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New Genes, New Brain

A bevy of genes known to be active during human fetal and infant development first appeared at the same time that the prefrontal cortex—the area of the brain associated with human intelligence and personality—took shape in primates.

Oct 19, 2011
Cristina Luiggi

WELLCOME IMAGES, MARK LYTHGOE & CHLOE HUTTON

A bevy of genes known to be active during human fetal and infant development first appeared at the same time that the prefrontal cortex—the area of the brain associated with human intelligence and personality—took shape in primates, a new study published yesterday (October 18) in PLoS Biology found. The timing suggests that the new genes may have been intimately tied to the evolution of the human brain.

“This is one of the first studies to look at the role of completely novel genes” in primate brain development, said Eric Vallender, a neurogeneticist at Harvard Medical School who was not involved in the study. Previous research has focused on relatively old genes (i.e. genes that are conserved across the animal kingdom and beyond), he said, with a particular focus given to identifying changes in their protein products as well as overall changes to gene regulation. The new study’s emphasis on the addition of new genes to the genetic repertoire could yield new insights into the genetic changes that led to the modern human brain, he added.

By comparing the order and orientation of genes along chromosomes across multiple mammalian species—spanning humans to mice—the researchers, led by University of Chicago evolutionary geneticist Manyuang Long, noticed several striking patterns.

First, genes that arose around the time that mammals first appeared (a little over 200 million years ago) tended to be active in the fetal human neocortex, a brain region largely unique to mammals that houses the prefrontal cortex. Furthermore, out of the 1,000 or so genes found only in primates, 251 were upregulated in the developing prefrontal cortex, which evolved right after the primate lineage diverged from the rest of the mammals around 60 to 80 million years ago. Finally, 54 of the 280 genes found to be unique to humans were also highly expressed in the developing prefrontal cortex, which grew considerably in humans after the human chimpanzee lineages broke off around 5 to 7 million years ago. (The human prefrontal cortex is six times larger than the chimpanzee’s.)

“We were very shocked that there were that many new genes that were upregulated in this part of the brain,” said Long, who added that he was also taken aback by synchronicity of the origin of the genes and the development of novel brain structures. It seems that around the same time that the neocortex and the prefrontal cortex arose, and then expanded in humans, a large collection of genes also popped up.

“You always have the correlation versus causation question,” Vallender cautioned. “But it’s very consistent that these genes were all arising at the same time as these new anatomical structures that we know are very important in cognition and behavior.”

The researchers also determined that the majority of these new genes underwent strong positive selection in humans, further supporting the hypothesis that the genes contributed to the evolution of important functions in the brain.

“All of this is circumstantial evidence that supports this more broad idea that these new genes have something interesting to say about primate-specific or human-specific brain function,” Vallender said.

Y.E. Zhang et al., “Accelerated recruitment of new brain development genes into the human genome,” PLoS Biology, doi:10.1371/journal.pbio.1001179, 2011.

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