Researchers have discovered a gene duplication related to the human brain that may have been responsible for adaptive evolutionary changes leading from ancient primate ancestors to modern humans. According to the scientists who participated in the study, two gene duplications occurred that were related to brain development, an aspect of change that was key to the emergence of ancestral and, ultimately, modern humans.
"There are approximately 30 genes that were selectively duplicated in humans," said Franck Polleux, a study participant and expert in brain development at The Scripps Research Institute. "These are some of our most recent genomic innovations."
Polleux and Evan Eichler, who is a genome scientist at the University of Washington, focused on a key gene known as SRGAP2. This gene was apparently duplicated at least twice over the past four million years, once about 3.5 million years ago and again about 2.5 million years ago. But the second event involved only a partial duplication, resulting in a genetic innovation that may have helped launch evolutionary changes in brain development and the emergence of the human line from related primate ancestors. The occurrence appears to correspond with changes in the fossil record that suggest a transition from the human's Australopithecus ancestors (now extinct) to Homo, the genus which eventually led to modern humans. It also correlates with the time when the brains of human ancestors began to expand and more advanced cognitive abilities emerged.
Says Eichler, "this innovation couldn't have happened without that incomplete duplication. Our data suggest a mechanism where incomplete duplication of this gene created a novel function 'at birth'."
By mimicking the partial SRGAP2 duplication in mice, the researchers found that the change accelerated neuron migration and enabled new connections between neurons to form. By extension, Eichler and Polleux postulate that the duplication event may have resulted in dramatic variation in ancestral human evolutionary history, explaining, at least in part, the major differences between humans and primates, even though the overall genome sequences between humans and other primates are mostly the same.
The study results could potentially revolutionize the approach to studying genetic changes and the genetic makeup of humans as they relate to human evolution.
"We may have been looking at the wrong types of mutations to explain human and great ape differences," says Eichler. "These episodic and large duplication events could have allowed for radical – potentially earth-shattering – changes in brain development and brain function."
The research findings are also providing insights to understanding other neurodevelopmental disorders where neuronal connections are affected, such as autism, epilepsy and schizophrenia. The researchers refer to human cases with brain defects and symptoms that may be related to disruption of the ancestral SRGAP2.
The detailed results of the two studies* are published in the May 3rd issue of the journal Cell, a Cell Press publication.
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*Charrier et al.: "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation," and Dennis et al.: "Human-specific evolution of novel SRGAP2 genes by incomplete segmental duplication
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