A prickly subject: The sea urchin genome is sequenced

BAR HARBOR, MAINE -- Nov. 9, 2006 Who would have guessed that the lowly sea urchin, that brain-less, limb-less porcupine of the sea, would be the star of a multi-million dollar, worldwide effort to map out every letter of its genetic code? Or that the information gathered in that effort may eventually lead to new treatments for cancer, infertility, blindness, and diseases like muscular dystrophy and Huntington's Disease?

James Coffman, Ph.D., of the Mount Desert Island Biological Laboratory in Bar Harbor was one of the scientists who helped decode the 814 million pairs of nucleotide bases in the sea urchin's chromosomes. The Human Genome Sequencing Center at Baylor College of Medicine in Texas led the project and announced the completion of the three-year project today. Having the complete genome, Coffman says, "makes doing research on urchins so much easier."

Why would anyone want to do biomedical research on sea urchins? According to Coffman, sea urchins are remarkably similar to humans in many ways, sharing most of the same gene families, and yet differ in a few critical areas besides the obvious physical ones. For one thing, sea urchins have a "extraordinarily complex innate immune system" which is not based on antibodies, like that of jawed vertebrates, but is effective enough to give sea urchins a surprisingly long life span of up to a hundred years or more.

Innate immunity refers to a set of proteins that are "hard wired" to detect unique aspects of bacteria and signal to an organism's cells that there is an intruder. The rich repertoire of such proteins in sea urchins could end up providing new tools for use against infectious diseases.

Sea urchins are also extremely good at dealing with potential chemical threats in their environment through a "defensome" a group of genes which can sense and then transform and eliminate threats from potentially toxic chemicals. Without this sophisticated response, these chemicals, including heavy metals, can lead to aging, illness and death, so it would be valuable to learn how sea urchins defend themselves against them.

In terms of evolution, sea urchins are in an interesting position between vertebrates and invertebrates. "The sea urchin fills a large evolutionary gap in sequenced genomes," said George Weinstock, Ph.D., co-director of the sea urchin sequencing project. Being more closely related to humans than other invertebrates such as flies and worms, "it allows us to see what went on in evolution after the split between the ancestors that gave rise to humans and insects. The sea urchin genome provided plenty of unexpected rewards and was a great choice for sequencing."

In the 1990s, sea urchins became a valuable fishery in Maine, but their stocks were quickly depleted. Linda Mercer, Director of the Bureau of Resource Management at Maine's Department of Marine Research, welcomed the news of the project's completion: "We are certainly interested in reestablishing the sea urchin population along the Maine coast, and any research that can continue to improve our understanding of sea urchin biology would be helpful."

The DNA that was sequenced came from a male California purple sea urchin, not one of the green sea urchins that live in Maine waters. Purple urchins are found along the west coast from Baja to Alaska, whereas the green ones, close relatives of the purple, are found in cold Northern waters on both the east and west coasts.

All sea urchins, however, have round shells covered with spines. Like the other members of the phylum Echinodermata, which includes starfish and sea cucumbers, they have fivefold symmetry and move by means of hundreds of tiny, adhesive "tube feet." They eat algae with a mouth surrounded by five teeth on the bottom of their shell and excrete through a hole at the top.

The sea urchin has long had a strong fan base among scientists. One reason it was chosen for the genome-sequencing project is the size of the sea urchin research community. Over 140 laboratories are using sea urchins as a primary research organism. Annotation of the sequenced genome was conducted by 240 scientists in 11 countries.

In fact, it was research conducted on sea urchins over a hundred years ago that led to one of the breakthroughs of modern biology, when Theodor Boveri discovered in 1902 that normal development requires that every cell in an embryo have a full set of chromosomes carrying the genetic or inherited material for an organism.

One reason sea urchins have been so popular with scientists is that they are easy to work with. They can live in a laboratory comfortably, release their eggs readily, and have transparent embryos. That makes it easy to observe their fertilization and development, which is surprisingly similar to human embryonic development in some ways. As Dr. Coffman says, "Studying gene function and regulation in early sea urchin embryos is relatively easy compared with other model organisms such as mice, and much faster."

Sea urchins are also incredibly fecund. A single female discharges millions of eggs. In fact, most of an urchin's body mass consists of its reproductive organs, and that's what people are consuming when they eat the "roe" from a sea urchin.

At first glance, sea urchins seem to be inanimate, although people who have been around sea urchins know that the spines will move quickly in reaction to a light touch. The genome project, however, revealed that urchins have genes encoding some of the same sensory proteins involved in vision and hearing in humans. Yet the sea urchin has no eyes and ears, at least as we know them. Some of the visual sensory proteins are localized to an appendage known as the tube foot, and probably function in sensory processes there.

"The sea urchin reminds us of the underlying unity of all life on earth," notes Erica Sodergren, Ph.D., co-leader of the sequencing project. At MDIBL, Dr. Coffman is hoping to exploit that unity to ultimately find new treatments for human diseases and is studying a sea urchin member of one of those shared families of genes known as the "Runx" genes. In vertebrates this family of genes is known to be important for developmental processes such as bone and blood formation, and its mutations are associated with bone disorders and a common form of childhood leukemia.

Now that the sea urchin's genome has been sequenced, Dr. Coffman's work should progress more quickly. "It's incredible," he says. "It's hard for me to imagine not having a genome now."

The Mount Desert Island Biological Laboratory, founded in 1898, is one of the leading marine research institutions in the world. The nonprofit, independent research institution has a three-fold mission: to promote research and education in the biology of marine organisms; to foster understanding and preservation of the environment; and to advance human health.

Also here:

http://www.biologynews.net/archives/2006/11/09/sea_urchin_genome_is_a_biology_boon_and_a_computational_feat.html

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."

Source : Brown University

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