The well-known laboratory animal Xenopus laevis, also known as the African clawed frog, has an exciting history.
This can be seen from its double genome. Nature will be publishing the study by American, Japanese and Radboud-based researchers on 20 October 2016. This makes the frog an interesting subject for gene evolution research.
Not so long ago in evolutionary terms, around seventeen million years ago, two species of clawed frogs encountered each other in the humid warmth of an African rainforest. Let’s call them Es (S) and El (L).
Es and El were distant cousins of each other; somewhere way back in time they had had a common ancestor. In any case, although they were not of the same species, there was some chemistry between them, and one thing led to another – several others in fact, in the form of many baby frogs, all with the complete sets chromosomes from both species. That’s what happens if two different species come together and produce descendants. In mammals, this results in infertile offspring; in yeasts, plants, fish and amphibians, however, the result can be the doubling of chromosomes which can in turn be passed on to the next generation. In this case, this resulted in a new species: Xenopus laevis, or the African clawed frog. Right up to the present day, this species has retained its double chromosome set: each individual now receives one L and one S from the father, and one L and one S from the mother, i.e. a total of four: tetraploid. Normally, a somatic cell is diploid, with two of each chromosome (one from the father and one from the mother).
Laboratory animal for a new research field
Millions of years later, Xenopus laevis became a highly-favoured laboratory animal for developmental biologists (the first pregnancy test!) and cell biologists, and this led to its double genome and the origins of the double genome being unravelled by American, Japanese and Radboud’s own researchers. The Nijmegen-based researchers contributed their specialisation to the project, namely their knowledge of epigenetics. This is the study of the ‘reading instructions’ for the DNA: epigenetic settings enable cells to specialise. The work of the Radboud researchers also includes the improvement of the gene annotation of Xenopus laevis – more is now known about which gene is found where on the genome.
According to Gert Jan Veenstra, Professor of Molecular Developmental Biology at Radboud University and one of the authors of the Nature study, the double genome makes this clawed frog an interesting subject for the research into genome evolution. Through comparison with a different Xenopus species without genome doubling (X. tropicalis), it is possible to reconstruct how the original genome must have looked. “The S and L chromosomes are not equally active. There seems to be a battle going on inside the cells.
The long L-chromosomes are doing better in that battle, while the already shorter S-chromosomes are gradually getting even smaller. You could say that the L-chromosomes are getting the better of the S-chromosomes. Gene degradation also takes place in cells with just one pair of chromosomes, but that is more likely to be fatal. In this frog, the breakdown of a gene on one chromosome is compensated by the same gene on the other. It therefore continues to live with broken or breaking genes.”
Dating by means of parasitic DNA
How do the researchers actually know that Xenopus laevis must have come into being seventeen million years ago through an encounter between two different species? Veenstra explains that this can be seen in features of the genome, such as the ‘parasitic DNA,’ small pieces of ‘foreign’ DNA (transposons) that integrate into the host DNA. “The DNA of those parasites is left behind on the chromosomes and then degenerates, and we can use this for dating purposes. Moreover, that parasitic DNA is the decisive evidence that Xenopus laevis developed from two separate species. The parasitic remnants on the S-chromosomes are different from those on the L-chromosomes. This is only possible if the S-chromosomes and the L-chromosomes existed separately from each other, i.e. in separate species.” Transposon parasites from later times are present on both the L-chromosomes and the S-chromosomes.
The interesting thing, as Veenstra explains, is that much further back in time – when vertebrates came into being – two genome doublings took place. Traces of this can be found in the DNA of humans. However, as these doublings took place so long ago, it is trickier to reconstruct exactly what happened. Xenopus laevis on the other hand is an ideal model for investigating genetic evolution by comparing it with X. tropicalis, its cousin with just one pair of chromosomes.
Not just fundamental
Genome doublings also occur in cancer cells. In Veenstra’s view, this is an additional reason to investigate these processes. “Now that we know about the genome doubling in Xenopus laevis, we can make informed choices about what we use this laboratory animal for. Xenopus laevis has a rich history in developmental biological research and cell biological research. Xenopus tropicalis is a more tractable model for genetic research; if you want to study gene evolution, however, X. laevis is a new model. Incidentally, there are also other frogs in the Xenopus family that are much more extreme, with eight or twelve sets of chromosomes. Who knows, we might also one day map out their genetic development history.”