Evolutionary principles underlying neuron subtype encoding and diversification in animals.

Area of Science:

• Evolutionary biology
• Neuroscience
• Genomics

Background:

• Animals possess diverse, terminally differentiated cell types, especially in the nervous system.
• The evolutionary origin of neurons is supported, but the timing and mechanisms of neuron diversification remain unclear.
• Current models of neuronal evolution rely on limited species comparisons, lacking a systems-level perspective.

Purpose of the Study:

• To investigate the diversification of neuron subtypes across major animal lineages.
• To identify molecular mechanisms underlying neuron subtype evolution.
• To compare neuronal transcriptomes across protostome and deuterostome species.

Main Methods:

• Single-cell RNA-sequencing was applied to the acorn worm *Saccoglossus kowalevskii*.
• Comparative transcriptomic analysis was performed across diverse protostome and deuterostome species.
• Neuronal gene expression patterns, including neurotransmitter pathways and transcription factors, were analyzed.

Main Results:

• Neuronal subtypes show limited resemblance across distantly related phyla, indicating divergence.
• All neurons share core genes for presynaptic and axonal functions.
• Species-specific combinations of subtype-defining genes (neurotransmitters, receptors, transcription factors) were identified.
• An ancient neuronal regulatory code enriched for homeodomain transcription factors was recovered.

Conclusions:

• Neuron subtype identities have undergone significant turnover and divergence across major animal lineages.
• While sharing fundamental transcriptional features, species evolve distinct neuron subtypes through unique gene co-expression.
• A conserved regulatory code involving homeodomain transcription factors may have guided early neuron diversification.