Recurrent Locus-Specific Mutation Resulting From a Cryptic Ectopic Insertion in Neurospora

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Abstract
New mutations are found among ∼20% of progeny when one or both parents carry eas allele UCLA191 (easUCLA, 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, easUCLA-induced cya-8 mutations occur during nuclear proliferation prior to karyogamy. When only one parent is easUCLA, the new mutations arise exclusively in easUCLA 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 easUCLA allele is associated with a long paracentric inversion. A discontinuity is present in easUCLA DNA. The eas promoter is methylated in cya-8 progeny of easUCLA, 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.