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Human evolution offers clues to neurological disorders
A copying error may have been the instigating factor behind features of the human brain that caused human beings to advance beyond their primate ancestors, new research shows.
A copy of the gene SRGAP2 first appeared in our ancestors about 2.5 million years ago. Researchers believe the gene helped our brains work more quickly and make more connections, ultimately allowing the brain to become more complex.
Professor Franck Polleux
When cells divide, they first copy their entire genome, but they can make errors in the process. The cell usually fixes those errors, but when they aren't fixed they become permanent mutations. Those mutations can be helpful, harmful or innocuous.
Duplication, where the cell accidentally copies a part of the genome twice, is one type of copying error. That second copy gives evolution something to work with, since it can be changed in future copies without damaging the organism.
Scripps Research Professor Franck Polleux searched the human genome for these duplications and found that many appear to play a role in the development of the brain.
"There are approximately 30 genes that were selectively duplicated in humans," he said. "These are some of our most recent genomic innovations."
Researchers say SRGAP2 has been duplicated at least twice throughout human evolution, first about 3.5 million years ago, and again around 2.4 million years ago, at about the time that the large-brained species of Homo evolved in Africa from the smaller-skulled Australopithecines. That was also the period when stone tools appeared in the fossil record.
Dr. Polleux said SRGAP2 may have boosted the power of our ancestors' bigger brains by increasing the number of "spines" on the cell surface that connect with other brain cells.
"If you're increasing the total number of connections, you're probably increasing the ability of this network to handle information," he said. "It's like increasing the number of processors in a computer."
The study of human-specific gene duplications could lead to a better understanding of human developmental disorders. Autism and schizophrenia, for example, are known to feature abnormal neuronal connectivity and affect synaptic development, but have been difficult to model accurately in mouse models. Gene duplications such as SRGAP2, which normally don’t occur in mice, could provide important missing pieces of these puzzles.
"We plan to augment existing mouse models by adding some of these human-specific gene duplications," said Dr. Polleux. This approach, called "humanization," has been used successfully in other fields such as immunology for the past two decades to model disease mechanisms, but has so far not been applied to neuroscience.
"This human-specific portion of the genome has not been looked at so far since it is poorly assembled, but we suspect that it might contain the answers to some long-standing mysteries about human diseases," Dr. Polleux said.
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