About 2.4 million years ago a gene that controls brain development was duplicated in the human genome. And then another copy appeared a million years later. This apparently is why our brains got smarter than the other apes. But the duplicate genes don't do what you'd think that they're doing. Quite the opposite:
A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors' genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.
What genetic changes account for the vast behavioral differences between humans and other primates? Researchers so far have catalogued only a few, but now it seems that they can add a big one to the list. A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors' genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.
Surprisingly, the added copy doesn't augment the function of the original gene, SRGAP2, which makes neurons sprout connections to neighboring cells. Instead it interferes with that original function, effectively giving neurons more time to wire themselves into a bigger brain.
"This appears to be a major example of a genomic innovation that contributed to human evolution," said Franck Polleux, a professor at The Scripps Research Institute. "The finding that a duplicated gene can interact with the original copy also suggests a new way to think about how evolution occurs and might give us clues to human-specific developmental disorders such as autism and schizophrenia."
Polleux is the senior author of the new report, which was published online ahead of print on May 3, 2012 by the journal Cell. The same issue features a related paper on SRGAP2's recent evolution by the laboratory of Evan E. Eichler at the University of Washington, Seattle.
Polleux specializes in the study of human brain development, and, several years ago, his lab began researching the function of the newly-discovered SRGAP2. He and his colleagues found that in mice, the gene's protein product plays a key role during brain development: It deforms the membranes of young neurons outward, forcing the growth of root-like appendages called filopodia. As young neurons sprout these filopodia, they migrate more slowly through the expanding brain; eventually they reach their final position where they form connections. Most excitatory connections made on pyramidal neurons in the cortex are formed on spines, which are microscopic protrusions from the dendrite playing a critical role in integrating synaptic signals from other neurons.
Shortly after beginning the project, Polleux learned from other labs' work that SRGAP2 was among the few genes (approximately 30) that had been duplicated in the human genome less than six million years ago after separation from other apes. "These evolutionarily recent gene duplications are so nearly identical to the original genes that they aren't detectable by traditional genome sequencing methods," said Polleux. "Only in the last five years have scientists developed methods to reliably map these hominid-specific duplications."
The whole story here.
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