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.