Researchers led by Shi Lei from the Chinese Academy of Sciences discovered that an ancient gene called CCNB1IP1 drives human brain wrinkles and cortical folding, proving that ancient, not newly evolved, genes shaped the human brain.
The human brain features wrinkles and grooves that form the basis for advanced cognition. While traditional theories credited newly evolved genes for this expansion, new research points to ancient origins.
Comparing Embryonic Data Across Species
Shi Lei of the Kunming Institute of Zoology at the Chinese Academy of Sciences tested whether ancient genes altered expression through regulatory elements to shape brain evolution. His team compared transcriptomic data from embryonic cerebral cortex layers across mice, tree shrews, marmosets, macaques, and humans.
Tracing the Rise of CCNB1IP1
The analysis identified the ancient gene CCNB1IP1
. This gene was already present in the tree shrew brain—a primate relative—at low levels before primates emerged.
Expression increased stepwise across tree shrews, marmosets, macaques, and humans, where it peaked. Marmosets have smooth brains and match tree shrew expression levels, while macaques show elevated expression and folded brains. The human brain shows the highest expression, driven by a regulatory sequence the team identified as CRE1.
Engineering Cortical Folding in Mice
The researchers created a gene knock-in mouse model to verify the function of CCNB1IP1. While normal mice have smooth cerebral cortices, the modified mice developed cortical folding structures. These modified mice subsequently displayed enhanced learning and memory abilities.
Investigating Neural Development Disorders
These findings provide a new perspective on human brain evolution and offer potential targets for investigating neural development disorders. Earlier reporting noted that lower bone mineral density is linked to accelerated brain aging.
