Chromosomal Loci of Neurospora crassa

DAVID D. PERKINS,(1)* ALAN RADFORD,(2) DOROTHY NEWMEYER,(1) and MONIKA BJORKMAN(1) Department of Biological Sciences, Stanford University, Stanford, California 94305(1) and Department of Genetics, The University of Leeds, Leeds LS2 9JT, England(2)


In this article we bring together information on the phenotypes, genetic characteristics, and map locations of all the known Mendelian gene loci of Neurospora crassa and on other chromosomal landmarks such as centromeres, tips, and the nucleolus organizer. Over 500 loci are included. Linkage maps have been revised and augmented. If sites of gene action are known, they are indicated in figures that show biosynthetic or catabolic pathways. Information on wild-type enzymes is included only where necessary to explain the mutant phenotypes. The text is concerned primarily with the organization and function of each locus and only secondarily with allelic variation or properties that distinguish specific alleles. Chromosome rearrangements are not considered except when mapping or analysis of loci depends upon rearrangement break points. (See reference 808 for a review of rearrangements.) Mutations in the mitochondrial genome are not considered except as necessary for describing nuclear genes that interact with mitochondrial mutations. (See reference 394 for a review of mitochondrial genetics and reference 206 for a map of the Neurospora mitochondrial genome.)

For a brief general introduction to the biology, genetics, and cytology of Neurospora, see the opening sections of reference 808, where references to the most useful sources of more detailed information may be found.

Neurospora was named and described 55 years ago by Shear and Dodge (978), who showed that mating type is determined by a single pair of alleles that show 4:4 segregation among unordered asci which were shot from the perithecia. Morphological differences of sponta- neous origin were soon discovered and shown by Dodge to segregate in Mendelian fashion. The linear array of ascospores in the ascus was shown cytologically by M S. Wilcox to reflect events in meiosis, and genes were shown by Wilcox and by Dodge to segregate sometimes at the first and sometimes at the second division of meiosis. C. C. Lindegren proposed that second division segregations, as reflected in ascospore order, measured the frequency of crossing-over in the segment between a gene locus and its centromere. Lindegren discovered linked genes and constructed the first linkage maps (eight genes and the centromeres in two linkage groups) (609-611, 613). For references and accounts of the early Neurospora work, see reference 808 and Neurospora Newsletter (volume 20, 1973).

The predominantly auxotrophic mutants obtained by G. W. Beadle, E. L. Tatum, and their associates, beginning in 1941, were used to construct more complete maps. Six linkage groups were known by 1949 (482), and the seventh was soon added (874).

B. McClintock and J. R. Singleton showed in the 1940s that chromosome morphology and behavior during meiosis and mitosis in the ascus resemble those in higher eucaryotes and that they can be studied cytologically by the methods of plant cytogenetics, using light microscopy. The first genetic evidence of chromosome rearrangements was obtained in this period (see reference 482), and translocations were confirmed and described cytologically (656, 987).

The discovery of biochemical mutants in Neurospora in 1941 (67) led to the explosive development of biochemical genetics and molecular biology. Although many problems could be attacked more readily by using bacteria and viruses, N. crassa continued to be used as a eucaryotic model, and a succession of fundamental contributions were made using Neurospora. Auxotrophic mutants were used to elucidate biosynthetic pathways (e.g., reference 1010). Complementaton between alleles was demonstrated both in vivo and in vitro (344, 393 1157). Temperature-sensitive conditional mutants that were irreparable by supplementation were obtained (481, 484). Gene conversion was proved (686) and its important characteristics were delineated (e.g., references 143, 362, 720, 907 and 1015). Meiotic recombination within genes shown to be polarized (720). Genes that regulate the frequency of locally specific recombination events within and between other genes were discovered and characterized (see references 167 and 170). The complete meiotic karyotype was reconstructed in three dimensions for the synaptonemal complex, with its associated recombination nodules (see reference 396). Genetic polymorphisms were shown to be abun- dant in natural populations of Neurospora-not a foregone conclusion for a vegetatively haploid microorganism (601. 730, 1002). Electrophoretic and other variants from wild- collected strains proved a valuable adjunct to the mutants obtained from laboratory strains by conventional means (820) (for examples, see entries below for leu-5, het, ars. mig, ss, and pts).

An abundance of evidence from Neurospora established the basic similarity of genetic mechanisms in fungi, with their small DNA genomes, to those of higher eucaryotes. This applies to meiosis, crossing-over and interference, gene conversion and intragenic recombination, chromosome rearrangements, genome organization, chromosome composition and structure, and the presence of systems of meiotic drive (see references 571, 791, 808 and references therein, and 1092). In the realm of gene action, genetic and biochemical studies with Neurospora have contributed basic information on biosynthetic pathways, gene-enzyme relations (see reference 343), regulation (237, 427, 642, 665), transport (921, 1150, 1151), circadian rhythms (328), and the interplay between chromosomal and mitochondrial genomes in specifying organelle structure (see reference 394).

