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Emerging "R&D" Pattern in Genes
May Reduce Evolution's Risks

The genetic blueprint at the heart of life may be divided into "research and development" and "production" sections, according to an author of a new study in this week's "Science" that compares genetic material in yeast, roundworms, insects and humans.

The distinction may help shunt the random genetic changes that cause evolution onto areas of the DNA where such changes have a better chance of benefitting the organism (the "R&D" section) and away from areas where they would more likely harm it (the "production" section).

"The great paradox of evolution is that you have many established functions to maintain in an organism, and how can you be conservative about those functions while experimenting to discover new and possibly advantageous gene functions?" says Edward Hedgecock, biology professor at The Johns Hopkins University.

If it is confirmed, the theory could aid researchers in their efforts to analyze genetic information from humans and other species.

With support from the National Institutes of Health, Hedgecock and other researchers conducted an extensive computerized comparison of the sequence of genetic information, known as genomes, found in yeast, the roundworm C. elegans and other nematodes, the fruit fly Drosophila, and humans.

New species arise throughout evolution. Comparing their genomes can therefore provide "snapshots" of the development of DNA at various points in evolutionary history. Since portions of DNA are used as instructions for building proteins, researchers can compare the details of these "snapshots" to get a feel for when life first developed various proteins.

If, for example, a gene for a protein is common to yeast and to animals, Hedgecock explains, then the protein's birth date was before the emergence of multicellular organisms.

Hedgecock and his coauthors focused most of their attention on proteins involved in the creation of the exterior of the cell. Examples include the proteins that help cells stick to surfaces, proteins that help create a sheath that is the outermost boundary of a cell, and proteins that are emitted by cells.

Scientists grouped the proteins into families and "superfamilies."

"Proteins are in the same family if they have essentially the same modular organization along their length," Hedgecock explains. "They're made of the same parts in the same order. Superfamilies are a higher structural class, and that only means that the proteins share an individual domain, but they may differ--be unrelated--outside of that."

While noting that the human genome is not completely sequenced yet, researchers reported finding some families and superfamilies of proteins present in C. elegans and other roundworms that are absent in the human genome. Families and superfamilies, they concluded, are being created throughout evolutionary history.

"The big surprise, though, is evidence that old superfamilies can be remarkably stable alongside a new family being created," Hedgecock says. "The old idea was that all the genes of the genome were subject to similar mutational processes, so roughly speaking, the older you were as a gene family, the more opportunity you had to duplicate, to disperse in the genome, and to diverge from one another."

The very oldest superfamilies should be the largest, the most dispersed, the most diverged, and the fastest-growing in size, he explains. But the team's analysis found that once superfamilies are established, they can be very stable even if they're beside a dynamic, young expanding family of proteins.

By analyzing the organization of the genes, looking at the pattern of genetic material actually used to build proteins, and studying a database of genes with known mutations in C. elegans, the researchers found a pattern of two kinds of regions in the DNA: areas with long-established genes with advantageous properties, and areas where the DNA was being shuffled and rearranged.

"We speculate in the paper that this division may correspond to a division that scientists have noticed in cells that are in the process of dividing," Hedgecock says.

Dividing cells have to make an additional copy of the DNA they contain, a task that requires them to unpack DNA from structures known as chromosomes where it is stored. Scientists have noticed that some portions of the chromosomes appear to get more thoroughly unpacked than others. The portions of the genome that are incompletely unpacked might be more susceptible to mutational processes, Hedgecock theorizes, while the genes that have established value are in the fully open areas.

"The analogy to industry is that you separate your research and development facility from your production facility–if you ever were to combine those two activities, it might be a disaster," says Hedgecock.

Other authors on the paper included Harald Hutter of the Max-Planck-Institute for Medical Research in Heidelberg, Germany; and Bruce Vogel, an associate research scientist at Johns Hopkins. Additional authors came from the University of Toledo in Toledo, Ohio; Washington University in St. Louis; and the Max-Planck-Institute for Developmental Biology, also in Germany.


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