NACHT and NB-ARC domain proteins containing other types of SSFRs (Dyrka et al.
2014), while other authors insist that the NLR
term should be reserved for proteins with the
NBS-LRR architecture (Yuen et al. 2014). If
NBS-SSFR proteins (with non-LRR-repeats)
indeed act as non-self receptors in a variety of
organisms, notably in fungi, then it appears
advisable to frame the receptors under a common term. This nomenclature would then
account for a possible long-term, parallel evolution of this protein family throughout the tree of
life. This proposed parallel evolution apparently
involved combinatorial recruitment and reassortment of effector, NBS and SSFR domains.
As previously mentioned the resemblance of
animal, fungal, plant, and bacterial NLR-related
genes extends to the N-terminal effector/signaling domains. For instance, kinase domains and
the DUF676 domain are found as N-terminal
domains of NB-SSFR protein s in both fungi
and bryophytes, and PNP_UDP_1 in fungi and
corals, TIR domains are found in plants and
bacteria and the related HET domain in fungi,
and the HeLo-like domain is related to RPW8
domain. In this context, it has been proposed
that STAND proteins (the class to which NLRs
belong) have been acquired in eukaryotes
through horizontal transfer from prokaryotic
origin (Koonin and Aravind 2000, 2002). Therefore, in addition to repeated domain architecture re-invention events (as the ones identified
in fungi), evolution of NLRs might involve horizontal transfer events.
The study by Urbach and Ausubel (2017) reveals the
existence of a limited number of NBS-LRR proteins in
non-plant and non-metazoan eukaryote lineages (6
proteins) and bacteria (12 proteins). Of those, one is
of particular interest and found in the Planctomycetes
Gemmata obscuriglobus. This predicted protein
(GenBank: WP_010049624.1) displays a NACHT NBD
domain and 13 C-terminal LRR-repeats with high internal repeat conservation and an N-terminal domain
showing remote homology to death-fold domains (as
detected by HHPred (Zimmermann et al. 2018)). The
bacterial protein thus displays the same domain architecture as typical metazoan NLRs. Thus, although the
NBS-LRR architecture is exceedingly rare outside of
plant and animal lineages (Urbach and Ausubel 2017),
it does exist, and the possibility that this architecture
has also a long evolutionary history cannot be totally
excluded.
VII. The Exaptation Model: How to
Craft an Allorecognition System
If NLRs have a general function as immune
receptors in fungi, then one needs to explain
why genes of this family have repeatedly been
identified in the context of fungal incompatibility. One plausible explanation for this trend is
that fungal NLRs and other molecular determinants of fungal incompatibility have been evolutionary co-opted to control heterokaryon
formation from other molecular pathways,
notably those controlling organismal defense.
This evolutionary co-optation, also termed
exaptation (Gould and Vrba 1982), would result
in some NLR genes being recruited to play a
role in two distinct biological processes (alloand hetero-recognition, understood as intraand interspecific recognition) and/or to switch
between these processes on the basis of the
evolutionary pressures exercised on the locus.
One tempting speculative model for the emergence of NLR-based incompatibility would be,
in the context of the “guard” model, to coexpress a “guard”—say het-e in P. anserina—
with an independently diverged “guardee”
allele of het-c from a different Podospora strain.
Such “foreign” forms of het-c alleles would
occasionally mimic an active state of the “guardee” for an independently evolved het-e and
lead to the activation of the NLR, resulting in
the emergence of an allorecognition system
(Bastiaans et al. 2014; Paoletti and Saupe
2009). Selective forces driving gene diversification would accelerate the divergence between
an independently evolving “guard” and a
“guardee.” In support of this hypothesis, it has
been reported that molecular marks of positive
selection are found on het-c and the nwd genes
in Podospora, although it is currently not clear
if gene diversification is solely a consequence of
the adaptive value of the allorecognition process itself (Bastiaans et al. 2014). The model of
independently evolving “guard-guardee” pairs
could be applied to the three NLR-encoding
genes—plp-1, het-z, and vic2—triggering heterokaryon incompatibility with different sec-9
homologs in Neurospora, Podospora, and Cryphonectria, respectively (Choi et al. 2012; Heller
et al. 2018).
