Pre-neuronal origins of monoamine and acetylcholine synthesis and transport
- 1IMBB-FORTH
Abstract
Neuronal architecture is highly modular and individual components can be found in non-neuronal cell types or even neuronless animals, suggesting some functions predate neurons. However, the evolutionary origins of neurotransmitter synthesis, transport and synaptic vesicle biogenesis outside animals remain obscure. To our knowledge, no previous work has systematically addressed the function of neuronal protein homologs outside animals. Our phylogenetic analysis indicates that orthologs of synaptic vesicle (SV) neurotransmitter transporters (SLC18) and synthesis enzymes are widespread in fungi, which, together with animals and sister taxa, form the clade Opisthokonta. Comparing them with their synaptic counterparts can shed light on the emergence of key functions at the animal-fungi split. Here, we combine extensive phylogenetic profiling and statistical analysis with the generation of functional data for these protein families in fungi. We show that monoamine synthesis, orthologous to that of neurons, is present in fungi and places its origin in the opisthokont common ancestor. We also annotate the orthologs of SLC18 transporters showing that they retain an exporter profile and reside predominantly in the endolysosomal system. Building on this observation, we couple deep-learning localization predictions and GO enrichment analysis to show that the phylogenetic context of SVs is lysosomal throughout the Opisthokonta tree, with implications for their phylogenetic origin. In addition, we monitor fungal gene expression in the presence of monoamines showing that they modulate secondary metabolism, hinting at their physiological significance in a neuronless clade. We propose that the machinery associated with neurotransmission originated before animals.
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BibTeX
@misc{pyrris2026preneuronal,
title = {{Pre-neuronal origins of monoamine and acetylcholine synthesis and transport}},
author = {Y. Pyrris and G. Diallinas and A. A. Pittis},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757917},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757917v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Pre-neuronal origins of monoamine and acetylcholine synthesis and transport
AU - Y. Pyrris
AU - G. Diallinas
AU - A. A. Pittis
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757917
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757917v1
AB - Neuronal architecture is highly modular and individual components can be found in non-neuronal cell types or even neuronless animals, suggesting some functions predate neurons. However, the evolutionary origins of neurotransmitter synthesis, transport and synaptic vesicle biogenesis outside animals remain obscure. To our knowledge, no previous work has systematically addressed the function of neuronal protein homologs outside animals. Our phylogenetic analysis indicates that orthologs of synaptic vesicle (SV) neurotransmitter transporters (SLC18) and synthesis enzymes are widespread in fungi, which, together with animals and sister taxa, form the clade Opisthokonta. Comparing them with their synaptic counterparts can shed light on the emergence of key functions at the animal-fungi split. Here, we combine extensive phylogenetic profiling and statistical analysis with the generation of functional data for these protein families in fungi. We show that monoamine synthesis, orthologous to that of neurons, is present in fungi and places its origin in the opisthokont common ancestor. We also annotate the orthologs of SLC18 transporters showing that they retain an exporter profile and reside predominantly in the endolysosomal system. Building on this observation, we couple deep-learning localization predictions and GO enrichment analysis to show that the phylogenetic context of SVs is lysosomal throughout the Opisthokonta tree, with implications for their phylogenetic origin. In addition, we monitor fungal gene expression in the presence of monoamines showing that they modulate secondary metabolism, hinting at their physiological significance in a neuronless clade. We propose that the machinery associated with neurotransmission originated before animals.
ER -