The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these ‘human accelerated regions’, HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal–Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal–Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.
Scientists say they have discovered a gene sequence which appears to play a central role in giving humans their unique brain capacity.
The area, called HAR1, has undergone accelerated evolutionary change in humans and is active during a critical stage in brain development.
The researchers compared genes from humans, chimpanzees and other animals to try to see which set man apart.
The Nature study was led by the University of California, Santa Cruz.
Something caused our brains to evolve to be much larger and have more functions than the brains of other mammals
Dr David Haussler
The researchers say they have yet to determine the precise function of the gene.
But they say the evidence suggests it may play a role in the development of the cerebral cortex – and may help explain the dramatic expansion of this part of the brain during human evolution.
They used a sophisticated computer analysis technique to compare genes from various species and pinpoint those which have undergone accelerated evolutionary changes in humans.
This highlighted the HAR1 region of the human genome.
Specialised nerve cells
The researchers examined this area more closely in the lab to pin down its structure, the tissues in which it is active, and to try to better understand its function.
They found HAR1 was part of two overlapping genes, of which one – HAR1F – was active in special nerve cells called Cajal-Retzius neurons.
These cells appear early in embryonic development and play a critical role in the formation of the layered structure of the human cerebral cortex.
Cajal-Retzius neurons release a protein called reelin that guides the growth of neurons and the formation of connections among them.
HAR1F was found to be active at the same time as the reelin gene.
Lead researcher Dr David Haussler said: “We don’t know what it does and we don’t know if it interacts with reelin.
“But the evidence is very suggestive that this gene is important in the development of the cerebral cortex and that’s exciting because the human cortex is three times as large as it was in our predecessors.
“Something caused our brains to evolve to be much larger and have more functions than the brains of other mammals.”
The analysis showed that HAR1 is essentially the same in all mammals except humans. There were just two differences between the versions found in chickens and chimps.
However, there were 18 differences between the chimp version and the one found in humans – which scientists say is an incredible amount of change to take place in a few million years.
The researchers believe the key gene does not control the production of specific proteins as most genes do, but instead plays a role in modifying the function of other genes.
Professor Chris Ponting, of the University of Oxford, said this suggested that the rapid evolution of the human brain might be due to subtle fine-tuning of genetic function.
His colleague, Dr Gerton Lunter, said: “What is really interesting is that this is a special type of gene.
“It seems likely that it changes the way the brain is wired in some way.”
From 5 minutes 21 seconds in the History Channel movie above, they also talk about the HAR1