- Happy to see this out! "Reconstructing NOD-like receptor alleles with high internal conservation in #Podospora anserina using long-read sequencing", now in @microbiologysociety.org! 🧬 Keep reading for a simple explanation 🧵 1/n #Fungi #Allorecognition www.microbiologyresearch.org/content/jour...
- NOD-like receptors (NLRs) are intracellular proteins that play key roles in the innate immune system of plants and animals. But in fungi we know the function of only a few cases: they all work in heterokaryon incompatibility (rejection between different strains during vegetative fusion). 2/n
- In the model fungus #Podospora anserina, the het-d and het-e NLRs are highly polymorphic genes, whose products recognize different alleles of another gene, het-c. If two confronting strains have incompatible het-e/d and het-c alleles, a rejection reaction occurs. 3/n
- het-d/e have "high internal conservation" (HIC): their C-term domain is made out of nearly identical WD40 repeats. Only a few sites are different and evolve under diversifying selection. Concerted evolution (or something) homogenizes the repeats and leads to loss, gain, and shuffling of repeats. 4/n
- Of course, these HIC repeats are hard to sequence. We showed that assemblies of Illumina reads often recover broken or incorrect (!) allele reconstructions. But #PacBio and #Nanopore data get them just fine. 5/n #genomics
- We sequenced a panel of strains with known alleles, which can now be used to assign a phenotype to wild-type strains. With this information in hand, we determined that reactive alleles fold into two beta-propellers that likely embrace their cognate ligand HET-C like a clam. 6/n #AlphaFoldJul 2, 2025 18:10
- Are het-d and het-e capable of recognizing het-c because of shared ancestry? No! It turns out they are not that closely related, judging by phylogenies along the gene for a bunch of NLRs in Podospora. 7/n
- For the repeat domain, we extracted >1100 individual repeats and performed a PCA of their nucleotide sequences. Indeed, het-d and het-e are not that similar, but we discovered that het-e seems to be exchanging repeats with another gene! 8/n
- So in conclusion, het-d and het-e independently evolved the capacity of recognizing het-c, even in the presence of interparalog repeat exchange! This little story is relevant for NLRs in general, as ~13% of all fungal NLRs and a lot of bacterial NLRs have HIC repeats! end/n #Bacteria #immunity
- This work was done in both Stockholm and Bordeaux Universities as part of my Vetenskapsrådet postdoc mobility grant. I am grateful to my co-authors and to everybody who supported me along the way! Yay!!
