One gene in particular—SRGAP2—plays a role in how brain cells migrate. It is found widely in mammals of all sorts, from mice to humans. In the great apes, the more archaic form of SRGAP2 results in a relatively slow spread of neurons throughout the brain. Twice in the ancient past, however, SRGAP2 was duplicated, first about 3.4 million years ago and then again around 2.4 million years ago. The second duplication occurred right around the time when the genus Homo separated from Australopithecus. It appears that as a result of these duplications, brains in the Homo lineage—including our own as Homo sapiens—are both large and complex in their number of neuronal connections and in their ability to process information.
A key piece of supporting evidence comes from recent discoveries of the role of SRGAP2 in the development of the human neocortex. When the distinctly human SRGAP2 variants are missing, normal human brain development is impaired. This research appears in two papers appearing May 3, 2012 in the journal Cell. According to one of the papers, “It is intriguing that the general timing of the potentially functional copies…corresponds to the emergence of the genus Homo from Australopithecus (2-3 mya). This period of human evolution has been associated with the expansion of the neocortex and the use of stone tools, as well as dramatic changes in behavior and culture.”
Caption: A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. Credit: Photo courtesy of The Scripps Research Institute Usage Restrictions: None
The uniquely human duplications work in a surprising ways, especially the second duplication. The original SRGAP2 remains present in humans today, along with the duplicated versions. The second duplication—SRGAP2C—has the effect of interfering with the original SRGAP2. The reason why SRGAP2C interferes with SRGAP2 rather than boosts it is because the duplicated version is incomplete—in other words, an advantageous copying error.
According to one of the studies, once SRGAP2C appeared about 2.4 million years ago, it created a “dominant negative interaction equivalent to a knockdown of the ancestral copy…The incomplete nature of the segmental duplication was, therefore, ideal to establish the new function by virtue of its structure,” acting in a way that was “instantaneous” in terms of evolution.
"This innovation couldn't have happened without that incomplete duplication," according to Evan Eichler, another leader in the research team. "Our data suggest a mechanism where incomplete duplication of this gene created a novel function 'at birth'."
Even though SRGAP2 duplications seem to play a significant role in distinguishing human beings from the apes, other duplications and mutations are very likely to be involved in the story of human evolution. "There are approximately 30 genes that were selectively duplicated in humans," said Franck Polleux, one of the lead researchers involved in the study, in a press release from the journal. "These are some of our most recent genomic innovations."
Rather than standard mutations, "episodic and large duplication events could have allowed for radical – potentially earth-shattering – changes in brain development and brain function," according to Eichler. For these reasons, this is one of the most intriguing areas for research into the origins of human intelligence.
Whether other duplications—including “incomplete duplications or erroneous copies—also explain our complex brains is something that will be discovered in the next few years.
But what is surprising and somewhat sobering, just based on this SRGAP2 discovery, is how our much-vaunted human uniqueness seems to hang on such a fine thread. If the SGGAP2 duplication is even partly responsible for our complex brains, should we think that our intelligence arose because of a copying error or an incomplete duplication? Is the rise of intelligence and consciousness—truly one of the great events in the story of cosmic evolution—really just based in part on a fluke of nature? Religious or not, hardly anyone is likely to think that thinking is sheer accident.
The papers, 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," appear in the journal Cell.