Evolutionary principles underlying neuron subtype encoding and diversification in animals

and performing cell type comparisons across protostome and deuterostome species, we show that neuronal subtypes in one species bear little resemblance to those found in different phyla. Previously identified cross-phyletic transcriptional similarities represent exceptions to a global pattern of divergence. Specifically, we observe that all neurons share the expression of genes associated with general features such as the presynapse and axon cytoskeleton, but distantly related species have evolved distinct usage of subtype-defining genes: they co-express unique combinations of neurotransmitter pathways, ion channels, postsynaptic receptors, and transcription factors. Additionally, we recover signal for an ancient neuronal regulatory code characterized by a strong enrichment for homeodomain transcription factors. Overall, these results suggest that while neurons largely share a core set of transcriptional features, a great deal of reshuffling of gene expression has occurred, supporting large-scale turnover in neuron subtype identities amongst major animal lineages.