Whole genome duplication shaped cell-type evolution in the vertebrate brain

Journal article

The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution, but it is unclear if the duplicated genes (ohnologues) facilitated cell-type evolution. Using brain singlecell transcriptomes from five chordates – human, mouse, lizard, lamprey, and amphioxus – we find many novel cell-type families with conserved core transcription factors in vertebrates which do not show 1-to-1 homology with amphioxus. We show that ohnologues, particularly those from the first WGD, were more important than small-scale duplication (SSD) paralogues for novel vertebrate cell types. To explore whether ohnologues were mechanistically important for new cell types, we predict ancestral cell-type states to compare to amphioxus and experimentally investigate macroglia development. Our results support a role for ohnologues in early vertebrate cell-type diversification. 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 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 indicate the resultant ohnologues continued to capacitate cell-type evolution long after they were formed.

Authors: Zhu, Y; Zhang, S; Wei, J; Dolgetta-Garcia, D; Jindrich, K

• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature
• Acceptance date: 2026-04-13
• DOI: 10.21203/rs.3.rs-6965966/v1
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English