Carnegie Mellon scientist helps to crack purple sea urchin genome

Michael M. Whiston Nov 20, 2006

When it comes to genetics, looks can be deceiving. On the surface, sea urchins appear to share little in common with humans, but on the inside, these organisms could provide insight into the beginnings of human growth.

In fact, thanks to Carnegie Mellon biology professor Charles Ettensohn, you may never look at sea urchins the same way again.

Ettensohn worked alongside 200 researchers worldwide to discover the genome of the California purple sea urchin. He provided researchers with 51,000 complementary DNAs (cDNAs), or about one-third of the genomic information necessary to sequence the genome.

cDNA is so called because its sequence of bases is the complement of a given DNA sequence. By finding the DNA sequence’s complement, scientists can find the sequence of the actual DNA. In that sense, scientists can work backwards to figure out entire DNA sequences.

Sea urchins are relatives of chordates, the phylum to which humans belong, making sea urchins useful for studying the embryonic development of humans.

The Sea Urchin Genome Sequencing Consortium is a team of researchers based out of the Human Genome Sequencing Center at Baylor College in Houston, Texas. The center was responsible for sequencing the genome.

The sea urchin genome is very long, said Ettensohn, but most of the genome remains unexpressed because it is inactive. In contrast, cDNAs are parts of an organism’s genome that are expressed.

“The cDNAs let you get an idea of what part of the genome is active,” he said.

Ettensohn’s lab used cDNAs to verify computer predictions of gene locations along the sea urchin genome. In particular, computers looked for sequences within the sea urchin genome that were similar to sequences in other organisms.

Ettensohn said that sea urchins have been used for over a century and a half as a model system for studying embryonic development, partly because of their external fertilization system.

“The fact that [fertilization] happens outside the mother means that you can study the process very easily,” he said.

The embryos are also easy to see, “like glass,” said Ettensohn.

Ettensohn’s lab sequenced the part of the sea urchin genome responsible for building the sea urchin’s skeleton. Ettensohn is studying the influence of individual genes on embryonic development by turning certain genes on and off.

“The goal is basically to understand how genes control development,” said Ettensohn.

But researchers had to begin small before looking at individual genes.

The entire genome contains around 23,000 genes. Researchers began their study by breaking the genome into pieces, using computers to search for patterns and overlaps in the genetic material.

These patterns allowed researchers to assemble the gene.

Greg Wray, a professor of biology at Duke University, said, “The first part is really a jigsaw puzzle issue.”

After the individual parts of the genome are strung together, the genome is annotated, or interpreted, based on comparisons with other organisms.

If researchers know the function of similar genes in other organisms, then they can deduce the function of sea urchin genes.

“We’re trying to find features that mean something in what is otherwise just alphabetical soup,” Wray said.

Researchers are now trying to discover genetic similarities among sea urchins and humans that could account for embryonic development.

By modifying a sea urchin gene, researchers can learn more about the regulatory process and proteins that underlie early growth.

Wray said that this is his favorite stage of the project.

“Everything up to then is operational — you have to do it to get to the fun part.”

Also, the use of sea urchins is cheap. Whereas a mouse experiment costs around $20,000, said Wray, a sea urchin experiment costs only $100.

The downside of using sea urchins, however, is that, in evolutionary terms, they are further from humans than mice.

Wray said that while sea urchins are a starting point for understanding human genes, mice allow for more detailed analysis.

“You can think of it as a screening process,” he said.

Andrew Cameron, a senior research associate at the California Institute of Technology, also provided researchers with collections of cDNA. The collections were taken from expressed RNAs in the sea urchin.

According to Cameron, appearances can be deceiving.

“Here we have an animal that looks very different than us, yet it has a much more similar genome to us then a fly or a worm does.”

Now that the genome has been sequenced, Cameron said, researchers will be able to study genes more efficiently. In particular, researchers can now focus on identifying specific regions within the genome.

For instance, the sea urchin genome contains regulatory regions that control gene expression. Researchers can discover these regions by comparing the sea urchin genomes to similar species.

“People can find ways to study genes many ways at once,” Cameron said.

The genomic sequence can be viewed on the Human Genome Sequencing Center Sea Urchin website at www.hgsc.bcm.tmc.edu/projects/seaurchin.