A recent study has revealed that a specific segment of human DNA can significantly enhance brain size and complexity in mice, providing crucial insights into the evolutionary development of the human brain. Conducted at Duke University and published in May 2025, this research highlights how particular genetic alterations can stimulate the growth of larger, more intricate brains.
The researchers introduced a human DNA segment, called HARE5, into mice. The introduction of HARE5 resulted in a notable 6.5% increase in brain size. HARE5 is categorized as a Human Accelerated Region (HAR), which denotes a DNA sequence that has undergone rapid evolution in humans compared to other mammals. These HARs typically function as enhancers, modulating the activity of genes vital for developmental processes.
The study demonstrated that the human variant of HARE5 amplifies the activity of the Frizzled8 (Fzd8) gene, which is critical for early brain development. Mice carrying the humanized HARE5 showed an increase in radial glia, which are neural stem cells responsible for producing neurons. This increase led to a greater number of excitatory neurons and a more refined brain circuitry. Additional experiments using brain organoids derived from human and chimpanzee stem cells verified that human HARE5 boosted radial glial proliferation and accelerated maturation by enhancing the WNT signaling pathway. These findings underscore the profound impact that minor genetic changes can have on brain development and evolution, potentially paving the way for future treatments for neurological disorders.