November 9, 2006
Sea Urchin Genome Is a Biology Boon and a Computational Feat
Now that the entire DNA map of the sea urchin is complete, it’s clear that these spiny sea creatures are even closer genetic cousins to humans than suspected. Brown University professors Gary Wessel and Sorin Istrail helped reveal the secrets of the urchin – from its powerful immune system to its formidable gene regulatory network – by identifying individual genes and creating the first high-resolution map of genes activated in its embryo. The work appears on the cover of Science.
PROVIDENCE, R.I. — Scientists have long known that humans and sea urchins are closely related. In fact, these animals are the only invertebrates on the human branch of the evolutionary tree of life. Now that the sea urchin genome is sequenced and assembled, that genetic connection is even clearer.
After identifying 23,300 genes made from 814 million letters of DNA code taken from Strongylocentrotus purpuratus, the California purple urchin, an international science team has found that humans share 7,077 genes with urchins. This makes the spiny, spineless creature a closer genetic cousin to man than the fruit fly or worm, more widely studied model organisms. Results from the sequencing project are published in a special six-article section of Science.
Other surprises from the project: Urchins have the most sophisticated innate immune system of any animal studied to date. They carry genes associated with many human diseases, such as muscular dystrophy and Huntington’s disease. The urchin also has genes associated with taste and smell, hearing and balance.
And these eyeless animals can see – or at least sense light. How? Through their feet. Scientists found genes associated with vision, genes that are activated in the urchin’s tube feet, puny projections on the animal’s shells that help it move and feed. “Nobody would’ve predicted that sea urchins have such a robust gene set for visual perception,” said Gary Wessel, a Brown University biology professor and member of the Sea Urchin Genome Sequencing Consortium. “I’ve been looking at these organisms for 31 years – and now I know they were looking back at me.”
As part of the sequencing project, Wessel led the group of scientists who studied hundreds of thousands of letters of genetic code and identified the genes responsible for sea urchin reproduction. A professor in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown, Wessel runs one of the nation’s top sea urchin labs, using the animals to study fertilization and early development in humans.
With the ability to lay millions of eggs in a lifetime and with a clear embryo – one that allows scientists to identify and observe each individual cell at work – urchins are ideal organisms for understanding the burst of biological activity that occurs after sperm and egg merge. In just one month, a human embryo has produced thousands of cells that form all the major organs as well as the general body plan of head, torso and limbs. The urchin’s usefulness as a model system for developmental biology was a key reason for sequencing its genome. “We’ve already learned an enormous amount from the sea urchin, from something as basic as how identical twins form to in vitro fertilization procedures,” Wessel said. “With a complete map of the urchin’s DNA, we can now learn more quickly and easily how each process works during development.”
Sorin Istrail, a Brown professor of computer science and director of the University’s Center for Computational Molecular Biology, also served as a member of the sea urchin sequencing team. A former research director at Celera Genomics, the private company that sequenced the human genome, Istrail was one of eight scientists in the urchin project who pulled off a computational feat. The group identified every gene activated in the urchin embryo, publishing their results in a companion paper in Science.
This map, called a transcriptome, represents every experimentally authenticated messenger RNA molecule, or transcript, present in embryonic cells. This information tells scientists which genes are activated, or expressed, during the first two days of development. The group determined that at least 11,000 to 12,000 genes – or about half of all of the animal’s genes – are expressed in this critical early stage. “Understanding what genes are active in a cell at any given time is critical to biologists,” Istrail said. “This information can tell them what genes do and represents the first step in understanding how they work with other genes during development or aging, in health and during disease.”
While transcriptome maps have been created for other species, none has been completed so quickly. That’s because Istrail and the other scientists on the transcriptome team used a whole-genome tiling array custom-built by NASA. The array allowed them to insert 500,000 bits of DNA into 500,000 cells at a time to see which bits get copied into messenger RNA. The high-resolution transcriptome map helped scientists more rapidly identify and verify genes for the larger sequencing project.
“The sea urchin holds the key to the cis-regulatory code, the blueprint for gene regulatory systems and networks and the functional maps of the control circuitry of the cell,” Istrail said. “Now that we have the genome and transcriptome map, we can start to crack this code, which will reveal key insights into human genetics and evolution.”
The National Science Foundation and the National Institutes of Health supported Wessel’s work on the urchin genome. Brown University supported Istrail’s work on the project.