VIII. Conclusions
In this chapter, we recapitulate the state of
knowledge on the large family of fungal NODlike receptors, identified and investigated as
allorecognition determinants in several filamentous ascomycete species. Subsequent in
silico analyses revealed that NLR proteins are
widespread in the fungal kingdom, display
remarkable architectural variability, and carry
accessory signaling/executioner domains,
which appear in some cases homologous to
counterparts in metazoan and plant NLRs.
The accumulation of observational and experimental data has led to the hypothesis that the
fungal NLRs are an integral part of a complex
and yet to be fully described fungal immune
system that may play roles both in host defense
and symbiotic interactions. Future approaches
will need to demonstrate the involvement of a
fungal NLR protein in direct mediation of heterospecific non-self recognition to establish a
broader functional equivalence between the
fungal NLR type and the NLR receptors that
have been shown to control innate immunity
in other major eukaryotic lineages. This
achievement would impact not only NLR biology but also our general understanding of the
molecular evolution of non-self discrimination
in eukaryotes and possibly beyond, in some
prokaryotic species. The ascertainment that
these proteins belong to the same family, have
a shared evolutionary origin, and mediate heterospecific non-self discrimination in three of
the main branches in Eukaryota, would validate
these use of a common conceptual framework
for the investigation of commonalities and particularities in the molecular mechanics and
evolutionary strategies of diversification of the
NOD-like receptors in plants, metazoans, and
fungi (and perhaps also in multicellular prokaryotes). The likely prokaryotic origin of programmed cell death and innate immunity
machinery has been repeatedly stressed (Aravind and Koonin 2002; Dunin-Horkawicz et al.
2014; Koonin and Aravind 2002). Some commonality appears in the genome content of
NLR-type gene architectures in fungi and bacteria. In both cases, the architecture is prevalent
in filamentous/multicellular species and rare or
absent in unicellular species. NB-ARC TPR and
NACHT WD architectures are abundant, and
SSFRs with high internal repeat conservation
occur frequently in both branches. It will be of
great interest in the future to gain some insight
into the evolutionary and functional basis of
this resemblance in the NLR-type gene content
in prokaryotic and eukaryotic multicellular
microbes.
Many aspects of fungal biology are currently contemplated in the context of interorganismal interactions (endophytic and
mycorrhizal lifestyles, lichen formation, pathogenicity, mycoparasitism, fungal-bacterial
interactions, control of secondary metabolism).
If indeed the large and diversified repertoires of
NLRs in fungi have a general role in sensing
and responding to a variety of biotic cues, then
it can safely be predicted that this family of
proteins will turn out to be of some importance
for the future of our understanding of the myriad of fungal lifestyle modalities.
Acknowledgments The authors thank Corinne Clave ´
for critical reading of the manuscript. This work was
supported in part by the National Science Centre of
Poland (grant no. 2015/17/D/ST6/04054) and an ANR
grant (SFAS, ANR-17-CE11-0035-01). AD was supported by a Laboratory Directed Research and Development Program of Lawrence Berkeley National
Laboratory under the US Department of Energy Contract No. DE-AC02-05CH11231.
References
Aanen DK, Debets AJM, Glass NL, Saupe SJ (2010)
Biology and genetics of vegetative incompatibility
in fungi. In: Borkovich KA, Ebbole DJ (eds) Cellular and molecular biology of filamentous fungi.
Washington, DC, ASM Press, pp 274–288
Aravind L, Koonin EV (2002) Classification of the
caspase-hemoglobinase fold: detection of new
families and implications for the origin of the
eukaryotic separins. Proteins 46:355–367
Bastiaans E, Debets AJ, Aanen DK, van Diepeningen
AD, Saupe SJ, Paoletti M (2014) Natural variation
of heterokaryon incompatibility gene het-c in
Podospora anserina reveals diversifying selection.
