NeuroSystematics and Periodic System of Neurons: Model vs Reference Species at Single-Cell Resolution.

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes (=convergent evolution). Neurons are different not only because they have different functions, but also because neurons and circuits have different genealogies, and perhaps independent origins at the broadest scale from ctenophores and cnidarians to cephalopods and primates. By combining modern phylogenomics, single-neuron sequencing (scRNA-seq), machine learning, single-cell proteomics, and metabolomic across Metazoa, it is possible to reconstruct the evolutionary histories of neurons tracing them to ancestral secretory cells. Comparative data suggest that neurons, and perhaps synapses, evolved at least 2-3 times (in ctenophore, cnidarian and bilateral lineages) during ∼600 million years of animal evolution. There were also several independent events of the nervous system centralization either from a common bilateral/cnidarian ancestor without the bona fide neurons or from the urbilaterian with diffuse, nerve-net type nervous system. From the evolutionary standpoint, (i) a neuron should be viewed as a functional rather than a genetic character, and (ii) any given neural system might be chimeric and composed of different cell lineages with distinct origins and evolutionary histories. The identification of distant neural homologies or examples of convergent evolution among 34 phyla will not only allow the reconstruction of neural systems' evolution but together with single-cell "omic" approaches the proposed synthesis would lead to the "Periodic System of Neurons" with predictive power for neuronal phenotypes and plasticity. Such a phylogenetic classification framework of Neuronal Systematics (NeuroSystematics) might be a conceptual analog of the Periodic System of Chemical Elements. scRNA-seq profiling of all neurons in an entire brain or Brain-seq is now fully achievable in many nontraditional reference species across the entire animal kingdom. Arguably, marine animals are the most suitable for the proposed tasks because the world oceans represent the greatest taxonomic and body-plan diversity.