136
A. Daskalov et al.
2014), while other authors insist that the NLR
term should be reserved for proteins with the
NBS-LRR architecture (Yuen et al. 2014). If
NBS-SSFR proteins (with non-LRR-repeats)
indeed act as non-self receptors in a variety of
organisms, notably in fungi, then it appears
advisable to frame the receptors under a common term. This nomenclature would then
account for a possible long-term, parallel evolution of this protein family throughout the tree of
life. This proposed parallel evolution apparently
involved combinatorial recruitment and reassortment of effector, NBS and SSFR domains.
As previously mentioned the resemblance of
animal, fungal, plant, and bacterial NLR-related
genes extends to the N-terminal effector/signaling domains. For instance, kinase domains and
the DUF676 domain are found as N-terminal
domains of NB-SSFR protein s in both fungi
and bryophytes, and PNP_UDP_1 in fungi and
corals, TIR domains are found in plants and
bacteria and the related HET domain in fungi,
and the HeLo-like domain is related to RPW8
domain. In this context, it has been proposed
that STAND proteins (the class to which NLRs
belong) have been acquired in eukaryotes
through horizontal transfer from prokaryotic
origin (Koonin and Aravind 2000, 2002). Therefore, in addition to repeated domain architecture re-invention events (as the ones identified
in fungi), evolution of NLRs might involve horizontal transfer events.
The study by Urbach and Ausubel (2017) reveals the
existence of a limited number of NBS-LRR proteins in
non-plant and non-metazoan eukaryote lineages (6
proteins) and bacteria (12 proteins). Of those, one is
of particular interest and found in the Planctomycetes
Gemmata obscuriglobus. This predicted protein
(GenBank: WP_010049624.1) displays a NACHT NBD
domain and 13 C-terminal LRR-repeats with high internal repeat conservation and an N-terminal domain
showing remote homology to death-fold domains (as
detected by HHPred (Zimmermann et al. 2018)). The
bacterial protein thus displays the same domain architecture as typical metazoan NLRs. Thus, although the
NBS-LRR architecture is exceedingly rare outside of
plant and animal lineages (Urbach and Ausubel 2017),
it does exist, and the possibility that this architecture
has also a long evolutionary history cannot be totally
excluded.
VII. The Exaptation Model: How to
Craft an Allorecognition System
If NLRs have a general function as immune
receptors in fungi, then one needs to explain
why genes of this family have repeatedly been
identified in the context of fungal incompatibility. One plausible explanation for this trend is
that fungal NLRs and other molecular determinants of fungal incompatibility have been evolutionary co-opted to control heterokaryon
formation from other molecular pathways,
notably those controlling organismal defense.
This evolutionary co-optation, also termed
exaptation (Gould and Vrba 1982), would result
in some NLR genes being recruited to play a
role in two distinct biological processes (alloand hetero-recognition, understood as intraand interspecific recognition) and/or to switch
between these processes on the basis of the
evolutionary pressures exercised on the locus.
One tempting speculative model for the emergence of NLR-based incompatibility would be,
in the context of the “guard” model, to coexpress a “guard”—say het-e in P. anserina—
with an independently diverged “guardee”
allele of het-c from a different Podospora strain.
Such “foreign” forms of het-c alleles would
occasionally mimic an active state of the “guardee” for an independently evolved het-e and
lead to the activation of the NLR, resulting in
the emergence of an allorecognition system
(Bastiaans et al. 2014; Paoletti and Saupe
2009). Selective forces driving gene diversification would accelerate the divergence between
an independently evolving “guard” and a
“guardee.” In support of this hypothesis, it has
been reported that molecular marks of positive
selection are found on het-c and the nwd genes
in Podospora, although it is currently not clear
if gene diversification is solely a consequence of
the adaptive value of the allorecognition process itself (Bastiaans et al. 2014). The model of
independently evolving “guard-guardee” pairs
could be applied to the three NLR-encoding
genes—plp-1, het-z, and vic2—triggering heterokaryon incompatibility with different sec-9
homologs in Neurospora, Podospora, and Cryphonectria, respectively (Choi et al. 2012; Heller
et al. 2018).
136
A. Daskalov et al.