Jim Barlow, Life Sciences Editor
217-333-5802; jebarlow@illinois.edu
12/13/05
CHAMPAIGN, Ill.
— Could vital information about many human diseases be deciphered
from genes inside freshwater flatworms?
A definitive yes is not the answer yet, but research at the University
of Illinois at Urbana-Champaign has provided an important advance for
pursuing both that idea and the biology of stem cells.
In a paper appearing online this week ahead of regular publication in
the Proceedings of the National Academy of Sciences, researchers report
the sequencing and analysis of 27,161 expressed sequence tags (ESTs)
of the sexually reproducing strain of the planarian Schmidtea mediterranea.
Not only were 66 percent of them similar to sequences already in public
databases, the researchers found 142 of 287 genes associated with human
diseases. Because the ESTs they studied represent only about one-half
of the total, “it seems likely that the vast majority of human
disease genes will have homologues in planarians,” the scientists
wrote.
“One of the striking things we found is that when we look at planarian
genes, we see a group that is conserved between planarians and mammals
that is not found in Drosophila or C. elegans,” said Phillip A.
Newmark, a professor of cell
and developmental biology at Illinois.
“We speculate that these conserved sequences may play roles in
processes such as long-term tissue maintenance and cell turnover that
are likely less important for short-lived organisms like nematodes and
insects,” wrote Newmark and colleagues.
Drosophila melanogaster and C. elegans (Caenorhabditis elegans) are
standard model invertebrates used in biology. “The fact that they
don’t have some of the genes that planarians share with mammals
says that planarians will be an important, complementary model for studying
gene function,” Newmark said.
On a more basic level, the work by Newmark and colleagues will aid the
planarian genome-sequencing project being done at Washington University
in St. Louis.
ESTs are short sequences of DNA produced by the reverse transcription
of messenger RNA into complementary DNA. Sequencing and categorizing
ESTs allow researchers to rapidly identify genes.
Previously sequenced ESTs came from asexual planarians.
Sexual planarians don’t develop reproductive structures until
after they’ve reached adulthood, when their stem cells go to work
in a process known as epigenetic germ cell specification. Asexual planarians
reproduce by transverse fission – by splitting into pieces and
regenerating; they do not develop reproductive structures.
Both planarian strains, however, can regenerate themselves when split.
By comparing the machinery of the two strains, basic knowledge about
stem and germ cell activity might be enhanced, Newmark said. “Many
of the genes in this collection are going to be important for studying
stem cell biology and regeneration,” he said.
The ESTs identified by Newmark’s team came from two developmental
stages of S. mediterranea. The 27,000-plus ESTs represent some 10,000
unique transcripts, or individual sequences of RNA. Of 53 genes linked
to reproduction, 87 percent were expressed in reproductive organs.
The research by Newmark’s team was done in collaboration with
the W.M. Keck Center
for Comparative and Functional Genomics at Illinois.
Co-authors were postdoctoral researcher Ricardo M. Zayas; Alvaro Hernandez,
assistant director for DNA services at the Keck Center; Bianca Habermann
of Scionics Computer Innovation in Germany; and doctoral students Yuying
Wang and Joel M. Stary.
The National Science Foundation, National Institutes of Health, and
Damon Runyon Cancer Research Foundation supported the work.