Missing bits of DNA may define humans

Genetic information lost along the way led to bigger brains, spineless penises

In evolution as on reality TV, sometimes the biggest loser is really a winner.

DELETED DNA Humans have lost pieces of influential DNA, impacting the activity of genes that, in mice, help keep brains small (left; blue spots indicate gene activity in developing mouse embryo) and form penile spines (right). The absence of that genetic material may have led to bigger brains and longer copulation times in humans, new research suggests. Alex Pollen, Philip Reno

Losing 510 chunks of DNA may have enabled humans to develop bigger brains, spineless penises and other human traits, researchers from Stanford University and their colleagues report in the March 10 Nature.

The research is the latest attempt to find genetic factors that make humans human. Previously researchers have searched for genes that humans have but other species do not, but the new study turns that approach on its head, looking instead for pages redacted from the human genetic instruction book during the course of evolution.

“This is a clever thing to do and as so often with good ideas, seems almost obvious in hindsight,” says Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Looking for missing DNA that could shape human traits was something of a no-brainer for Stanford researchers David Kingsley and Gill Bejerano. Kingsley, a developmental geneticist, had previously discovered that stickleback fish species can shed prominent pelvic spines by losing a bit of DNA involved in growing limbs and other appendages (SN: 1/31/09, p. 26).

The team looked at the genetic blueprints of humans, chimpanzees and macaques to see if humans were missing any pieces found in the other two species.

Indeed, humans lack many chunks of DNA that chimps, macaques and mice all seem to share — at least 510 different bits. Most are also missing from Neandertals, suggesting that the pieces were lost sometime between 500,000 and 6 million years ago.

Only one of the missing bits contained an actual gene. The rest of the absent genetic instructions may be important switches for turning on genes. Such switches, known as enhancers, can be located far from a gene but still govern when and where the gene is flipped on during development.

Humans and chimps have roughly the same set of genes, and yet have clear physical and behavioral differences. Some scientists have reasoned that changing the way genes are used — by turning a gene on or off in a particular tissue or during a phase of development — may be a way to evolve new characteristics without damaging important genes. Adding or deleting enhancers is one way to regulate gene activity.

“It’s probably the best way to develop new functionality in the short run,” says David Haussler, a Howard Hughes Medical Institute investigator at the University of California, Santa Cruz.

Because most of the missing chunks of DNA don’t contain genes, it is difficult to say exactly what the pieces are supposed to do. The Stanford team used “a very clever computational analysis” to tease out a couple of pieces of DNA that might have clear-cut functions, Haussler says.

One of the bits is near a gene that controls production of an androgen receptor, a protein that detects testosterone. The piece of DNA missing in humans is an enhancer for the gene, which controls the production of facial sensory whiskers and small spines on the penises of both chimps and mice, the researchers found. Since humans don’t have the enhancer, the gene is not turned on, and sensory whiskers and penile spines fail to develop.

In some mammals, penile spines are prominent and may help males achieve ejaculation quickly. “The key to reproductive success is impregnation, and the faster you can achieve that, the better,” says Owen Lovejoy, a biological anthropologist at Kent State University in Ohio. But even though the loss of the spines makes copulation last longer, it hasn’t hurt the reproductive success of humans, he says. Longer copulation times may help cement bonds between mating partners, which Lovejoy says has been a key to humans’ evolutionary success.

Another missing enhancer identified in the new study may help explain the evolution of human brain size. The enhancer lies next to a tumor-suppressing gene called GADD45G, which normally reins in cell growth so that cancer doesn’t develop. In mice and chimps, the enhancer DNA turns the gene on in the brain. Because humans lack the enhancer, the gene is not turned on in the brain and brain cells may proliferate, possibly contributing to bigger brains.

The enhancer probably isn’t the only thing that led to humans’ increased brain power, Kingsley says. “There’s no way changes in a single gene are going to produce all the interesting changes that led to the human brain.”

Removing the enhancer from mice may help researchers learn just how much brain growth the missing piece of DNA is responsible for, he says.

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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