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New worm genome offers useful comparison
By ELI KINTISCH

Sequencing sheds light on other worm superstar

Mice are furry and eat cheese, while humans are hairy and slurp soy lattes.

C. elegans is a minuscule transparent worm specie of 959 cells found in soggy soil, while C. briggsae is, well, a minuscule transparent worm specie of about 1,000 cells found in soggy soil.

Which pair's genome do you think is more similar?

If you guessed the worms, your name is mud. Turns out that in terms of genomes, mice and humans are peas in a pod. But after 100 million years of divergent evolution, the virtually identical worms have genomes as different as manuals to a 2003 Acura and a 1977 Pinto Cruising Wagon.

"Genomically, you wouldn't predict that. You would think we wouldn't be more similar than the two worms," said computational biologist Lincoln Stein of Cold Spring Harbor Laboratory in New York. Stein is the first author of a new study describing the C. briggsae genome.

The reason is that while the worms' sequence may have been drastically revised over time, the genes that are important have stayed essentially the same.

The surprising finding is among the observations that a team of biologists at Washington University has made as it has sequenced the genome of C. briggsae.

The team, part of an international effort, is the first to sequence the worm's genome and has recorded a draft sequence of 98 percent of the worm's code. The results are being published in today's issue of Public Library of Science Biology.

While the work offers insights into the evolution of worms, mice and men, the main reason for the briggsae sequencing was to shed new light on superstar nematode C. elegans.

Since the sequencing of C. elegans' genome in 1998- an effort spearheaded by the Washington University's Genome Sequencing Center - genes found in the worm's code have led to clues on how human cells die, why we age and how cells process carbohydrates. This is one well-known worm: C. elegans' neurons have been completely mapped and the sequence of its genome is known to the letter.

But finding all the genes - think of them as sentences - among the 97 million letters has been tough, even with special gene-hunting computer programs. The C. briggsae code provides an emerging tool in the study of genomes: comparison.

Contrasting the two worm codes allowed the biologists, armed with new computer algorithms to find gold in the gibberish. Strings of letters in the code that are shared by the two species can be assumed to be important, said study co-author Michael Brent, a computer scientist at Washington University. They have survived hundreds of millions of years of evolution, so they're more likely to be genes or instructions telling the cell which genes to read when.

The comparative technique provided a powerful new proofreading method. For example, the researchers found evidence for 1,300 genes that had been missed in C. elegans.

"Only when you compare the two sequences does the light turn on," said the center's Richard Wilson, a project leader.

Comparing worm genomes "helps you to narrow your focus and decide which of the genes could provide for broad control of disease," said James McCarter, who worked with some of the authors on the paper when he did research at the Genome Sequencing Center. Now, as president of the St. Louis-based biotech firm Divergence, McCarter looks to use worm genomes to battle parasitic diseases like river blindness, which currently infects 18 million Africans.


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