What Makes Us Different?
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What causes changes in both the dark matter and the genes themselves
as one species evolves into another is random mutation, in which
individual base pairs—the "letters" of the genetic alphabet—are
flipped around like a typographical error. These changes stem from
errors that occur during sexual reproduction, as DNA is copied and
recombined. Sometimes long strings of letters are duplicated,
creating multiple copies in the offspring. Sometimes they're deleted
altogether or even picked up, turned around and reinserted backward.
A group led by geneticist Stephen Scherer of the Hospital for Sick
Children in Toronto has identified 1,576 apparent inversions between
the chimp and human genomes; more than half occurred sometime during
human evolution.
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When an inversion, deletion or duplication occurs in an unused portion of the genome, nothing much changes—and indeed, the human, chimp and other genomes are full of such inert stretches of DNA. When it happens in a gene or in a functional noncoding stretch, by contrast, an inversion or a duplication is often harmful. But sometimes, purely by chance, the change gives the new organism some sort of advantage that enables it to produce more offspring, thus perpetuating the change in another generation.
WHAT THE APES CAN TEACH US
A striking example of how gene duplication may have helped propel us away from our apelike origins appeared in Science last month. A research team led by James Sikela of the University of Colorado at Denver and Health Sciences Center, in Aurora, Colo., looked at a gene that is believed to code for a piece of protein, called DUF1220, found in areas of the brain associated with higher cognitive function. The gene comes in multiple copies in a wide range of primates—but, the scientists found, humans carry the most copies. African great apes have substantially fewer copies, and the number found in more distant kin—orangutans and Old World monkeys—drops off even more.
Another discovery, first published online by Nature two months ago, describes a gene that appears to play a role in human brain development. A team led by biostatistician Katherine Pollard, now at the University of California, Davis, and Sofie Salama, of U.C. Santa Cruz, used a sophisticated computer program to search the genomes of humans, chimps and other vertebrates for segments that have undergone changes at substantially accelerated rates. They eventually homed in on 49 discrete areas they dubbed human accelerated regions, or HARs.
The region that changed most dramatically from chimps to humans, known as HAR1, turns out to be part of a gene that is active in fetal brain tissue only between the seventh and 19th weeks of gestation. Although the gene's precise function is unknown, that happens to be the period when a protein called reelin helps the human cerebral cortex develop its characteristic six-layer structure. What makes the team's research especially intriguing is that all but two of the HARs lie in those enigmatic functional noncoding regions of the genome, supporting the idea that much of the difference between species happens there.
SEX WITH CHIMPS?
Comparisons of primate genomes have also led to an astonishing, controversial and somewhat disquieting assertion about the origin of humanity. Along with several colleagues, David Reich of the Broad Institute in Cambridge, Mass., compared DNA from chimpanzees and humans with genetic material from gorillas, orangutans and macaques. Scientists have long used the average difference between genomes as a sort of evolutionary clock because more closely related species have had less time to evolve in different directions. Reich's team measured how the evolutionary clock varied across chromosomes in the different species. To their surprise, they deduced that chimps and humans split from a common ancestor no more than 6.3 million years ago and probably less than 5.4 million years ago. If they're correct, several hominid species now considered to be among our earliest ancestors—Sahelanthropus tchadensis (7 million years old), Orrorin tugenensis (about 6 million years old) and Ardipithecus kadabba (5.2 to 5.7 million years old)—may have to be re-evaluated.
And that's not the most startling finding. Reich's team also found that the entire human X chromosome diverged from the chimp's X chromosome about 1.2 million years later than the other chromosomes. One plausible explanation is that chimps and humans first split but later interbred from time to time before finally going their separate evolutionary ways. That could explain why some of the most ancient fossils now considered human ancestors have such striking mixtures of chimp and human traits—some could actually have been hybrids. Or they might have simply coexisted with, or even predated, the last common ancestor of chimps and humans.
All of that depends in part on the accuracy of fossil dating and the reliability of using genetic variation as a clock. Both methods currently carry big margins of error. But the more primate genomes that geneticists can lay side by side, the more questions they will be able to answer. "We have rough sequences for humans, orangutans, chimps, macaques," says Eric Lander, director of the Broad Institute and a leader of the research team that decoded the chimpanzee genome. "But we don't have the entire gorilla genome yet. Lemurs are coming along, and so are gibbons."
DECODING NEANDERTHALS
Also coming along, thanks to two independent teams of researchers, is the genome of the closest relative of all: the Neanderthal. Ancestors of Neanderthals first appeared some 500,000 years ago, and for a long time it was a toss-up whether that lineage would outlive our own species, at least in Europe and western Asia—or whether, bizarre as it seems today, they would both survive indefinitely. The Neanderthals held out for hundreds of thousands of years. A discovery published online by Nature last month suggests Neanderthals may have made their last stand in Gibraltar, on the southern tip of the Iberian Peninsula, surviving until about 28,000 years ago—and possibly even longer.
The Neanderthals weren't nearly as primitive as many assume, observes Eddy Rubin, director of the Department of Energy's Joint Genome Institute in Walnut Creek, Calif. "They had fire, burial ceremonies, the rudiments of what we would call art. They were advanced—but nothing like what humans have done in the last 10,000 to 15,000 years." We eventually outcompeted them, and the key to how we did so may well lie in our genes. So two years ago, Svante Paabo, the man who deconstructed the FOXP2 language gene and has done considerable research on ancient DNA, launched an effort to re-create the Neanderthal genome. Rubin, meanwhile, is tackling the same task using a different technique.
The job isn't an easy one. Like any complex organic molecule, DNA degrades over time, and bones that lie in the ground for thousands of years become badly contaminated with the DNA of bacteria and fungi. Anyone who handles the fossils can also leave human DNA behind. After probing the remains of about 60 different Neanderthals out of the 400 or so known, Paabo and his team found only two with viable material. Moreover, he estimates, only about 6% of the genetic material his team extracts from the bones turns out to be Neanderthal DNA.
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