of novel genes in Neurospora lineage is described, as well as details regarding the biological processes that have led to these changes. Analyses of the N. crassa genome sequence revealed the widest array of genome defense mechanisms known for any organism, and one of these defense mechanisms (RIP) appears to have blocked the productive duplication of genes. Since gene duplication is the most common pathway for the origin of novel genes, it seems likely that N. crassa will provide an excellent model system for understanding alternative ways in which novel genes arise. A number of unexpected genes were identified when the complete genome sequence was analyzed, indicating that N. crassa produces secondary metabolites, shares apparent "pathogenicity" genes with plant pathogens, and responds to environmental cues such as light in novel ways. The genome sequence for N. crassa is the first exciting step toward a detailed understanding of the biology of filamentous fungi, and it will allow fungal biologists to establish which features of the filamentous fungi are shared with nonfungal organisms and which features are unique.