Public Release:  Networking slows down protein evolution, study reveals

Stanford University

A fundamental principle of biology is that all life evolved from a common microbial ancestor that appeared on Earth billions of years ago. This basic tenet of evolutionary theory has been affirmed by the recent flurry of genome maps showing that a wide variety of species - from yeast to roundworms to humans - carry thousands of virtually identical genes in their DNA.

Thanks to the current genomics revolution, biologists have new tools to document the minute changes a gene undergoes when it evolves from a simple organism to a more complex one. In a study published in the April 26 issue of the journal Science, researchers from Stanford and the University of California-Berkeley compared the genomes of a fungus and a worm - two very different species that share thousands of similar genes, which in turn produce thousands of similar proteins.

``There`s been a flood of genetic information recently,`` said Stanford graduate student Aaron E. Hirsh, lead co-author of the Science study. ``The question is, how do we make sense of it?``

In their Science study, Hirsh and his colleagues analyzed thousands of proteins shared by two organisms - the single-celled yeast, S. cerevisiae, and the more complex roundworm, C. elegans.

Proteins provide a wealth of information about an organism`s evolutionary history. Each protein consists of a chain of molecules called amino acids that are strung together in a specific order dictated by a specific gene.

The amino acid sequence varies in different organisms. For example, a bacterial protein is likely to contain slightly different amino acids than a corresponding human protein - even though both proteins carry out the same biological function in both organisms. These tiny differences in the amino acid sequence provide a record of how the protein changed in bacteria and people over billions of years of evolution.

Yeast and roundworms

Yeast and roundworms have been the subjects of intense international research efforts, which culminated in the complete mapping of the roundworm genome in 1996 and the yeast genome two years later. Using these and other genetic data, Hirsh and his coworkers looked at several factors that may have affected the rate of protein evolution in yeast and roundworms since they separated from their common ancestor about one billion years ago.

``Each gene encodes a protein,`` Hirsh explained. ``By comparing the proteins that yeast and roundworms have in common, we can infer how rapidly their genes evolved.``

He noted that yeast is a particularly good model for evolutionary research - not only because its DNA has been fully mapped, but also because of recent studies showing that many yeast proteins form interacting networks that allow them to communicate with one another inside the cell.

``How genes interact to form complex traits in an organism is a relatively new aspect of evolutionary theory,`` said Stanford biologist Marcus W. Feldman, co-author of the Science study.

He pointed out that yeast - a relatively simple fungus - has 6,000 genes; the roundworm 19,000; and humans, with all of our complexity, only 30,000 to 40,000.

``How do these species accomplish all they do with such a limited number of genes? The answer - protein interactions,`` added Feldman, the Burnet C. and Mildred Finley Wohlford Professor in the School of Humanities and Sciences.

By comparing the amino acid sequences in 2,235 yeast and roundworm proteins, Feldman and his team confirmed a prediction made more than 20 years ago: Proteins that interact with a large number of other proteins evolve at a slower rate than those with fewer protein-protein interactions.

``Proteins with more interactors evolve more slowly, not because they are more important to the organism, but because a greater proportion of the protein is directly involved in its function,`` the authors wrote in Science.

This study comes on the heels of a paper published in the journal Nature last October in which Hirsh showed that proteins necessary for the survival of roundworms and yeast also evolve at a slower rate than nonessential proteins.

According to the authors, many of the proteins and genes included in these studies also occur in people and one day may provide insights into inherited diseases and other aspects of human genetics.

``We can answer a lot of essential evolutionary questions with yeast that apply to the human genome as well,`` Feldman noted.


Other contributors to the Science study were lead co-author Hunter B. Fraser, formerly a Stanford undergraduate intern in the Feldman laboratory and now a graduate student at UC-Berkeley; and Lars M. Steinmetz and Curt Scharfe, postdoctoral fellows at the Stanford Genome Technology Center. The study was funded with a National Institutes of Health Program Project Grant.

COMMENT: Marcus W. Feldman, Biological Sciences (650) 725-1867;

EDITORS: The study, ``Evolutionary Rate in the Protein Interaction Network,`` appears in the April 26 issue of Science magazine. A copy can be obtained from the AAAS News & Information office in Washington, D.C., at (202) 326-6440 or

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