Humans and chimpanzees have in common more than 98 percent of DNA and 99 percent of genes. Yet, in looks and behavior we are very different from them. For more than 30 years--well before either the human or chimpanzee genome had been sequenced--scientists have speculated that this might be due to the way that the common genes express themselves rather than differences in the genes themselves. A new comparison published in Nature seems to prove that theory.

Geneticist Yoav Gilad of the University of Chicago and his colleagues used a new technique to examine the genes in the liver cells of four primates: humans, chimpanzees, orangutans and macaques. The researchers were able to compare more than 900 genes for each of the four and assess how they differed in terms of expression. More than half--60 percent--did not vary at all; the researchers found the same levels of mRNA--the molecule that links a gene and the protein it helps build--in all four for most genes. But 19 genes showed significant shifts in expression between humans and apes.

"When we looked at gene expression, we found fairly small changes in 65 million years of the macaque, orangutan and chimpanzee evolution," Gilad explains. "[This was] followed by rapid change, along the five million years of the human lineage, that was concentrated on these specific groups of genes."

Nearly half of the genes that had been pushed to express themselves more in humans involved transcription factors--gene-encoded proteins that control the expression of other proteins. By slightly changing these master genes, evolution could have an outsized effect on overall expression without as much chance of negative mutations, Gilad says. "I don't think our results reveal a novel mechanism," he adds. "But they are the first empirical demonstration in higher primates that evolution may often work through changes in gene regulation."

Gilad speculates that the relatively rapid alterations in human liver genetics might be the result of ongoing changes in diet, such as growing reliance on cooked food. "Perhaps something in the cooking process altered the biochemical requirements for maximal access to nutrients as well as the need to process the natural toxins found in plant and animal foods."

The finding has implications for medicine as well as evolutionary theory: nine of the 100 most stable genes have been linked to cancer when altered. "These findings suggest that focusing on genes with conserved expression levels among primates may be helpful in identifying promising candidates for disease-association studies," the researchers write. It also sheds some light on how two species--humans and chimpanzees--that share so many genes can be so different.