First Frog Genome Sequenced

Researchers published a draft genome of the western clawed frog Xenopus tropicalis—the first amphibian genome to be sequenced. The accomplishment will not only yield insights into evolution; it could also lead to a better understanding of many human diseases.

Scientists chose X. tropicalis for initial sequencing over the related African clawed frog Xenopus laevis, which has been used extensively in scientific laboratories. Studies of X. laevis have helped answer basic questions about body development, including how organs form and how cell fates are decided. However, X. laevis poses difficulties for genetic studies. It takes 1 to 2 years to mature, and its genome is nearly twice as large as that of X. tropicalis due to an ancient duplication of its chromosomes.

X. tropicalis is an ideal substitute because it has only 2 copies of each chromosome, matures in only 4 months, and requires less space to house than the larger X. laevis. A team of scientists led by the U.S. Department of Energy (DOE) Joint Genome Institute and the University of California, Berkeley, set out to add to the set of X. tropicalis research tools by sequencing its genome. The team, which included researchers from NIH’s National Library of Medicine (NLM) and National Cancer Institute (NCI), was supported by DOE, along with NIH’s National Human Genome Research Institute (NHGRI) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The team reported in Science on April 30, 2010, that the X. tropicalis genome encodes more than 20,000 protein-coding genes. At least 1,700 of these are related to human disease genes, accounting for about 80% of all the known human disease genes.

The researchers also found that genes on long stretches of the X. tropicalis genome are often arranged similarly to the equivalent genes on human and chicken chromosomes.

"When you look at segments of the Xenopus genome, you literally are looking at structures that are 360 million years old and were part of the genome of the last common ancestor of all birds, frogs, dinosaurs and mammals that ever roamed the earth," explains first author Dr. Uffe Hellsten of the DOE's Joint Genome Institute. "Chromosome archaeology helps us to understand the history of evolution, showing us how the genetic material has rearranged itself to create the present day mammalian genome and present day amphibian genome."

"A lot of furry animals have been sequenced, but far fewer other vertebrates,"says co-author Dr. Richard Harland of UC Berkeley. "Having a complete catalog of the genes in Xenopus, along with those of humans, rats, mice and chickens, will help us reassemble the full complement of ancestral vertebrate genes."

—by Harrison Wein, Ph.D.