title: Recurrent locus-specific mutation resulting from a cryptic ectopic insertion in Neurospora.
abstract: New mutations are found among approximately 20% of progeny when one or both parents carry eas allele UCLA191 (eas(UCLA), easily wettable, hydrophobin-deficient, linkage group II). The mutations inactivate the wild-type allele of cya-8 (cytochrome aa3 deficient, linkage group VII), resulting in thin, "transparent" mycelial growth. Other eas alleles fail to produce cya-8 mutant progeny. The recurrent cya-8 mutations are attributed to repeat-induced point mutation (RIP) resulting from a duplicated copy of cya-8+ that was inserted ectopically at eas when the UCLA191 mutation occurred. As expected for RIP, eas(UCLA)-induced cya-8 mutations occur during nuclear proliferation prior to karyogamy. When only one parent is eas(UCLA), the new mutations arise exclusively in eas(UCLA) nuclei. Mutation of cya-8 is suppressed when a long unlinked duplication is present. Stable cya-8 mutations are effectively eliminated in crosses homozygous for rid, a recessive suppressor of RIP. The eas(UCLA) allele is associated with a long paracentric inversion. A discontinuity is present in eas(UCLA) DNA. The eas promoter is methylated in cya-8 progeny of eas(UCLA), presumably by the spreading of methylation beyond the adjoining RIP-inactivated duplication. These findings support a model in which an ectopic insertion that created a mutation at the target site acts as a locus-specific mutator via RIP.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Perkins
authors.forename: Michael
authors.initials: M
authors.lastname: Freitag
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Pollard
authors.forename: Lori A
authors.initials: LA
authors.lastname: Bailey-Shrode
authors.forename: Eric U
authors.initials: EU
authors.lastname: Selker
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ebbole
mesh_terms: D000483:Alleles; D002467:Cell Nucleus / Q000378:metabolism; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003434:Crossing Over, Genetic; D004271:DNA, Fungal; D005306:Fertilization; D020440:Gene Duplication; D020868:Gene Silencing; D005800:Genes, Fungal; D008040:Genetic Linkage; D006579:Heterozygote; D006720:Homozygote; D008540:Meiosis; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D009491:Neurospora / Q000166:cytology / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D013172:Spores, Fungal / Q000235:genetics; D013489:Suppression, Genetic
chemical_list: D004271:DNA, Fungal