Sea-Urchin Genome Sequenced

A group of 240 researchers from an international consortium of more than 70 institutions has announced the sequencing of the male California purple sea urchin. The project was led by Erica Sodergren and George Weinstock, a husband-and-wife team at the Baylor College of Medicine-Human Genome Sequencing Center (BCM-HGSC), along with Richard Gibbs, director of the BCM-HGSC, and Caltech’s Eric Davidson, the Chandler Professor of Cell Biology, and Andrew Cameron, a senior research associate in biology. The purple sea urchin’s genome has been studied intensely for years at Caltech, and the organism is a workhorse of developmental and biomedical research. Davidson and Cameron coordinated the sequencing effort, and Caltech’s Kerckhoff Marine Laboratory provided all the sea urchins required for the project.

Reported in the November 10 issue of Science, the high-quality “draft” sequence covers more than 90 percent of the sea-urchin genome. The genome contains more than 814 million letters, spelling out 23,300 genes, nearly 10,000 of which have already been scrutinized by the consortium. In addition to the primary results in Science, 41 companion manuscripts will appear in Science and in a special December 1 issue of Developmental Biology.

More than 30 years ago, Davidson and Roy Britten, a distingushed senior research associate at the marine lab, began to use the sea urchin as an experimental animal and decided to develop it as a model system in the then-emerging field of molecular biology. As a result, “Britten and Davidson offered a comprehensive theory of gene regulation in higher organisms, and the sea urchin has been the premier model for testing these predictions,” says Gibbs. “The complete sequence is now available to further these studies.”

Sea urchins are echinoderms—Greek for spiny skin—a phylum of marine animals that originated over 540 million years ago and includes starfish, brittle stars, sea lilies, and sea cucumbers. The purple sea urchin is a recent arrival, however, emerging in the North Pacific some 15–20 million years ago. Sea urchins and humans share a common ancestor that gave rise to the deuterostomes, the superphylum that includes the echinoderms and the chordates, essentially animals with a spinal cord.

The sea urchin is the first nonchordate deuterostome to be sequenced. (Insects, nematodes, and other such creatures that have been sequenced lie outside the deuterostome superphylum.) “Each genome that we sequence brings new surprises. This analysis shows that sea urchins share substantially more genes and biological pathways with humans than previously suspected,” says Francis S. Collins, director of the National Human Genome Research Institute. “The sea urchin fills a large evolutionary gap in sequenced genomes,” says Weinstock, codirector of Baylor’s Human Genome Sequencing Center, which did the sequencing work. “It allows us to see what went on after the ancestral split that gave rise to humans and insects.”

Comparing the sea-urchin to the human gene list shows which human genes are likely to be recent innovations. It also shows which human genes are evolving rapidly in response to natural selection. This will make it possible one day to know the history of every human gene—and build a picture of what the extinct ancestors that gave rise to animals ranging from worms to humans looked like.

Sea urchins sure don’t look like people, but our embryonic development displays many basic similarities, an important shared property of deuterostomes. This makes the sea urchin, with its many transparent embryos and easily isolated eggs and sperm, a valuable model organism. Animal development occurs through a complex network of genes, and sea urchins provide a rapid and efficient means of manipulating that network, allowing researchers to figure out which genes turn other genes on and off. Consequently, the sea urchin is among the best understood developmental systems among animal models. Now, with the genome sequence in hand, this process can be studied exhaustively.

Because of its evolutionary position, the sea-urchin genome is a sample of unknown biological territory, the early exploration of which is already bearing fruit. The sea urchin has most of the same gene families as people, but the gene families are often larger in humans. One unexpected exception to this rule is the immune system. Humans have innate and acquired immune systems. Innate immunity is the set of proteins that are “hard wired” to detect unique molecules within bacteria, such as their cell walls, and to signal that there is an intruder. Acquired immunity is the province of cells that “learn” to recognize specific invaders and then create customized antibodies to fight them. The sea urchin has some acquired immune system genes, but its innate immune branch is greatly expanded—10 to 20 times as many genes as in humans. This rich repertoire of sea urchin proteins could turn out to provide new reagents in the fight against infectious diseases.

And the sea urchin has no eyes and ears, at least as we know them, yet it has genes for sensory proteins that are involved in human vision and hearing. Some of the visual sensory proteins are localized within an appendage known as the tube foot, and likely function in sensory processes there. “The sea urchin reminds us of the underlying unity of all life on earth,” notes Baylor’s Erica Sodergren. “It is a similar set of genes and proteins being reused in different ways, in different numbers, and at different times in the life cycle to create the diversity of living forms.”

The National Human Genome Research Institute of the National Institutes of Health provided most of the funding for the sequencing and annotation. —RT