Frogs and humans are kissing cousins
Gene order of shows surprising similarity to that of mammals.
What's the difference between a frog, a chicken, a mouse and a human? Not as much as you'd think, according to an analysis of the first sequenced amphibian genome.
The genome of the western clawed frog, Xenopus tropicalis, has now been analysed by an international consortium of scientists from 24 institutions, and joins a list of sequenced model organisms including the mouse, zebrafish, nematode and fruit fly. What's most surprising, researchers say, is how closely the amphibian's genome resembles that of the mouse and the human, with large swathes of frog DNA on several chromosomes having genes arranged in the same order as in these mammals. The results of the analysis are published in Science this week1.
"There are megabases of sequence where gene order has changed very little since the last common ancestor" of amphibians, birds and mammals about 360 million years ago, says bioinformaticist Uffe Hellsten at the US Department of Energy's Joint Genome Institute in Walnut Creek, California, a co-author on the study.
That close genomic relationship doesn't hold true for all vertebrates, he notes. The zebrafish genome, for example, shows a much different gene order.
Such conservation has important evolutionary implications. "By comparing the genomes of these different animals, you can really tell what the ancestral complement of genes may have been," says Richard Harland, a molecular and developmental biologist at the University of California, Berkeley, who also took part in the study.
In addition, says Harland, it belies the view that genomes as a rule evolve quickly. "I think the old expectation was that there was a lot of chromosome rearrangement, but I think increasingly we are finding that chromosomal translocations are pretty rare."
The similarity in genome sequence also validates the frog as a human disease model. Within conserved sequences in X. tropicalis, the researchers found genes that are similar to 80% of human genes known to be associated with diseases. "It's going to make genetic screens in Xenopus immediately more useful," says Frank Conlon, a geneticist at the University of North Carolina in Chapel Hill, who is not an author of the new study but helped to assign biological functions to genes in the sequence.
Having the sequence in hand, he adds, provides a crucial tool for bringing a host of Xenopus assays on basic biological functions — such as cell division, protein expression and phenotype identification — down to the genomic level.
Prince among frogs
X. tropicalis has gained a foothold as a model organism in the past decade, but it isn't the most widely studied frog species. Since the 1940s, its cousin the African clawed frog, Xenopus laevis, has been the go-to organism for developmental and cell biologists. Both species are easy to raise, having large eggs and transparent tadpoles that are especially conducive to studies of development and embryology.
X. tropicalis, however, is smaller in size and matures in four months rather than two years — making it a more tractable choice for studies that relate phenotypes to specific genetic mutations. In addition, because it has a diploid genome — two copies of each gene — the X. tropicalis genome is easier to sequence and compare to other species than X. laevis, in which most of the genes are present in four copies (tetraploid) rather than the usual two. Although the first draft of the X. tropicalis sequence was released in 2005, this is the first published analysis of the genome1.
The Xenopus sequencing project began in 2002, before the advent of next-generation sequencing, and researchers chose to sequence X. tropicalis because at the time "it was hugely daunting to think about the X. laevis genome," says John Wallingford, a developmental biologist at the University of Texas at Austin. But that's starting to change. Wallingford's lab has begun sequencing X. laevis, and Harland's lab has plans to do the same.
Comparing the diploid and tetraploid sequences of the two species will bring insight into how and why genes get duplicated, and what such changes mean for an organism, says Conlon. "I know of no other vertebrates where you can study genome duplication," he adds. "I think it's a really unique opportunity for evolutionary biologists."
- Hellsten, U. et al. Science 328, 633-636 (2010).