The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution ¹ , but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human ² , mouse ³ , lizard ⁴ , lamprey ⁵ and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show one-to-one homology with amphioxus. Moreover, ohnologues, particularly those from the first WGD, were more important than small-scale duplication paralogues for vertebrate cell-type evolution. To explore whether ohnologues are mechanistically important for this process, we predicted ancestral cell-type states and compared them to amphioxus and experimentally investigated macroglia. The findings indicate that ohnologues had a role in early vertebrate cell-type diversification. Moreover, by examining paralogue expression across cell types and species, we show that expression changes were mainly driven by dosage selection and subfunctionalization. We also link ohnologues to cellular diversity at different anatomical and cell-type scales. Our findings demonstrate the importance of WGDs for the evolution of early vertebrate brain complexity and highlight that the resultant ohnologues continued to capacitate cell-type evolution long after they were formed.

Cell types are fundamental biological units and partially independent evolutionary units, shaped by individualised gene regulatory networks and developmental lineages. Despite the recent explosion in single-cell sequencing and increased attention on cell characterization, we still lack a unified and consistent naming system for cell types that works across species. Since cell types are the products of evolutionary diversification, we propose that cell-type names should explicitly reflect evolutionary history, and suggest a naming system with a phylogenetic representation prefix as a simple, informative and intuitive way to do this. The key to this is establishing the evolutionary/taxonomic level of comparison, coupled with understanding homology and innovation in cell-type evolution. Put simply, it can apply to both individual cell types and their clades. We illustrate this approach using two case studies: chordate macroglia and more explicitly on vertebrate photoreceptors. The long-term goal is to stimulate progress towards a more coherent and informative language for cell-type identity and comparative analyses that is evolutionarily extendable as single-cell research proliferates across the tree of life.