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PUBLIC RELEASE DATE:
9-Nov-2006

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Contact: Ross Tomlin
htomlin@bcm.edu
713-798-4710
Baylor College of Medicine
@bcmhouston

Decoded sea urchin genome shows surprising relationship to man

Discoveries include novel immune system, unexpected sensory proteins and broad similarity to human genes

The Sea Urchin Genome Sequencing Project (SUGSP) Consortium, led by the Human Genome Sequencing Center at Baylor College of Medicine (BCM-HGSC) in Houston, announced today the decoding and analysis of the genome sequence of the sea urchin, Strongylocentrotus purpuratus.

The genome of a male California purple sea urchin was sequenced, and it contained over 814 million letters, spelling out 23,300 genes. Nearly 10,000 of the genes were scrutinized by an international consortium of 240 scientists from over 70 institutions in 11 countries. The high quality "draft" sequence covers over 90 percent of the genome. The primary results are presented in the Nov. 10 issue of Science, and 41 companion manuscripts describing further detailed analyses are contained in Science and a special issue of Developmental Biology appearing on Dec. 1.

The BCM-HGSC generated the sequence data for the SUGSP, then assembled the genome and led the analysis consortium. Additional resources for the project included a BAC library (clones with very large pieces of DNA) prepared at the California Institute of Technology and a physical map prepared at the Michael Smith Genome Sciences Centre at the British Columbia Cancer Agency in Vancouver.

The project was led by Drs. Erica Sodergren and George Weinstock, a husband and wife team at the BCM-HGSC, along with Dr. Richard Gibbs, director of the BCM-HGSC, and Drs. Eric Davidson and Andrew Cameron of the California Institute of Technology. The National Human Genome Research Institute of the National Institutes of Health provided most of the funding for the SUGSP.

Sea urchins are echinoderms (Greek for spiny skin), marine animals that originated over 540 million years ago and include starfish, brittle stars, sea lilies, and sea cucumbers. Following the great extinction of animals 250 million years ago, the modern sea urchins emerged as dominant echinoderm species. The purple sea urchin emerged in the North Pacific Ocean during a rapid burst of speciation and diversification 15-20 million years ago.

There was great interest in the sea urchin as a target for genome sequencing because these animals share a common ancestor with humans. That ancestor lived over 540 million years ago and gave rise to the Deuterostomes, the superphylum of animals that includes phyla such as echinoderms and chordates, the phylum to which humans and other vertebrates belong. All Deuterostomes are more closely related to each other than they are to any other animals not included in the Deuterostome superphylum. For example, among sequenced genomes, the genomes of fruit flies and worms are more distant from the sea urchin genome than is the human genome.

"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," said Dr. Francis S. Collins, director of the National Human Genome Research Institute at the National Institutes of Health. "Comparing the genome of the sea urchin with that of the human and other model organisms will provide scientists with novel insights into the structure and function of our own genome, deepening our understanding of the human body in health and disease."

To discover how sea urchins and humans can be so different yet be related by descent from an ancient relative, their genomes were compared. The sea urchin is an invertebrate and the first example of a Deuterostome genome outside the chordates. Most previous invertebrate genomes that were sequenced, such as insects and nematodes, were animals outside the Deuterostome superphylum, although one genome of a chordate invertebrate, the sea squirt, has been sequenced. The sea urchin lies evolutionarily in a large niche between the chordate branch of the Deuterostomes and the non-Deuterostome superphyla.

"The sea urchin fills a large evolutionary gap in sequenced genomes," said Dr. George Weinstock, co-director of the BCM-HGSC. "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."

The comparison of the genes of the sea urchin to the human gene list shows which human genes are likely to be recent innovations in human evolution and which are ancient. It also shows which human genes have changed slowly in the lineage from the ancestral Deuterostome animal and which 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 animal life from worms to humans looked like.

Although invertebrate sea urchins have a radically different morphology from humans and other vertebrates, their embryonic development displays basic similarities, an important shared property of Deuterostome animals. This distinguishes them from Protostomes, which have a different pattern of embryonic development.

This makes the sea urchin, with its many useful properties such as ease of isolation of eggs and sperm and transparent embryos, a valuable model to study the process of development and help understand human development. The development of the animal occurs through a complex network of genes, and the sea urchin is one of the main models for systems biology, the description of how the building blocks of an animal interact in time and space.

Sea urchins provide a rapid and efficient gene transfer system. By injecting DNA into the egg, researchers can determine which letters spell instructions for turning genes on and off. The series of genetic switches leading to the ordered cascade of expression of genes after fertilization in the sea urchin is among the best understood developmental systems among animal models. Now, with the genome sequence in hand, a more complete set of components of development are known and this process can be studied exhaustively.

"More than 30 years ago Roy Britten and Eric Davidson offered a comprehensive theory of gene regulation in higher organisms, and the sea urchin has been the premier model for testing these predictions," said Gibbs. "The complete sequence is now available to further these studies."

Because of its evolutionary position, the sea urchin genome sequence was a sample of unknown biological territory. Some of the notable discoveries were:

1.) The sea urchin had most of the same gene families found in man, the Deuterostome toolkit used to create animals in this superphylum. However, the size of gene families was often larger in humans, reflecting in part two whole genome duplication events during vertebrate evolution, after the separation of the sea urchin and human evolutionary lines.

2.) One unexpected exception to this size rule was the immune system. Humans have innate and acquired immunity systems. The sea urchin has some of the genes of the acquired immunity system, but its innate immunity branch is greatly expanded with 10 to 20 times as many genes as in humans.

Innate immunity is the set of proteins that are "hard wired" to detect unique molecules of bacteria, such as their cell wall, and signal that there is an intruder. This rich repertoire of sea urchin proteins could turn out to provide new reagents in the fight against infectious diseases.

3.) The sea urchin has genes for sensory proteins that are involved in vision and hearing in man. 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 likely function in sensory processes there. It is remarkable that the same sensory proteins are used in organs with such different structures in sea urchins and man.

"The sea urchin reminds us of the underlying unity of all life on earth," notes Sodergren, co-leader of the project. "It is a similar set of genes and proteins being reused in different ways, different numbers, and at different times in the life cycle to create the diversity of living forms."

The sea urchin genome was one of the most challenging to sequence to date at the BCM-HGSC. The genome was highly polymorphic, meaning that the two copies of the genome in the diploid organism varied from each other by about four percent, or one difference in spelling every 25 letters. This posed a formidable challenge in assembling the nine million separate short sequences produced by DNA sequencing.

A new approach was used, emphasizing the use of BAC clones as a framework. Each BAC clone represents only one version of the genome spelling and thus provides a consistent sequence on which to build the genome. To sequence the 8,000 BAC clones covering the genome, another new technique was used. The process, CAPSS (clone-array pooled shotgun sequencing), sequences mixtures of BAC clones, rather than individual ones, and then assigns portions of the mixture of sequences to the proper clone. This reduces cost and time to do the genome by an order of magnitude. The SUGSP was thus a test bed for innovations in whole genome sequencing.

The sea urchin project is one of more than 20 animal genomes the BCM-HGSC has undertaken, including human and primates like rhesus monkey, other mammals like the cow and wallaby, insects such as honey bee, beetle, and wasp, and most recently the dolphin. In addition, numerous microbes have been sequenced, with a focus on infectious diseases. Other projects at the BCM-HGSC are studying the genetic basis of human disease, which will be the major emphasis of future work.

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