Researchers discover genes that distinguish human, nonhuman primate brains

Findings shed light on the evolution of human cognition, the capacity for long lifespan and the potential for neurodegenerative disease

A research team from the Salk Institute, the Yerkes National Primate Research Center of Emory University and the University of California – Los Angeles (UCLA), has identified genes in the cerebral cortex that differ in levels of activity between humans and nonhuman primates, including chimpanzees and rhesus monkeys. These findings, which appear in the online journal of the Proceedings of the National Academy of Sciences, may provide essential clues to the unusual cognitive abilities of humans. They also may help researchers understand why humans have a longer lifespan than other primate species and yet are so vulnerable to age-related, neurodegenerative diseases.

Because the DNA sequences of humans are so similar to those of chimpanzees, scientists have long speculated that differences in the activity levels of particular genes, otherwise known as gene expression, and, as a result, the amounts of particular proteins cells produce, are what distinguish humans from chimpanzees. The recent sequencing of the human genome has led to the development of “gene chips” that enable researches to examine the expression levels of thousands of genes at a time as well as compare expression levels in different species.

Using gene chips to compare samples of the cerebral cortex of humans, chimpanzees and rhesus monkeys, the research team at the Salk, the Yerkes Center and UCLA identified 91 genes that are expressed in different amounts in humans compared to the other primate species. Upon further study, the team observed 83 of these genes showed higher levels of activity in humans, and as a result, regulated neural activity.

“When we looked at other tissues, such as heart and liver, we found nearly equal numbers of genes showing higher or lower levels of expression in humans as compared to chimpanzees and rhesus,” said Todd Preuss, PhD, associate research professor of neuroscience at the Yerkes Research Center. “The changes in gene activity in the cortex suggest increases in the rate of brain activity, providing a basis for the evolution of the enhanced cognitive abilities in humans.”

In addition to finding changes in activity-related genes, the researchers found the human brain shows increased expression of genes that protect against activity-related damage. This finding may help explain why humans have the potential to live decades longer than other primates, but also why humans are especially vulnerable to age-related, neurodegenerative diseases, such as Alzheimer’s disease.

“It is probable that the combination of long lifespan and high neural activity makes humans particularly vulnerable to neurodegenerative disease,” said Mario Caceres, PhD, a postdoctoral fellow now at Emory University and lead investigator on the study. “Activity-related damage accumulates with age and has the potential to cause catastrophic breakdown late in life. By understanding how humans protect their brains from activity-related damage, we hope to better understand why those mechanisms fail.”

The Yerkes National Primate Research Center of Emory University is one of eight National Primate Research Centers funded by the National Institutes of Health. The Yerkes Research Center is a multidisciplinary research institute recognized as a leader in biomedical and behavioral studies with nonhuman primates. Yerkes scientists are on the forefront of developing vaccines for AIDS and malaria, and treatments for cocaine addiction and Parkinson’s disease. Other research programs include cognitive development and decline, childhood visual defects, organ transplantation, the behavioral effects of hormone replacement therapy and social behaviors of primates. Leading researchers located worldwide seek to collaborate with Yerkes scientists.

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We acknowledge support of the National Institute of Mental Health and the James S. McDonnell Foundation.