Spontaneous mutation at the mtr locus in neurospora: the molecular spectrum in wild-type and a mutator strain.
Sequence analysis of 34 mtr mutations has yielded the first molecular spectrum of spontaneous mutants in Neurospora crassa. The great majority of the mutations are base substitutions (48%) or deletions (35%). In addition, sequence analysis of the entire mtr region, including the 1472-base pair open reading frame and 1205 base pairs of flanking DNA, was performed in both the Oak Ridge and Mauriceville strains of Neurospora, which are known to be divergent at the DNA level. Sixteen sequence differences between these two strains have been found in the mtr region, with 13 of these in DNA flanking the open reading frame. The differences consisted of base substitutions and small frameshifts at monotonic runs. This set of sequence differences has allowed a comparison of mutations in unselected DNA to those mutations that produce a phenotypic signal. We have isolated a mutator strain (mut-1) of Neurospora in which the spontaneous mutation rate at various loci is as much as 80-fold higher than in the non-mutator (wild type). Twenty-one mtr mutations in the mutator background have been sequenced and compared to the non-mutator spectrum, revealing a striking increase in -1 frameshift mutations. These frameshifts occur exclusively within or adjacent to monotonic runs and can be explained by small slippage events during DNA replication. This argues for a role of the mut-1 gene in this process.
Dillon
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Department of Genetics, University of Washington, Seattle 98195.
Stadler
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D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral; D001483:Base Sequence; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D005799:Genes, Dominant; D005800:Genes, Fungal; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics*; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013045:Species Specificity
D026921:Amino Acid Transport Systems, Neutral; D004271:DNA, Fungal; D005656:Fungal Proteins; D008565:Membrane Proteins