he genetic mechanism that through millennia of evolution
has created plump and juicy fruits and vegetables could also
be involved in the proliferation of human cancer cells.
Plant
biologists and computer scientists at Cornell University have
essentially made a direct genetic connection between the evolutionary
processes involved in plant growth and the processes involved
in the growth of mammalian tumors.
Studying the
genetic map of the tomato (Lycopersicon esculentum), the
researchers found a "plumping" characteristic in a
single gene called ORFX traits that are expressed early in the
plant's floral development. The protein sequence obtained from
the gene was predicted by computational data to be similar to
the human oncogene c-H-ras p21, suggesting a common mechanism
in the cellular processes leading to large, edible fruit in plants
and cancer in humans. The research is detailed in the July 7
issue of Science.
"We're
beginning to understand that there are very common mechanisms
that create life," says Steven D. Tanksley, Cornell Liberty
Hyde Bailey Professor of plant breeding and the lead author of
the research paper. "This is a case where we found a connection
between agricultural research in how plants make edible fruit
and how humans become susceptible to cancer. That's a connection
nobody could have made in the past.
"In this
era of genomics, many people are looking at divergent organisms,
and we're starting to realize connections we never imagined."
The discovery
springs from the Cornell researchers' attempts to identify the
remote evolutionary changes that led to the bountiful produce
associated with modern agriculture. Tanksley explains that wild
fruit and vegetable varieties were not always fit for human consumption.
Usually, they were too scrawny to provide much nourishment. But
over millennia, not only did humans cross plants, but the plants
also crossed themselves. Thus, many varieties became fleshy enough
to eat.
Corn kernels
were not originally succulent, and wild tomatoes looked more
like red blueberries. "When you see a beautiful ear of corn,
you're actually looking at a gross exaggeration of the corn's
real anatomy. Tomatoes and all other fruits and vegetables show
the same thing, compared with their ancestors. They have gross
exaggerations of the specific particular parts of their anatomy
- their fruit for example valued by humans," says Tanksley.
If not for
this mechanism, humans would not have developed beyond the hunter-gatherer
stage, and modern civilizations would not have been born. "We're
now codepen-dents with domesticated fruits and vegetables. Without
them, we can't sustain ourselves, and without us the domesticated
plants can't sustain themselves, either," says Tanksley.
"The humans and the plants have been caught up in a dance
of coevolution."
The Cornell
researchers were able to peer into the primeval development of
food with the aid of computer science. They found a genetic quantitative
trait locus, or QTL (the location of specific characteristics
on genes), involved in the evolution and domestication of a tomato
from small berries to what has become a large fruit. The ORFX
gene, located at fw2.2 on the plant's DNA, changes fruit weight
by up to 30 percent. The researchers say this gene is a key to
domesticating wild plants.
The discovery
might have taken decades if the researchers had used conventional
methods. After obtaining the nucleotide sequence from the gene,
which in turn provided the protein sequence, Tanksley collaborated
with Ron Elber, Cornell professor of computer science and acting
director of the Center for Parallel Processing Resources for
Biomedical Scientists at Cornell. Using a computational biology
program developed at the Cornell Theory Center, the scientists
created a three-dimensional structure from the protein sequence.
The software they used is called the Learning, Observing and
Outputting of Protein Patterns (LOOPP), which matches sequences
and protein structures.
Elber and
researcher Jaroslaw Meller matched the novel tomato sequence
with known three-dimensional protein shapes and found a hit.
Using as a template the structure of the ras (human oncogene)
protein, they were able to identify some of the protein's specific
chores. "Putting the protein into 3-D shape gave us guidelines
for what to look for, and to see the critical amino acids,"
says Elber. "Without any hints, it is difficult."
The algorithm
developed by Meller and Elber at Cornell is exceptionally efficient.
It identified the tomato gene in less than a minute.
Says Tanksley:
"It's astounding this kind of research could be done at
the speed at which it was done. This would have been impossible
a few years ago."
The research
was funded by the National Research Initiative Cooperative Grants
Program, the US Department of Agriculture Plant Genome Program,
the National Science Foundation, the Binational Agriculture Research
and Development Fund and the National Institutes of Health National
Center for Research Resources.
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