Tracing the Evolutionary Histories of Human Cholinergic Proteins Across Eukaryotes: A Comparative Phylogenomic Study

Human cholinergic proteins show heterogeneous evolutionary histories across 89 eukaryotic proteomes, with distinct bilaterian, vertebrate, and echinoderm-associated groupings emerging for different protein groups.

• Why it matters: Cholinergic signaling relies on multiple enzymes, transporters, and receptors whose evolutionary trajectories may not match, limiting how well comparative studies can interpret lineage-specific evolution.
• What they did: Using a human-reference-anchored phylogenomic framework, the study analyzed 26 curated human cholinergic reference proteins via similarity searches, domain/orthology checks, family phylogenies, and gene-tree/species-tree reconciliation for selected datasets.
• The result: CHAT- and SLC18A3-associated candidates appear across multiple bilaterian lineages, SLC5-family sequences span ctenophores, cnidarians, and bilaterians with a vertebrate-associated subgroup linked to human SLC5A7, and cholinesterases form echinoderm and distinct vertebrate ACHE/BCHE groups with lower deeper support.

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