Mol Biol Evol 31:962–974
138
A. Daskalov et al.
In this chapter, we recapitulate the state of
knowledge on the large family of fungal NODlike receptors, identified and investigated as
allorecognition determinants in several filamentous ascomycete species. Subsequent in
silico analyses revealed that NLR proteins are
widespread in the fungal kingdom, display
remarkable architectural variability, and carry
accessory signaling/executioner domains,
which appear in some cases homologous to
counterparts in metazoan and plant NLRs.
The accumulation of observational and experimental data has led to the hypothesis that the
fungal NLRs are an integral part of a complex
and yet to be fully described fungal immune
system that may play roles both in host defense
and symbiotic interactions. Future approaches
will need to demonstrate the involvement of a
fungal NLR protein in direct mediation of heterospecific non-self recognition to establish a
broader functional equivalence between the
fungal NLR type and the NLR receptors that
have been shown to control innate immunity
in other major eukaryotic lineages. This
achievement would impact not only NLR biology but also our general understanding of the
molecular evolution of non-self discrimination
in eukaryotes and possibly beyond, in some
prokaryotic species. The ascertainment that
these proteins belong to the same family, have
a shared evolutionary origin, and mediate heterospecific non-self discrimination in three of
the main branches in Eukaryota, would validate
these use of a common conceptual framework
for the investigation of commonalities and particularities in the molecular mechanics and
evolutionary strategies of diversification of the
NOD-like receptors in plants, metazoans, and
fungi (and perhaps also in multicellular prokaryotes). The likely prokaryotic origin of programmed cell death and innate immunity
machinery has been repeatedly stressed (Aravind and Koonin 2002; Dunin-Horkawicz et al.
2014; Koonin and Aravind 2002). Some commonality appears in the genome content of
NLR-type gene architectures in fungi and bacteria. In both cases, the architecture is prevalent
in filamentous/multicellular species and rare or
absent in unicellular species. NB-ARC TPR and
NACHT WD architectures are abundant, and
SSFRs with high internal repeat conservation
occur frequently in both branches. It will be of
great interest in the future to gain some insight
into the evolutionary and functional basis of
this resemblance in the NLR-type gene content
in prokaryotic and eukaryotic multicellular
microbes.
Many aspects of fungal biology are currently contemplated in the context of interorganismal interactions (endophytic and
mycorrhizal lifestyles, lichen formation, pathogenicity, mycoparasitism, fungal-bacterial
interactions, control of secondary metabolism).
If indeed the large and diversified repertoires of
NLRs in fungi have a general role in sensing
and responding to a variety of biotic cues, then
it can safely be predicted that this family of
proteins will turn out to be of some importance
for the future of our understanding of the myriad of fungal lifestyle modalities.
Acknowledgments The authors thank Corinne Clave ´
for critical reading of the manuscript. This work was
supported in part by the National Science Centre of
Poland (grant no. 2015/17/D/ST6/04054) and an ANR
grant (SFAS, ANR-17-CE11-0035-01). AD was supported by a Laboratory Directed Research and Development Program of Lawrence Berkeley National
Laboratory under the US Department of Energy Contract No. DE-AC02-05CH11231.
References
Aanen DK, Debets AJM, Glass NL, Saupe SJ (2010)
Biology and genetics of vegetative incompatibility
in fungi. In: Borkovich KA, Ebbole DJ (eds) Cellular and molecular biology of filamentous fungi.
Washington, DC, ASM Press, pp 274–288
Aravind L, Koonin EV (2002) Classification of the
caspase-hemoglobinase fold: detection of new
families and implications for the origin of the
eukaryotic separins. Proteins 46:355–367
Bastiaans E, Debets AJ, Aanen DK, van Diepeningen
AD, Saupe SJ, Paoletti M (2014) Natural variation
of heterokaryon incompatibility gene het-c in
Podospora anserina reveals diversifying selection.
Mol Biol Evol 31:962–974
138
A. Daskalov et al.