Whole genome duplication drove cell type evolution in the vertebrate brain

The brains of vertebrates are more complex and have a wider diversity of cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution ¹ , but it remains unclear whether the resultant duplicate genes (ohnologues) facilitated cell type evolution. Using brain single-cell transcriptomes from four vertebrates – human, mouse, lizard, and lamprey – we find major cell type families are conserved with shared core transcription factors. If WGD was more important for cell type evolution than other types of gene duplication then we predict that cell type markers will be likely to be ohnologues, and that ohnologue pairs will be used in cell type-specific patterns. We show both predictions hold, demonstrating ohnologues play more prominent roles in cell type evolution than genes duplicated by other routes. By examining expression of paralogues across cell types and species, we show that expression changes have been mainly driven by dosage selection and subfunctionalization. We then show these processes boosted cellular diversity at different anatomical and cell type scales. Our findings demonstrate systematic and long-lasting effects that potentiated vertebrate brain cell type evolution for hundreds of millions of years following WGD.