An international team of scientists including the University of Calgary’s Peter Vize, Kamran Karimi and Vaneet Lotay has unlocked the DNA secrets of Xenopus laevis, a frog unlike most others. The findings show two ancestral frog’s genetic material wrapped neatly into one amphibian — essentially a two-in-one frog.
Most animals, like us, are diploid. We have two sets of chromosomes — one from our mother's and one from our father's. The X. laevis frog has four sets. This duplication created a puzzle. It made the decoding of the frog’s DNA more challenging as the four different versions of each gene had to be dealt with in the assembly.
“After we decoded a diploid frog relative back in 2010, our sights were set on X. laevis, but we knew it was tetraploid [four sets] and this made many think it might not be possible,” says Peter Vize.
Vize is a professor in the departments of Biological Sciences and Computer Science in the Faculty of Science with a cross appointment in the Cumming School of Medicine. The professor is also a member of the university’s Alberta Children’s Hospital Research Institute which has attracted a core of scientists who are using models to understand the mechanisms of human disease and find ways to improve diagnosis and treatment. The global research team published their findings this month in the journal Nature. The multi-centre study was led by the University of California in Berkley and the University of Tokyo.
The decoding of the genome revealed that this curious frog appeared on the planet approximately 17 million years ago. Two species of frogs mated and became a single species while retaining all four sets of chromosomes from the now extinct species. The team found that the chromosomes of each ancestral species could easily be identified by the mobile elements scattered along each DNA strand. Mobile elements are a type of DNA that can move around within the genome. Each frog genome had a different set of mobile elements.
This finding was a breakthrough that allowed the team to identify which sub-genome each assembled DNA strand belonged to, and solved the puzzle of how the tetraploid genome all fitted together.
"We knew that X. laevis had two versions of most genes, and that one was normally expressed more than the other, but until we could see the genome it was impossible to make sense of why this was so. Now we know that one ancestral genome was dominant while the other accumulated mutations and deletions. By knowing the chromosomal address, you can predict whether an alloallele will be more likely to be playing a dominant role, or if it is more likely to play a lesser role, or even have been deleted," says Vize.
Xenbase, a database for scientists worldwide
The Xenopus laevis has long been an important model in understanding developmental biology. It was part of 1992 experiments on the space shuttle Endeavour and it was also the first vertebrate ever cloned. The model is still used widely today in the context of health sciences.
Vize is one of the world’s experts in modelling the biological data of the Xenopus. He is the co-director of Xenbase, an international database used by scientists. The database, located at the University of Calgary, is funded by the U.S. based National Institutes of Health (NIH). The professor recently renewed a multi-million-dollar grant by the NIH to maintain and expand the database over the next five years. The grant is a collaboration between the University of Calgary and the Cincinnati Children’s Hospital Medical Center (CCHMC). The co-director of the project at CCHMC is Professor Aaron Zorn. The project has a computational component which is performed by a Calgary team and a data processing and curation component that is performed by the Cincinnati team.
Professor Vize is also supported by grants from the Natural Sciences and Engineering Research Council (NSERC).
The University of Calgary’s strategic research plan supports comprehensive, cross-discipline platforms on analytics and visualization of data to help problem-solving and decision-making. The platform integrates the efforts of researchers from different domains including arts, natural sciences, computer sciences, medicine, engineering, architecture, nursing and kinesiology that work in areas with a high potential for cross-pollination.