Diverse interactions mediate asymmetric incompatibility by the het-6 supergene complex in Neurospora crassa

Heterokaryon incompatibility (HI) in filamentous fungi is a form of nonself recognition that operates during the vegetative phase of the life cycle. One HI gene complex in Neurospora crassa, the het-6 locus, comprises two incompatibility genes, het-6 and un-24, each having two allelic variants, Oak Ridge (OR) and Panama (PA). The un-24 gene also encodes the large subunit of ribonucleotide reductase while het-6 appears to be a member of a repetitive gene family with no other known function aside from HI. These two genes are in severe linkage disequilibrium such that only un-24(OR)het-6(OR) and un-24(PA)het-6(PA) haplotypes occur in nature. In this study we unravel several genetic interactions that govern the HI functions of this gene complex. We use novel un-24(PA)het-6(OR) strains and het-6 deletion strains to demonstrate that nonallelic interactions occur between un-24 and het-6 and reveal an allelic incompatibility interaction between the OR and PA forms of un-24 that is asymmetrically enhanced by the presence of het-6(OR) or het-6(PA). We also show how two allelic forms of vib-1, a suppressor of het-c- and mat-associated incompatibility, differentially act as recessive suppressors of HI associated with nonallelic interactions between un-24(PA) and het-6(OR). In contrast, vib-1 is a dominant suppressor of HI associated with allelic differences at un-24 and a dominant partial suppressor of the un-24(OR) and het-6(PA) nonallelic interaction. The range of suppressor activities is largely explained by an interesting differential effect on het-6(OR) and het-6(PA) transcript levels by VIB-1.