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One adult and one juvenile of the leech Helobdella robusta.
One adult and one juvenile of the leech Helobdella robusta. The pair of black dots are eyespots or photosensors. These animals were being prepared for transport from the UC Berkeley to the Joint Genome Institute as part of a Community Sequencing Program. (Ajna S. Rivera) Image available for download

Lucky species queue up to have their genomes sequenced

– A tiny, nondescript green moss, a snail-killing leech and a fish parasite are among the lucky few species chosen to go to the head of the line of hundreds of thousands of Earth's creatures awaiting sequencing of their genome.

The moss, leech and parasite were among some two dozen organisms selected today (Tuesday, Aug. 24) by the Department of Energy's Joint Genome Institute (JGI) as the focus of their sequencing efforts over the next year.

The 23 projects - which include the moss genome project proposed by moss connoisseur and systematist Brent Mishler of the University of California, Berkeley; the leech genome project proposed by UC Berkeley developmental biologist David Weisblat; and the parasite project proposed by cell biologist W. Zacheus Cande - were chosen in part to provide researchers with genomes from a wide range of Earth's organisms, both plant and animal. But these organisms also are important economically or as disease pathogens, or are widely used research creatures in laboratories around the world.

Mishler called the moss genome project "a triumph for international plant science," complementing the handful of plant genomes known so far, including rice, corn, the mustard Arabidopsis and, soon to be complete, the poplar tree.

Other organisms chosen today for sequencing include an alga and the bacterium that causes Staph infections, plus a marine phytoplankton and two types of marine worms.

"The selections represent a rich diversity of microbes as well as higher plants and animals that inhabit both aquatic and terrestrial ecosystems," said Eddy Rubin, JGI director. "By making JGI's powerful resources available to non-traditional end-users of sequence through the Community Sequencing Program, we hope to advance knowledge across such vital topics as alternative energy production and bioremediation, and to address important questions of evolution and development."

Over the next year, JGI will devote nearly half its sequencing capacity to the projects, chosen from 60 proposals submitted earlier this year. JGI operates 100 DNA sequencers at its Walnut Creek, Calif., Production Genomics Facility, capable of sequencing more than 30 billion letters of genetic code (30 gigabases) each year.

 Leafy shoots, or gametophores, of the moss Physcomitrella patens.
Leafy shoots, or gametophores, of the moss Physcomitrella patens. This is a one-month-old colony of the laboratory strain of the moss. (David J. Cove/Leeds, UK)

The genome of the moss Physcomitrella patens, with only half a billion bases, is small compared to the human genome at 3 billion bases. But it could play a big role in plant studies, including patching together the evolutionary history of the tree of life.

"Physcomitrella is a wonderful model system in that it is small, grows quickly, and is very amenable to genetic and comparative studies," said Mishler, director of the University and Jepson Herbaria at UC Berkeley and a professor of integrative biology. "Human comparative genomics has benefited from having a series of genome projects along the tree of life - mouse, puffer fish, fruit fly, worm - while plant genomics has suffered, since only a closely related cluster of cereals and the mustard Arabidopsis have been sequenced. This will be a triumph for international plant science."

Mosses were among the first plants to colonize the land, 450 million years ago, predating the flowering plants by some 200 million years of evolutionary time.

"Mosses can still do many of the things that the flowering plants have forgotten," points out Mishler. "Some of their ancient traits - like the ability to survive extreme dehydration - would be useful to incorporate in modern-day crops. By studying the genes that control these traits in the moss, we should be able to identify how these characteristics might be revived in flowering plants."

A related plant also was chosen for sequencing by JGI - a Gemmiferous spike moss called Selaginella moellendorffii. Not a true moss, Misher said, Selaginella and the true moss Physcomitrella will be the first non-flowering vascular plants to be sequenced.

The leech Helobdella robusta, on the other hand, is a segmented worm (annelid) chosen for sequencing as a representative of the most mysterious of the three major groupings of organisms that, like humans, are bilaterally symmetric, that is, identical left to right. The leech genome will be among the first in the group Lophotrochozoa, which includes annelids and mollusks, plus a few other groups. Helobdella is a small freshwater leech that attacks pond snails, sucking them dry in a few hours.

Weisblat and Marty Shankland of the University of Texas at Austin, who proposed Helobdella for sequencing, have separately studied the leech embryo's early development for almost 30 years. Together with a small group of others, their labs have compiled a wealth of information that will come in handy when trying to identify the function of its genes. Though the leech is not as popular a lab animal as the nematode, C. elegans, or the fruit fly - both of which are members of the companion group Ecdysozoa - the leech is nevertheless important in understanding the origins of body segments.

  Spironucleus vortens
The microbe Spironucleus vortens uses its flagella to propel itself through the water. The one-celled creature, which is about 10 microns long, is one of the most ancient eukaryotes, dating from the time when eukaryotes branched off from the Earth's two other major lineages, the Bacteria and the Archaea.

"We hope the sequencing of the Helobdella genome will be a bootstrap for people interested in annelids in particular or the evolution of invertebrate body plans in general," Weisblat said.

In terms of human ancestors, the single-celled protist Spironucleus vortens holds a unique position - it is the earliest eukaryote, that is, a single-celled microbe that contains a nucleus. Though its cousin, the intestinal parasite Giardia, has already been sequenced, Cande says Spironucleus is a better representative of the basal eukaryotes because its genetics have not been altered by living as a parasite. Though Spironucleus lives in fish guts and has been implicated in hole-in-the-head disease in aquarium angel fish, it can live freely in water, Cande said.

"The genome of this very divergent organism, which has no energy producing mitochondria, doesn't engage in sexual reproduction and doesn't use oxygen, will help us understand the evolution of eukaryotic cells from the prokaryotes that have no nucleus," said Cande, a professor of molecular and cell biology and of plant and microbial biology.

Once the sequencing is complete, Mishler, Weisblat, Cande and their colleagues will end up, not with a complete list of the genes in each organism, but rather the raw sequences of DNA bases on each chromosome. The pinpointing and identification of genes within this sequence - a process called annotation - requires much more work on the part of researchers around the world. Arabidopsis, whose genome was sequenced in 2000, won't be completely annotated until 2010, Mishler noted.

"It's fun detective work," said Mishler of the annotation jamborees that draw many researchers together to look for genes among the raw sequence data. "But we're going to have to do a lot of work to annotate, including using classical genetics with crosses to map genes the old fashioned way, by looking to see if they're linked on the same chromosome or not."

The moss community gathered around the project, agreeing last year at a national meeting to recommend only this one moss for sequencing. Mishler and Ralph Quatrano of Washington University in St. Louis then proposed the project, with support from colleagues in England, Japan and Germany.

Since the Physcomitrella plants in culture are mostly from the British Isles, Mishler wanted to collect samples this fall of plants from California for comparative purposes. Old specimens in the herbarium collections came from the dried margins of local reservoirs, which is where Mishler and other UC bryologists are looking first. Just last week, the Jepson Herbarium's Dan Norris collected samples from San Pablo Reservoir.

The new collections will now be cultured and put in the pipeline for genetic analysis, and also used to help clarify the difficult species-level taxonomy, Mishler said, showing the synergism that can come from collaborations involving systematics and molecular biologists, natural history museums and genome centers.

"Physcomitrella doesn't do a lot - you can't eat it, it doesn't produce pharmaceuticals - but landmark genomes like this can help us make sense of the more complex genomes in higher plants," he said.

A complete list of organisms to be sequenced as part of JGI's Community Sequencing Program can be found at http://www.jgi.doe.gov/sequencing/cspseqplans.html.

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