Researchers use frog for studying genome doubling

An international research consortium has reported a striking pattern of genome duplication in the African clawed frog Xenopus laevis, showing that the frog's genome arose through interspecific hybridizations of two now-extinct species between 15 and 20 million years ago.

Animals typically have paired sets of chromosomes, with one set inherited from mom and the other from dad. African clawed frogs, however, have twice as much deoxyribonucleic acid (DNA) as other frogs, and four sets of chromosomes, a condition known as tetraploidy, which is common in plants and some amphibians, reptiles and fish, but rare in other animals.

By sequencing and analyzing the African clawed frog genome, the researchers found that its four sets of chromosomes were organized as two paired sets, one "long" and the other "short." Each parent contributes one long and one short set to its offspring. Confirming a longstanding hypothesis, the analysis shows that the long and short sub-genomes of X. laevis were originally derived from two conventional frog species.

The genome sequence of the most common laboratory frog, as reported this week in the journal Nature, reveals that through a process of interspecies mating, these two progenitors merged to form a new species that eventually became today's African clawed frog.

Once brought together, the two conventional sub-genomes combined to form a "supergenome" with extra copies of every gene. The two sub-genomes needed to collaborate to guide the functions of the new species, and deal with any conflict between them. The researchers found that the two progenitor genomes responded differently to the merger. While one remained more or less intact, the other shrunk by large- and small-scale deletion and disruption of its genetic material, resulting in the "long" and "short" sub-genomes we see today.

The frog genome provides insights into the behavior of anciently duplicated genomes. Several thousand genes have become disabled since the hybridization, and the international team led by researchers with the University of California, Berkeley, and the University of Tokyo found nearly a thousand non-functional "dead" genes, others dying, and still others that had been completely lost.

Similar events are thought to have occurred nearly half a billion years ago in the evolutionary lineage leading to modern vertebrates, according to a news release from UC Berkeley, and the frog provides a contemporary laboratory for studying the impact of genome doubling.

African clawed frogs of the genus Xenopus comprise more than 20 species native to sub-Saharan Africa. In the early 20th century, biologists discovered that female frogs respond to human hormones, and that injecting frogs with a woman's urine could be used for a simple pregnancy test. The frogs became a standard diagnostic tool, and commonplace in hospitals and research laboratories.

Researchers soon realized that Xenopus was also a valuable and versatile laboratory model for basic biology, enabling studies that shed light on both fundamental mechanisms of vertebrate embryonic development and mechanisms underlying human diseases. "Because X. laevis is such a well-studied model system for cell and developmental biology, it is ideal for exploring the effect of polyploidy on genome evolution," said Richard Harland, a professor of molecular and cell biology at UC Berkeley.

Since the 1970s it has been known that many Xenopus species have two, four or even six times as much DNA as most other frogs, along with comparable multiplications of the fundamental chromosome set.

Although both of the progenitor species are now extinct, the research team identified telltale genomic signals that two species were involved, and inferred that they came together 15-20 million years ago to form the species we now know as Xenopus laevis. "It's as if the genome we see today was written long ago by two different authors, who each had their own favorite words that they used over and over again," said Daniel Rokhsar of UC Berkeley.

The Xenopus laevis genome encodes a frog whose cells and body size are larger than those with smaller genomes. In the millions of years since the merger, there have been subtle, and not-so-subtle, changes in the genome as it adjusted to its new circumstances. In addition to gene loss, the timing of activity during embryonic development has been tweaked for thousands of genes.

"We have only scratched the surface in analyzing the Xenopus laevis genome," said Masanori Taira, a professor of biological sciences at the University of Tokyo. "It is a treasure trove of information for biologists interested in the evolution of genomes and the control of cell and body size." Endit