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The Frustrating Hunt for the Genes That Make Us Human

Researchers are finding many genes unique to our species, but so far they reveal little about our most human traits.
What makes us so different from these chumps? (Photo: tambako/Flickr)

What makes us so different from these chumps? (Photo: tambako/Flickr)

Genes aren't the whole story when it comes to understanding why, as individuals, we are the way we are. Non-genetic factors in our social and physical environment clearly influence our behavior, our physical appearance, and our health. But that's not true when we consider our species as a whole. The reason why we differ from other animals—why we learn to speak fluent English or do algebra, while chimpanzees don't—is entirely genetic.

When you consider the dramatic biological differences between humans and chimps, our genes are surprisingly similar. Scientists began comparing human and chimp genes in the 1960s, and they were shocked to discover that we are almost genetically identical. "The genetic distance between humans and the chimpanzee is probably too small to account for their organismal differences," wrote University of California-Berkeley researchers Mary-Claire King and Allan Wilson in a groundbreaking paper published in 1975. When the chimp genome was finally published 30 years later, these early findings were confirmed. Human and chimp DNA is 97 to 98 percent identical.

"The genetic distance between humans and the chimpanzee is probably too small to account for their organismal differences."

Knowing this, it's difficult not to ask the obvious question: How exactly does that two percent of our DNA make us human and not chimp? By studying this small fraction of our genome, researchers are searching for those parts of our DNA that are responsible for distinctive human traits, particularly ones linked to our powerful brains, including language, advanced reasoning, and unique social behaviors.

Thanks to the completion of genome projects for humans, chimps, and dozens of other mammals within the past 15 years, researchers have been able to search directly for uniquely human DNA, by comparing our genome to that of other species. They have discovered a few hundred new genes and several thousand regions of our genome that show signs of recent, rapid evolution. Not surprisingly, many of these new genes and rapidly evolving genomic regions appear to be associated with brain function. In some cases, brain-linked genes that have evolved rapidly make us vulnerable to psychiatric disorders like schizophrenia and autism. This suggests that evolutionary innovations in an organ as fantastically complex as the human brain often strike a precarious balance between new cognitive functions and disease.

The results of the hunt for human-specific genes are fascinating, but at this stage, they are more frustrating than enlightening. A study published in late March illustrates why. A team of researchers from the Max Planck Institute in Dresden, Germany, reported that they had discovered a human-specific gene that is active in the neocortex, which is the greatly enlarged part of the brain that is responsible for higher cognitive functions. This gene, with the unwieldy name of ARHGAP11B, is a near-duplicate of a different gene that is common to all animals. We picked up this new gene some time after our evolutionary lineage split off from chimps six million years ago, but before we diverged from Neanderthals—ARHGAP11B is present in the Neanderthal genome as well.

Because it is unique to humans and active in the neocortex, ARHGAP11B is exactly the kind of gene that researchers expect played an important role in the evolutionary development of distinct cognitive traits. To test its function, the scientists transferred the gene into mouse embryos and looked for its effects on the mouse brain. The results were dramatic: ARHGAP11B caused critical cells in the small mouse neocortex to multiply many times more than they typically do. The result was a thicker neocortex—in other words, the researchers found a human gene that makes a mouse brain grow bigger. The gene also caused the normally smooth mouse neocortex to begin folding inwards, which is striking because a highly folded neocortex is a distinctive feature of human brains.

This exciting result shows how one particular uniquely human gene may contribute to the distinctive features of our brains. And yet the researchers' main conclusion, that ARHGAP11B "amplifies basal progenitors and is capable of causing neocortex folding in mice,” doesn't sound like a very profound answer to the big question of how we acquired language, reasoning, or any other distinctly human cognitive functions. The effects of this one gene on mouse brains are suggestive, but for the time being, all we have are a few molecular details. The big picture is still missing.

And it's hard to envision how we will ever see the big picture with this approach. We're very good at using our knowledge of genes to explain the molecular processes that happen inside cells, but we don't know how those processes produce full human traits. It's unlikely that we’ll understand this any time soon, because to explain human traits we need to understand how genes build cells, how cells build brains, and, finally, how a physical organ like our brain produces our distinctive mental traits. All of which are very tall orders.

This means that, as compelling as it sounds, asking how our unique genes make us human is the wrong question. As the biologist Morris Goodman argued nearly two decades ago—before the hunt for human genes really took off—the idea that "what makes us human resides in the 1.5% difference in genomic DNA that separates us from chimpanzees ... is far too narrow." Goodman noted that "some of the most striking human features, such as greatly enlarged brains and prolonged childhoods in social nurturing societies, have deep roots in our evolutionary history."

While identifying the genes that are unique to our species is an important first step, to understand their role we need to learn much more about exactly where we differ from chimps and where we don’t—something that is still an active area of research. Without that knowledge, studying unique human genes in isolation will tell us little about what we really want to know: why nearly all humans easily learn to speak, write, and do math, while even the smartest chimps don't.

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