Carnegie Mellon scientist plays key role in unveiling sea urchin genome

PITTSBURGH--Carnegie Mellon University has played a key role in an international, multi-institutional collaboration to sequence the sea urchin genome. Sea urchins, close relatives of vertebrates, have been studied extensively for more than 150 years as a model system of embryonic development. Now, a summary of the sea urchin genome, published Nov. 10 in the journal Science, should make these creatures even more useful for future research into various aspects of development, immunity, nerve cell communication and evolutionary relationships with humans and other vertebrates.

"Having the complete sequence of the sea urchin genome will make a powerful model system stronger still. Given the full catalogue of genes, methods for manipulating their expression and the many other experimental virtues of sea urchins, the possibilities are almost limitless now in terms of what we can do to study mechanisms of embryonic development using this system," said Charles Ettensohn, biological sciences professor at Carnegie Mellon and one of the principal investigators who helped establish the project. He also led the team that cataloged the genes responsible for building the sea urchin's embryonic skeleton.

The Sea Urchin Genome Sequencing Consortium sequenced and analyzed the genetic code of Strongylocentrotus purpuratus, the California purple sea urchin, which is roughly one-fourth the size of the human genome. Because sea urchins are the closest known relatives of the chordates (the phylum that includes humans), analyzing the sea urchin genome is significant as scientists can now compare the genomes of organisms from divergent evolutionary branches of the tree of life. By comparing sea urchin genes to human genes, scientists can better understand -- at the level of the genetic sequence -- what makes humans (and other chordates) unique. According to Ettensohn, scientists can also determine how much of the human and sea urchin "genetic toolkit" was already present in their last common ancestor and, conversely, what genes have appeared more recently in the two lineages since they diverged many hundreds of million years ago.

"Having the sea urchin genome is almost an epiphany. I can see the genes, and it's very exciting," added Ettensohn, who has been studying the sea urchin as a model of development for more than 25 years. Specifically, he focuses on the vast network of proteins needed for these animals to form skeletons through biomineralization.

"If we understand how sea urchins build their skeletons, we can learn more about how we build our skeletons," Ettensohn said. "Additionally, understanding how natural systems build skeletons can help us mimic that in the design of materials to treat bone disease and injury in humans."

As part of the Sea Urchin Genome Sequencing Consortium, Ettensohn contributed 51,000 cDNAs -- about one-third of the total genomic material critical for the assembly of the genome and for the accurate prediction of where genes lie within the DNA sequence.

The Ettensohn lab was also one of 15 labs to annotate sets of genes that comprise the sea urchin genome. Initially, computers assembled the genome sequence and predicted the sea urchin genes. These predictions were then verified by scientists in the lab. Ettensohn annotated the genes involved in biomineralization, the process by which sea urchins form their embryonic skeletons. His work resulted in a comprehensive catalog of all the genes that are actually being used by the embryonic cells responsible for building the skeleton, including when and where the genes are expressed in the embryo.

In the sea urchin embryo, specialized cells produce proteins that mix with mineral crystals, thereby regulating the growth and shape of the emerging skeleton, just as in humans. But having the sea urchin genome has revealed a provocative discovery: many of the biomineralization proteins, especially those that control late stages of the process, are completely different in sea urchins and humans. According to Ettensohn, the challenge now is to uncover the basic principles that allow sea urchins and humans to build biomineralized structures using these different "building blocks."

Having the sea urchin genome enhances this effort. Ettensohn and others are "knocking out" biomineralization genes to prevent them from making the proteins that comprise the skeleton. Because the embryonic phase of development takes place in only two days, and because the embryo is beautifully clear, researchers can actually watch this amazing embryonic skeleton form. Specifically, they can look at the embryonic skeleton to see how it has been perturbed by certain genetic knockouts. Ultimately, this work could enable researchers to piece together the intricate process by which the sea urchin skeleton is formed.

According to the report in Science, researchers also found that the sea urchin has genes similar to vertebrate genes associated with vision, hearing, balance and other sensory tasks, and yet these primitive animals do not have organized sensory structures that look like ears or eyes. Further investigation of these characteristics may uncover new concepts of perception, Ettensohn said.

The sea urchin genome also includes genes associated with a diverse and sophisticated immune system. Studying the molecular mechanisms by which sea urchins protect themselves against bacteria and viruses may unlock new methods for preventing disease in humans, the authors report.

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The National Human Genome Research Institute of the National Institutes of Health provided most of the funding for the Sea Urchin Genome Sequencing Project.

For more information, visit www.bio.cmu.edu/labs/EttensohnWebPage/home.html, www.hgsc.bcm.tmc.edu/projects/seaurchin/ or http://sugp.caltech.edu/.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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