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bioRxiv · 10.1101/2023.12.19.572315

het-B allorecognition in Podospora anserina is determined by pseudo-allelic interaction of genes encoding a HET and lectin fold domain protein and a PII-like protein

Clave, C.·Dheur, S.·Ament-Velasquez, S. L.·Granger-Farbos, A.·Saupe, S. J.
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Abstract

Filamentous fungi display allorecognition genes that trigger regulated cell death (RCD) when strains of unlike genotype fuse. Podospora anserina is one of several model species for the study of this allorecognition process termed heterokaryon or vegetative incompatibility. Incompatibility restricts transmission of mycoviruses between isolates. In P. anserina, genetic analyses have identified nine incompatibility loci, termed het loci. Here we set out to clone the genes controlling het-B incompatibility. het-B displays two incompatible alleles, het-B1 and het-B2. We find that the het-B locus encompasses two adjacent genes, Bh and Bp that exist as highly divergent allelic variants (Bh1/Bh2 and Bp1/Bp2) in the incompatible haplotypes. Bh encodes a protein with an N-terminal HET domain, a cell death inducing domain bearing homology to Toll/interleukin-1 receptor (TIR) domains and a C-terminal domain with a predicted lectin fold. The Bp product is homologous to PII-like proteins, a family of small trimeric proteins acting as sensors of adenine nucleotides in bacteria. We show that although the het-B system appears genetically allelic, incompatibility is in fact determined by the non-allelic Bh1/Bp2 interaction while the reciprocal Bh2/Bp1 interaction plays no role in incompatibility. The highly divergent C-terminal lectin fold domain of BH determines recognition specificity. Population studies and genome analyses indicate that het-B is under balancing selection with trans-species polymorphism, highlighting the evolutionary significance of the two incompatible haplotypes. In addition to emphasizing anew the central role of TIR-like HET domains in fungal RCD, this study identifies novel players in fungal allorecognition and completes the characterization of the entire het gene set in that species. Author summaryMany cellular life forms display genetic systems that protect individuality and discriminate conspecific self from non-self. In filamentous fungi, cell fusion events between strains are under check by specific allorecognition genes that trigger regulated cell death upon detection of non-self. The role of incompatibility is to restrict mycovirus transmission and conspecific parasitism. Podospora anserina, a good model for the study of this form of allorecognition, harbors nine incompatibility het loci. Previous studies have revealed that these genes can be homologous to genes with immune functions in other phyla including bacteria, plants and animals. We have cloned het-B, the last of the nine het genes that remained to be identified and found that it is a complex locus comprising two adjacent genes Bh and Bp. BH displays an N-terminal HET domain (related to TIR domains) and a C-terminal domain with a predicted lectin fold. BP is homologous to PII-like proteins, known bacterial metabolite sensors. Intriguingly, despite apparent genetic allelism, incompatibility is dictated by the non-allelic Bh/Bp interaction. This study stresses the reoccurring involvement of HET domains in fungal RCD and signs completion of the characterization of the entire set of het loci in that species, enabling a comparative analysis of the different genetic architectures underlying allorecognition.

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Clave, C., Dheur, S., Ament-Velasquez, S. L., Granger-Farbos, A., Saupe, S. J.. 2023-12-19. het-B allorecognition in Podospora anserina is determined by pseudo-allelic interaction of genes encoding a HET and lectin fold domain protein and a PII-like protein. https://doi.org/10.1101/2023.12.19.572315

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