New research published in Nature sheds light on how vertebrates developed the wide variety of brain cells that set them apart from other animals. The findings indicate that a major increase in genetic material more than 450 million years ago supported the rise of specialized brain cells. These changes are common to vertebrates from early fish to mammals and underpin the advanced brains observed today.
Researchers compared gene activity in single brain cells from five species: humans, mice, lizards, lampreys, and amphioxus. This approach allowed them to trace the evolution of brain cell types over long periods.
The study identified that many key cell type groups in vertebrate brains emerged after a genome duplication in the vertebrate ancestor about 520 million years ago, followed by another around 500 million years ago.
Professor Sebastian Shimeld of the University of Oxford noted that these two genetic doubling events provided the foundation for complex brains. Duplicating the entire genome supplied material that could be adapted to create new brain cell types.
Whole-genome duplication involves copying all genetic material in an organism. Scientists have discussed whether brain cell expansion resulted from these events or from smaller, gradual gene duplications.
Many duplicated genes are lost, but some persist and acquire new or specialized functions over time.
The team observed that gene pairs retained from whole-genome duplications, called ohnologues, play a major role in defining distinct brain cell types. Across the species studied, these genes were far more likely to be active in specific brain cells than genes duplicated by other means. They were particularly linked to regulatory functions that control cell development and activity.
Evidence also showed that early vertebrate brains evolved by splitting ancestral cell types into more specialized forms. In simpler relatives like amphioxus, key regulatory genes operate across many cells. In vertebrates, duplicated versions of these genes function in separate cell types, establishing unique identities.
Most duplicated genes did not gain entirely new roles. Instead, they divided the original gene’s functions, refining the range of brain cell types.
The effects of these ancient events continued long after early vertebrate evolution. Analysis of later-evolving brain cells, such as those in the cerebellum, showed that genes from these duplications helped define new cell types over hundreds of millions of years.
The results demonstrate how uncommon genomic changes can produce lasting effects on animal complexity.
Co-author Professor Peter Holland stated that the analyses were highly complex, but the outcome is straightforward: new brain cells required new genes from early DNA doublings before fish appeared.
