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Thanks to our amazing team and collaborators @maribelnm.bsky.social. Excited to hear your thoughts!
#Epigenetics #RNAi #RNA #RNAbiology #Inheritance #Meiosis #Genomics #AMR #DrugResistance #FungalPathogens #IDSky #Fungi

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Beyond infectious diseases, epimutations also push the boundaries of what we know about inheritance, showing RNA can serve as an information molecule across generations.
RNA-based epigenetic inheritance might echo the ancient “RNA world”, where RNA was considered the original molecule of life.

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Why this matters:
Epimutations may explain pervasive and reversible antifungal drug resistance in Mucoralean pathogens, a serious concern for immunocompromised patients.

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Epimutations were inherited in non-Mendelian ratios, even when the offspring’s DNA came from a drug-susceptible parent.
The resistance was carried only by small RNAs, uncoupled from histone modifications or DNA methylation typically associated with epigenetic inheritance in other organisms.

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We mated our epimutants and tracked the fate of these epimutations in their progeny, confirming meiosis through whole-genome sequencing.
Check out our new nearly telomere-to-telomere reference genomes here:
🔗 www.ncbi.nlm.nih.gov/datasets/gen...
🔗 www.ncbi.nlm.nih.gov/datasets/gen...

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Here is the big question:
Can RNAi-based changes be passed on through sexual reproduction?

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In Mucor circinelloides, these epimutations are entirely RNA-based.
They silence the drug target gene FKBP12 through small RNAs, granting resistance to FK506. Resistance appears when the pathogen faces the drug and disappears when the pressure is gone.
Like switching drug resistance on and off ⏯️

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Fungi can resist antifungal drugs without mutating their DNA. Instead, they use epimutations, heritable changes in gene expression driven by RNA interference or chromatin modifications.