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Emerging "R&D" Pattern in Genes
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
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
"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
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
"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
"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,"
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
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