The Perkins Lab -- Neurospora Genetics and Biology
Department of Biological Sciences, Stanford University

History of the Lab

Classic genetic analysis of Neurospora crassa over many years, much of it in our lab, led to the recognition and mapping of about 1000 genes and 350 rearrangements in the seven chromosomes (Perkins et al. 2001, Perkins 1997). The Neurospora genome has now been sequenced, revealing 9,000 additional open reading frames, and the function of these is being investigated by a consortium of other labs. Annotation is proceeding and >1400 named genes have been placed on the physical map (see Links).

We have been especially interested in the sexual phase of the Neurospora life cycle. Meiosis, postmeiotic mitoses, and ascospore formation take place in a single giant cell, the ascus, without partitioning by crosswall formation. Chromosomes, nuclei, and organelles are greatly enlarged during ascus development, making it ideal for cytological observations (e.g., Raju 1980, 1992, Raju and Perkins 1994, Perkins and Barry 1977). Special attention has been paid to N. tetrasperma, a species in which ascus development has been evolutionarily reprogrammed to produce four self-fertile heterokaryotic ascospores rather than the eight self-sterile monokaryotic haploid ascospores of other Neurospora species (Raju and Perkins 1994, Raju and Perkins 1991).

Cytogenetic studies of chromosome rearrangements revealed an abundance of insertional and terminal rearrangements. When each of these is crossed by normal sequence, meiotic recombination produces a class of partial diploid progeny that contain duplicated segments of defined content (Perkins 1974, Perkins and Barry 1977, Perkins 1997). Duplications obtained in this way have been used to study dosage and dominance, gene order (Perkins 1986), inactivation of genes by repeat induced point mutation (Perkins et al. 1997), and suppression of meiotic silencing by unpaired DNA (Shiu et al. 2001).

Studies of Neurospora from wild populations, initiated by us in 1968, have resulted in a collection of ~5000 cultures from around the world (Turner and Perkins 2001, Jacobson et al. 2004, 2006). These strains have provided a wealth of information on genetic polymorphisms, species recognition, and ecology, and have revealed the existence of 'Spore killer' haplotypes, which show meiotic drive (Turner and Perkins 1979, Raju 1994, 2002). Our collection has provided material for creating evolutionary trees which clarify the phylogeny of Neurospora and related genera and reveal the existence of putative phylogenetic species within the currently recognized biological species (Dettman et al. 2003a, 2003b, 2006). For example, N. discreta (described by Perkins and Raju 1986), is now known to be a species complex with as much genetic diversity and as wide a geographical distribution as all the other outbreeing Neurospora species combined. (Dettman et al. 2006, Jacobson et al. 2004, 2006).

Numerous challenging problems of sexual-phase development that could not be investigated because of technical limitations are no longer intractable, thanks to availability of the N. crassa genome sequence (Galagan et al. 2003) and the advent of new methods such as fluorescent tagging (Freitag et al. 2004). As an example, the reversible silencing of a given gene during ascus development can now be visualized by inserting ectopically a GFP-tagged copy of the gene, which remains unpaired during meiosis in heterozygous asci (Shiu et al. 2001, 2006, Freitag et al. 2004).

Current work in our laboratory (supported by NSF) continues a nearly unbroken line of Neurospora research at Stanford that began in 1941 with the classic experiments of George Beadle and Edward Tatum. Their use of Neurospora biochemical mutants opened the field of microbial genetics, led to the unification of genetics and biochemistry, and earned them the Nobel Prize in 1958 (See Horowitz 1991, Perkins 1992). Neurospora was the model that inspired initiation of genetic studies in E. coli and Saccharomyces in the 1940s, and it continues today as the model organism of choice for filamentous fungi (Davis and Perkins 2002).

For complete citations, please link to the Perkins Lab Publications and other useful Neurospora reviews, reference works, and compilations.

 

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