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Sequencing the Canadian beaver genome

by Juanita Bawagan Feb 13 / 17
Researchers sequenced the genome for Ward, a 10-year-old beaver from the Toronto Zoo. (Credit: Toronto Zoo)

Canadian scientists have taken a deep look at one of their country’s most iconic animals using a technique poised to transform the way genomes are decoded.

CIFAR Senior Fellow Stephen Scherer led the all-Canadian team that sequenced the first genome for Castor canadensis, the Canadian beaver. The results were published in G3, a journal founded and edited by CIFAR Senior Fellow Brenda Andrews. Both are members of CIFAR’s Genetic Networks program.

“We can sequence genomes from any animal but we wanted to be a little more creative,” says Scherer, lead author of the paper and a molecular genetics professor at the University of Toronto. He chose the beaver both as a gift for Canada’s 150th anniversary and to “mark our territory.”

After starting his work, Scherer found out researchers in Oregon were working on what they called the North American Beaver Genome Project. Scherer challenged his team of molecular geneticists from the Centre for Applied Genomics at The Hospital for Sick Children and their Canadian collaborators to be first. Their test subject was Ward, a 10-year-old beaver from the Toronto Zoo. Six months after the challenge, Scherer’s team had completed the genome, and fully published their peer-reviewed results on Jan. 13. The Oregon team released an announcement about their genome sequence a day later.

Lok et al report the de novo assembly of the Canadian beaver genome, the first draft genome assembly for a large rodent. The beaver is an iconic national symbol for the sovereignty of Canada. The cover portrays the “3 pence beaver,” Canada’s first postage stamp issued in 1851 and reissued again 1852 in recognition of the beaver as the economic engine that drove colonial expansion leading to the founding of Canada. The stamp was designed by Sir Sandford Fleming, a proponent of the worldwide standard time zone, and Canada’s foremost railway engineer and distinguished scientist of the 19th century. (Credit: CS4 courtesy of MM).

“I would like to see more Canadian pet projects where we just do something for the sake of doing it. Generating knowledge, itself, is useful,” Scherer says. “I think CIFAR always encouraged that spirit.”

The beaver genome is composed of 2.7 billion base-pairs, which is slightly smaller than the human genome. These bases make up the genes that offer insights into the beaver and its intertwined history with Canada. For instance, researchers examined one gene related to teeth formation and found it was similar to a gene in the kangaroo rat. The discovery could help in understanding rodent evolution. Scherer says the beaver genome could also be an interesting area of “cultural genomics” to see how human interaction shaped the animal’s evolution.

Beyond a point of national pride, the beaver genome is the first mammalian genome to be sequenced using the de novo approach they developed. This method allows scientists to create a genome “from scratch” without relying on a reference genome. Scherer, who has devoted his career to studying the genomics of autism, believes it will be key to better understanding human diseases.

“Essentially, you don’t want to rely on what is already known. Because we know when you do that, you bias your interpretation and miss things,” says Scherer. 

The de novo method assembles the genome through a multi-layered approach. Researchers construct the first draft with long fragments of DNA and then flesh it out with shorter fragments. Next, they assemble the transcriptome – the sum of mRNA from blood and tissue samples – to serve as a scaffold for the genome. Finally, they compare it with related mammalian genomes and correct it manually.

De novo sequencing’s $20,000 price tag puts it out of reach for most people, but Scherer says this cost will only come down as technologies improve and usage becomes widespread. The de novo approach would be more accurate than re-sequencing and faster than fully sequencing genomes.

Scherer has started using this approach in families with multiple autistic children where no genetic alterations have been found. He hopes this approach will reveal genetic variants that standard testing may have missed. Eventually, he envisions a single technology that could not only capture all genetic variants but show how they are positioned in respect to other chromosomes. The de novo approach is a huge leap towards this end goal and will lead to many more discoveries, he says.

Canada’s 150th anniversary offers a chance to reflect on breakthroughs by Canadian scientists. For Scherer, the greatest influence was his mentor at Sick Kids, geneticist Lap-Chee Tsui. Competing in a worldwide race with bigger labs including biotech, Tsui discovered the gene responsible for cystic fibrosis in 1989. “Beyond the spectacular technology and science, for many of us of that generation, Tsui’s success reminded us that Canadians can come in first, and our beaver project serves as a 21st century reminder.”

 “We have cutting edge technologies here in Canada and we’re testing them continually on samples that are of interest to us — be it the diseases that affect our people or animals from our country,” he says.

“Doing experiments that are close to us, that we have added value in the interpretation, that’s what Canadians have always been good at.”

De novo genome and transcriptome assembly of the Canadian beaver (Castor canadensis)” was published in G3: Genes|Genomes|Genetics.