Drawing the line: Clarifying fungal allorecognition from HET domains to het genes to heterokaryon incompatibility
Abstract
The iconic networks of filamentous fungi are connected through hyphal fusions. While fusion is beneficial among hyphae from the same fungal individual, fusion between individuals (i.e., heterokaryon formation) risks infection by parasites or pathogens. Across fungi, multiple sets of genes, termed het genes, have evolved the capacity to prevent the formation of fused hyphae between individuals with incompatible allele combinations. The first het genes to be molecularly characterized function through triggering cell death pathways, forming a paradigm that cell death is the primary mechanism regulating heterokaryon formation. The originally described het genes in the Sordariomycete model fungi Neurospora and Podospora encode a small protein domain, called HET, that is essential in some cases for this cell death function. Since this initial description, the field of fungal self/nonself recognition has progressed in two directions. The experimental side has described het genes in various species, and with increasing mechanistic complexity. More than just cell death, the process of fusion itself has several described checkpoints prior to establishing fusion. These genes, as well as cell death-causing genes in other species, do not encode the characteristic HET domain. However, on the other hand many bioinformatics studies continue to use the HET domain as a primary marker for het genes. This reliance on a limited set of protein domains overlooks general evolutionary features of self/nonself recognition genes, including long-term balancing selection, that may be used to expand searches for undescribed self/nonself loci. We argue here that this singular focus on the HET domain is unproductive and ignores diverse allorecognition mechanisms, including those occurring pre-fusion. A more holistic, process-based view of self/nonself recognition provides a way forward in understanding this fundamental fungal trait, which in turn has cascading consequences for managing fungi in clinical and agricultural settings.
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BibTeX
@article{amentvelasquez2026drawing,
title = {{Drawing the line: Clarifying fungal allorecognition from HET domains to het genes to heterokaryon incompatibility}},
author = {S. Lorena Ament-Velásquez and Conor Bendett and Emile Gluck-Thaler and Asen Daskalov and Ben Auxier},
journal = {Fungal Biology Reviews},
year = {2026},
month = sep,
doi = {10.1016/j.fbr.2026.100499},
url = {https://u-bordeaux.hal.science/hal-05745821v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Drawing the line: Clarifying fungal allorecognition from HET domains to het genes to heterokaryon incompatibility
AU - S. Lorena Ament-Velásquez
AU - Conor Bendett
AU - Emile Gluck-Thaler
AU - Asen Daskalov
AU - Ben Auxier
PY - 2026
DA - 2026/09/10
JO - Fungal Biology Reviews
DO - 10.1016/j.fbr.2026.100499
UR - https://u-bordeaux.hal.science/hal-05745821v1
AB - The iconic networks of filamentous fungi are connected through hyphal fusions. While fusion is beneficial among hyphae from the same fungal individual, fusion between individuals (i.e., heterokaryon formation) risks infection by parasites or pathogens. Across fungi, multiple sets of genes, termed het genes, have evolved the capacity to prevent the formation of fused hyphae between individuals with incompatible allele combinations. The first het genes to be molecularly characterized function through triggering cell death pathways, forming a paradigm that cell death is the primary mechanism regulating heterokaryon formation. The originally described het genes in the Sordariomycete model fungi Neurospora and Podospora encode a small protein domain, called HET, that is essential in some cases for this cell death function. Since this initial description, the field of fungal self/nonself recognition has progressed in two directions. The experimental side has described het genes in various species, and with increasing mechanistic complexity. More than just cell death, the process of fusion itself has several described checkpoints prior to establishing fusion. These genes, as well as cell death-causing genes in other species, do not encode the characteristic HET domain. However, on the other hand many bioinformatics studies continue to use the HET domain as a primary marker for het genes. This reliance on a limited set of protein domains overlooks general evolutionary features of self/nonself recognition genes, including long-term balancing selection, that may be used to expand searches for undescribed self/nonself loci. We argue here that this singular focus on the HET domain is unproductive and ignores diverse allorecognition mechanisms, including those occurring pre-fusion. A more holistic, process-based view of self/nonself recognition provides a way forward in understanding this fundamental fungal trait, which in turn has cascading consequences for managing fungi in clinical and agricultural settings.
SN - 1749-4613
ER -