The emergence of vertebrates represents a major transition in the history of life, marked by the origin of innovative features such as the vertebral column, neural crest and endoskeleton. The vertebrate brain also became enormously complex, giving rise to structures with distinct morphological and functional specializations, including the telencephalon, diencephalon and cerebellum, which greatly enhanced the ability of vertebrates to adapt to diverse ecological niches.The whole-genome duplication (WGD) events that occurred early in vertebrate evolution have long been considered key drivers of structural innovation and complexity in vertebrate organs. However, direct evidence for the contribution of WGD to the evolution of vertebrate brain cell types and to the overall increase in brain complexity has remained scarce.
On 10 June 2026, a study led by Professor Sebastian Shimeld (Department of Biology, University of Oxford) and Professor Guang Li (School of Life Sciences, Xiamen University) was published in Nature titled “Whole genome duplication shaped cell-type evolution in the vertebrate brain”. Through systematic comparative analyses of brain cell-type evolution across five chordate species — human, mouse, lizard, lamprey and amphioxus — the researchers found that genes retained from whole-genome duplication (ohnologues) played a critical role in the diversification of early vertebrate brain cell types.
The study reconstructed cell-type families of the ancestral vertebrate state and a set of core transcription factors conserved across species from an evolutionary perspective. By comparing the cell types of amphioxus with the inferred ancestral vertebrate state, the authors found no one-to-one homologous cell types between them. Consequently, both in this paper and in a companion preprint perspective, the authors propose the possibility of “cell-type radiation” during early vertebrate evolution.
By analyzing the relationship between WGD-retained genes (ohnologues) and the evolution and diversity of cell types at different hierarchical levels, the researchers discovered a strong causal link between ohnologues and the emergence and subsequent evolution of vertebrate cell types. In particular, in the evolution of the macroglia cell-type family — including astrocytes, ependymal cells and oligodendrocytes — functional validation and a new theoretical framework revealed that the functional specialization of key transcription factors following WGD-driven duplication was essential for the early evolution and diversification of macroglia in the vertebrate brain.
The authors also systematically investigated the evolutionary patterns of duplicated genes at the cell-type level, revealing that subfunctionalization and dosage balance are key mechanisms underlying the retention and divergence of ohnologues. The study further demonstrates that, from large cell-type families at the brain-region scale and brain regionalization regulatory programs, to the specialization of cell subtypes and cerebellar nuclear excitatory neurons, and even to the evolution of other organs and tissues, all are closely associated with the long-term retention and functional divergence of ohnologues. The authors point out that WGD not only profoundly shaped the evolutionary trajectory of brain cell types in early vertebrates, but also continuously drove the formation and functional innovation of cerebellar nuclei subclasses during the origins of amniotes and mammals. The research reveals both the short- and long-term impacts of WGD on vertebrate brain cell-type evolution and provides a robust perspective on the fundamental evolutionary question of how new cell types arise.
A preprint perspective published simultaneously alongside the research article, “Towards a Rational Terminology for Cell Types”, further discusses, at the theoretical level, the concept of the cell type itself as a unit of evolution. This perspective attempts to address a core question emerging in the single-cell era: as cross-species cell atlases are being generated for a growing number of organisms, how should we define, compare and name cell types across different species? The authors argue that cell types should not be named solely on the basis of function, morphology or marker genes, but should be understood within a phylogenetic and evolutionary framework. To this end, they propose a “phylogenetic representation prefix” nomenclature system that encodes the evolutionary origin directly into the cell name — for example, “Vertebrata astrocytes” and “Gnathostomata oligodendrocytes” — to reflect cell-type homology and levels of innovation. This system can be applied across different hierarchical scales, from cell subtypes to large cell families.
At the same time, the authors update several core concepts in cell evolution theory, such as the definition of a new cell type and the sister cell-type hierarchy. Using vertebrate photoreceptors as a case study, they construct a photoreceptor evolutionary tree and highlight the advantages of the new nomenclature. The article notes that, as cross-species single-cell initiatives like the Biodiversity Cell Atlas advance, a unified naming framework that accommodates homology, novelty and hierarchy will become an essential foundation for understanding cellular diversity in both plants and animals.
Yuanzhen Zhu, a doctoral student at the University of Oxford, Professor Guang Li from the School of Life Sciences, Xiamen University, and Professor Sebastian Shimeld from the Department of Biology, University of Oxford, are the co-corresponding authors of the paper. Yuanzhen Zhu is the first author. Graduate student Shuai Zhang, master’s graduate Huimin Liu, and PhD graduates Chenggang Shi and Rongrong Pan from Professor Guang Li’s group at Xiamen University also made significant contributions to this research. This work was funded by the National Natural Science Foundation of China (grant numbers 32270439, 32570616, 32522017 and 32370461), the Science & Technology Innovation Project of Laoshan Laboratory (LSKJ202203001), the Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/Z51746X/1 and BB/X015203/1, among others.
Original article link: https://www.nature.com/articles/s41586-026-10629-x
