A study led by Oxford University published in Nature links two ancient whole-genome duplication events to the rise of vertebrate brain complexity. Researchers mapped gene activity in single brain cells from humans, mice, lizards, lampreys and amphioxus, reconstructing cell‑type evolution over 500 million years. The analysis shows that most major vertebrate brain cell families emerged after these duplications.

The team identified retained gene pairs, called ohnologues, as disproportionately active in defining distinct neuronal types. These ancient copies are enriched for regulatory functions, allowing duplicated genes to be repurposed rather than discarded. Such specialization enabled ancestral cell types to split into more refined identities, a process evident across the surveyed species.

Comparisons with amphioxus, a close invertebrate relative, reveal that early regulatory genes were broadly expressed, whereas vertebrate duplicates partitioned these roles among separate cell types. This subfunctionalisation sharpened developmental control and contributed to the layered architecture of modern brains, including cerebellar grey‑matter circuits that continued to draw on the duplicated gene pool.

By tracing gene‑expression signatures from primitive fish to mammals, the researchers demonstrate that the impact of these ancient duplications persisted for hundreds of millions of years. Their work settles a long‑standing debate over whether whole-genome duplications or incremental gene gains drove neuronal diversification, showing that the former supplied the essential raw material for complex brain evolution.