12 Apr 2002

The obvious differences between humans and our closest relatives, the chimpanzees, belie the fact that our genomes differ by just over one percent. That most of those differences probably occur in non-coding regions led Marie-Claire King and Alan Wilson to propose, in 1975, that changes in protein concentration, as opposed to changes in protein structure, may be what separates humans from their cousins. Could this be why chimpanzees do not get Alzheimer's disease, or malaria? If borne out by experimental evidence, this hypothesis could help us understand our predilection for such diseases.

Svante Pääbo from the Max-Plank-Institute for Evolutionary Anthropology in Leipzig, Germany, together with colleagues in the USA and the Netherlands, has addressed the hypothesis by comparing human and chimp mRNA expression and proteome profiles. Their report appears in today's Science.

Their results suggest that the human brain has evolved more rapidly than other tissues. First, using Affymetrix chips, they conducted pairwise comparisons of the expression levels of 12,000 different mRNAs from brain and liver. The differences were used to make an overall distance tree with human, chimpanzee, and orangutan branches. It turns out that the evolutionary distance between human and chimpanzee brains is twice that found for their livers. By contrast, the same experimental regimen applied to three species of mice, which have similar overall genome differences as the three primates, had almost identical distances between liver and brain. The data suggest that it may be transcript or protein levels that separate us from the chimps.

To examine that idea, Pääbo et al. used 2D polyacrylamide gels to compare human and chimpanzee brain proteomes. They found that qualitative differences between the two, such as shifts in migration patterns, were similar to those between two species of mice, but that quantitative differences were six-fold higher between humans and chimps.

The next challenge will surely be to identify the proteins made in such vastly different amounts. Pääbo and colleagues identified some of them; curiously, they could all be classified as housekeeping enzymes, including aldose reductase, carbonic dehydratase, and malate dehydrogenase.—Tom Fagan