BioWorld International Correspondent
LONDON It is difficult to understand how humans and chimpanzees are so different, when their genomes differ by a mere 1.3 percent. Now researchers in Europe and the U.S. have confirmed what was first hypothesized 25 years ago that the differences might be due to differences in gene expression.
The study, led by Svante P bo of the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany, found that there was a greater difference in gene expression patterns between the brains of humans and those of chimpanzees, than between the livers or white blood cells of those species. This suggests, the researchers said, that the human brain may have undergone accelerated evolutionary change.
P bo and his colleagues report their findings in a paper in the April 12, 2002, Science titled “Intra- and Interspecific Variation in Primate Gene Expression Patterns.” The paper also reports a preliminary study that identified significant differences in the amounts of various proteins present in the brains of humans and chimpanzees.
New insights into diseases such as cancer, AIDS, malaria and Alzheimer’s disease, which affect humans but not chimpanzees, are likely to flow from the discovery, the researchers predict.
Wolfgang Enard, who is joint first author of the paper, told BioWorld International, “This is the first time that a new type of biology, and particularly the technology of using DNA microarrays, has been applied to evolutionary questions. People have compared genomes and DNA sequences before, but no one has previously compared RNA transcripts or protein expression between different species.”
The study marks, he suggested, the dawn of a new era of evolutionary genomics. “The question of what makes a human a human and a chimp a chimp will be answered in different ways by a philosopher and by a behavioral biologist. Now molecular biologists can also give their view,” Enard said.
Enard, who is working for his Ph.D. in P bo’s laboratory, explained that the study came about when the team decided to apply the technology of DNA microarrays to the question of the evolutionary relationship between humans and chimps.
They obtained brain tissue from chimpanzees and other primates that had died from natural causes at the Yerkes Primate Center in Atlanta, and from humans. Working with collaborators at the University of California at San Diego, they isolated messenger RNA from the brain tissue, labeled it and looked to see if it would hybridize with spots of DNA from about 12,000 human genes presented on a microarray.
Enard said, “We had to study several individuals, both chimp and human, otherwise we would not have known whether the differences we were observing were down to individual variation or the difference between species. So we studied three chimps and three humans, and although we found substantial differences between individuals, we also saw a big difference between humans and chimps.”
To determine whether it had been humans or chimps that had changed their level of expression, the team did a parallel study on a sample of brain tissue from an orangutan, a third species distantly related to both chimps and humans. “We found that the orangutan’s brain resembled that of the chimp, which makes it more likely that it was the humans who had changed, rather than the chimpanzees,” Enard said. However, these differences were much less marked in the livers and white blood cells of the humans, chimps and orangutans.
As a double-check on their experiments, the researchers conducted a similar study on three species of mice that are about as closely related to each other as humans, chimpanzees and orangutans. Here, they found that the differences they observed were distributed equally in liver and brain.
“This may be evidence that faster evolution of the human brain has taken place,” Enard said.
Ajit Varki, professor of medicine and cellular and molecular medicine at the University of California at San Diego School of Medicine, and one of the authors of the Science paper, said: “With an understanding of the differences between humans and chimpanzees, we may be able to learn more about the genetics underlying diseases that seem to harm humans but not chimpanzees.” For example, he said, although chimps can become infected with HIV, they rarely develop AIDS, and even when injected with forms of malarial parasites that frequently kill humans, they develop only mild malaria.
Enard added that although scientists can learn a great deal by comparing humans and chimpanzees, the study reinforces the view that chimpanzees are a poor substitute for humans when it comes to carrying out medical research.
The group is planning more detailed studies of comparative protein expression in the brains of humans and chimpanzees. It also wants to find out if the differences observed in mRNA transcripts hold true for different regions of the brain. “For example,” Enard said, “you might imagine that more conserved parts of the brain such as the brain stem would not change as much, whereas you would be able to observe a much greater difference in regions of the brain that had undergone much greater changes in function.”