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

Area of Science:

• Evolutionary biology
• Neuroscience
• Genomics

Background:

• Vertebrate brains exhibit greater cell-type diversity than their closest relatives.
• Whole-genome duplications (WGDs) occurred during early vertebrate evolution, but their role in cell-type evolution remains debated.
• The function of duplicated genes (ohnologues) in facilitating vertebrate brain complexity is not fully understood.

Purpose of the Study:

• To investigate the role of whole-genome duplications (WGDs) and their resultant duplicated genes (ohnologues) in the evolution of vertebrate brain cell types.
• To determine if ohnologues were mechanistically important for early vertebrate cell-type diversification.
• To explore the evolutionary dynamics of ohnologues and their contribution to cellular diversity.

Main Methods:

• Comparative analysis of single-cell transcriptomes from five chordates: human, mouse, lizard, lamprey, and amphioxus.
• Prediction of ancestral cell-type states and comparison with extant species, including experimental investigation of macroglia.
• Examination of paralogue expression across cell types and species to identify drivers of expression changes.

Main Results:

• Many vertebrate cell-type families with conserved transcription factors lack one-to-one homology with amphioxus.
• Ohnologues, especially from the first WGD, played a more significant role in cell-type evolution than small-scale duplication paralogues.
• Expression changes in ohnologues were primarily driven by dosage selection and subfunctionalization, linking them to cellular diversity.

Conclusions:

• Whole-genome duplications were critical for the evolution of early vertebrate brain complexity.
• Ohnologues facilitated early vertebrate cell-type diversification and continued to drive cell-type evolution.
• The study highlights the long-term impact of WGDs on the evolution of complex nervous systems.