A Clue to Why Chimps,
People Differ So Much
Despite Similar DNA
March 26, 2004; Page B1
If a chimpanzee were one of those puzzles on the back of a children's cereal box -- the ones where you're shown a shape composed of a dozen toothpicks and asked to move only four of them to form, say, a star -- the instructions would go something like this: Start with the thousands of genes in the chimp genome.
Change, delete or add only a few hundred so that you now have the full genetic instruction manual for making a human.
Misapprehensions to the contrary, humans did not evolve from chimps. Both species evolved from a common, apelike ancestor. Yet since the two lineages diverged some five million years ago, the genetic changes have been few. Chimps are our closest living relative.
Their genomes are about 97% identical to ours. How, then, can so few genetic differences account for our language-using, cathedral-building, opera-writing and computer-inventing?
Yesterday, scientists announced that they have taken a big step toward solving that mystery. Writing in the journal Nature, they report the discovery of the first genetic difference between humans and chimps that produces a clear functional difference. Making the finding more tantalizing, the mutation occurred at roughly the same time that humanlike traits first appeared in the fossil record. Yet the gene has nothing to do with intelligence or other traits, at least not directly, and therein lies a lesson.
Back when the human genome project was going fast and furious, churning out DNA sequences by the thousands every day, Hansell Stedman of the University of Pennsylvania was looking for any genes that might affect muscle proteins (a surgeon and molecular geneticist, his specialty is muscle diseases). The most common muscle proteins are myosins; humans have about 10 genes that produce one or another myosin.
Compared with other myosin genes, Dr. Stedman found, one such gene (called MYH16) was missing two "base pairs," the molecular units that make up DNA. At first he figured the missing base pairs was a rare mutation. But the genome of every human he and his colleagues studied -- Africans and South Americans, Europeans and Japanese -- has the mutation.
With more sleuthing, they found the last thing they expected in a little project on muscle disease. Macaques and at least six other non-human primates have a nonmutated version of MYH16, which gives them huge jaw muscles. Humans' mutated gene keeps us from making this jaw-muscle protein, and so we have smaller jaws.
But we also have something else. The larger the muscle, the more bone is required to anchor it. As a result, gorillas and macaques with big jaw muscles also have extra bone on top of their skulls. "The way the bone is laid down, the cranium can't grow," says Dr. Stedman. But in humans, who don't need extra skull bone, the skull keeps growing. And so does the brain inside it. Only half in jest, the scientists call the muscle mutation RFT, "room for thought."
"Something going on outside the brain turns out to have a very important impact on what's going on inside it," says Dr. Stedman. "This was a surprise to all of us."
Using standard molecular genetics, the Penn team infers that the muscle-minimizing mutation appeared 2.4 million years ago. That is right before fossils of human ancestors start having larger, more human-like skulls. Before then, human ancestors such as Paranthropus and Australopithecus had large jaws and small skulls filled with small brains. Although the jaw-muscle mutation was surely not the only, and maybe not even the most important, genetic change that created the human species, it likely helped unleash the brain growth that makes humans human.
The Penn discovery, writes developmental biologist Pete Currie of the Victor Chang Cardiac Research Institute, Sydney, Australia, in a commentary in Nature, "suggests that the genetic basis of human evolution can and will be defined."
That will require a point-by-point comparison of the human and chimp genomes. The sequencing of the human genome was finished last April. The chimp genome is coming along; the first draft was released in December.
Now comes the needle-in-a-haystack part. Ajit Varki of the University of California, San Diego, guestimates that there could be 40 million places where the base pairs of the human genome differ from those of the chimp. That's out of 3.1 billion base pairs.
So far, researchers have identified a handful of genetic differences between humans and chimps. A gene involved in language development seems unique to humans, researchers led by Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Liepzig, Germany, reported in 2002. And last year he found that humans have many fewer genes for olfactory receptors, molecules that detect aromas, than great apes do.
If the jaw-muscle protein is any indication, though, scientists would do well to look beyond the obvious suspects for the genetic changes that produced humans from ape-like ancestors. "The myosin gene sat around for years" without anyone realizing its significance, says Dr. Stedman. "Some of the most fascinating genes accounting for the differences between humans and apes might also be lying around."
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