These and other investigations with Neurospora have resulted in a vast literature, gathered in bibliographies (36-38, 373); the first two of' these have been thoroughly indexed by subject. The present review brings together the widely scattered information on genetic properties, phenotypes,. and map relationships of all the known genes.

Usage in this review reflects current practice of Neurospora workers and of the Fungal Genetic Stock Center (FGSC) (43, 44, 52, 807). The basic Neurospora conventions antedate bacterial genetic nomenclature and follow those of Drosophila more closely. Gene symbols are written in lower-case italics (e.g., nmr) unless the mutant allele is known to be dominant; the first letter is then capitalized (e.g., Ban). (Mating type alleles, A and a, are an exception.) A symbol without superscript is used to represent the mutant allele. The same symbol with a superscript plus (+) designates the wild-type allele. Multiple alleles or alleles differing in resistance or sensitivity, or allelic series having no definitive wild type, may be distinguished by other superscripts, e.g., cyh-1R, cyh-1S, het-60R, het-6PA, TL, TS.

Although the basic letter symbols for many auxotrophic loci are the same as for those of bacteria, locus symbols for Neurospora often consist of fewer than three letters. Nonallelic "mimic" loci having the same descriptive letter symbol are distinguished from one another by numbers following the symbol rather than by capital letters as for bacteria. A hyphen separates the distinguishing number from the common letter symbol (e.g., ilv-2, ilv-3).

Allelic mutations bear identical locus symbols and numbers. Each new mutation is assigned a unique allele number (often called an isolation number) to distinguish it from all allelic mutations of independent origin. (Allele numbers are commonly prefixed by letters indicating the laboratory of origin.) Allele numbers are not usually displayed with the gene symbol, except when necessitated by the use of several alleles, when it is included in parentheses after the full locus symbol, e.g., pyr-3 (KS43), or when a new mutant gene has not yet been assigned a locus number pending tests for allelism with similar genes at previously established loci. In the latter situation, a mutant gene is temporarily designated by an appropriate letter symbol followed immediately by the allele number in parentheses, e.g., ilv(STL6). When new locus symbols, locus numbers, and allele number prefixes are to be assigned, it is advisable to consult other workers and the latest FGSC stock list to avoid duplication. Regulatory genes have usually been given the same basic letter symbol as the structural genes they regulate (e.g., nit-2, leu-3, cys-3), but this is not always true (e.g., pcon, pgov, scon, ty). Suppressors are symbolized by "su" followed immediately by the symbol of the suppressed gene in parentheses; locus numbers of nonallelic suppressors of the same gene follow the parentheses [e.g., su(met-7)-1, su(met-7)-2]. As for Drosophila, "su+" designates the wild type, and "su" designates the mutant suppressor allele. For allele-specific suppressors, the allele number is included as a superscript of the locus symbol, e.g., su(trp"td201)-1. Conventions are similar for supersuppressors (nonsense suppressors), with the basic symbol ssu.

A few symbols that were previously ambiguous or imprecise have been revised here, with the agreement of the investigators concerned.

Alleles at several gene loci originated in other Neurospora species and have been introgressed into N. crassa. Those species capable of gene exchange by way of sexual crosses all appear to be similar in chromosome sequence (808; E. G. Barry, personal communication). Introgressed markers have, therefore, been treated as though they had arisen as mutations within N. crassa.

Genetic linkage groups are designated by Roman numerals, and cytologically defined chromosomes are designated by Arabic numbers. Linkage group arms are conventionally designated as right (R) and left (L). Heterokaryons are represented by genotypes of the component nuclei enclosed in parentheses, e.g., (al-2 arg-6 A + arg-1 al-1 A). Mitochondrial variants are designated by italicized symbols enclosed in brackets, e.g., [mi-3]. Chromosome rearrangements include translocations (symbol T), inversions (In), transpositions within the same chromosome (Tp), and duplications (Dp). This symbol is followed by the linkage groups involved, in parentheses, and an identification number. With reciprocal translocations, the linkage groups are separated by a semicolon (e.g., T(I;II)4637, a reciprocal interchange between linkage groups I and II). With insertional or terminal rearrangements, the linkage groups are separated by an arrow indicating which is the donor and which the recipient of the transferred segment [e.g., T(I->II)39311, wherein a segment of linkage group I is inserted into II].

For more explicit recommendations regarding genetic nomenclature, see the references mentioned at the beginning of this section.