The explosive development of genetic technology is plain to see in Andrew Sharpe’s laboratory at the National Research Council’s Plant Biotechnology Institute in Saskatoon.
Three relatively new machines sit at the ends of three lab benches, crammed with sophisticated electronics and mechanics housed in the ubiquitous cream coloured plastic of the computer world.
A sticky note stuck to the side of one of the machines has the answer to a frequently asked question – how fast can these machines sequence base pairs, which are the rungs on the ladder of DNA, the chemical building block of life.
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Speed is important because it affects the pace of discovery in the new science of genomics – the road maps of all genetic material in all living things.
Every organism, from lowly bacteria to plants to humans, has a genome.
The sticky note says the three machines, working together 24 hours a day for one week, can sequence 17.7 million base pairs.
A few steps away, a newer machine similar in size to its older cousins can sequence 514.6 million base pairs in nine hours, which is about 500 times faster than the combined speed of the three old units.
The $600,000 machine will soon be obsolete as the technology leapfrogs ahead.
The term “paradigm shift” might be overused, but Sharpe said in this case it is apt.
“Ten years ago, even five years ago, you would never have contemplated such activities, but now we can do it,” said Sharpe, who moved from Britain to Saskatoon’s rising biotechnology scene in 1997 to pursue his science.
“It has really changed how we think about doing things. It’s a paradigm shift, or quantum leap.”
The Human Genome Project was a massive undertaking when it got underway in the 1990s, involving scientists at universities and government departments from around the world and costing billions of dollars. When completed in 2003, it was considered a scientific milestone on par with splitting the atom or going to the moon.
Today, technology advances are slashing timelines and costs, allowing genome sequencing to become a standard tool, even in plant breeding.
“Over time the technology will become cheaper and cheaper, so we will get on to routinely sequencing and resequencing any canola cultivar we want to,” said Sharpe, who leads PBI’s DNA Technologies Laboratory.
“That will ultimately be true for the majority of crops we grow today.”
Livestock genome mapping has its own story, but in crop agriculture, genome sequencing and mapping projects are already underway, or soon will be, in plant diseases, insect pests and weeds.
Farmers whose experience with genetic modification has been limited to crops with simple tolerance to herbicides and insects will, in coming decades, begin to see the full possibility of the science.
Complex traits such as tolerance to drought and frost stress and the promise of designer plants that were speculated about in the heady, early days of plant genetics will become possible.
To understand the possibilities, it helps to understand genes and the genome.
In 1953, James Watson and Francis Crick were the first to describe DNA, or deoxyribonucleic acid, the chemical compound that contains the genetic instructions for building, running and maintaining living organisms.
DNA molecules are made of two twisting, paired strands often called a double helix. Each strand is made of four chemical units, or bases: adenine (A), thymine (T), guanine (G) and cytosine (C). A always pairs with T and C always pairs with G.
The order of these four letters determines the meaning of the information encoded on parts of the DNA, in the same way that letters in the alphabet go together to make words.
An organism’s complete set of DNA contains billions of pairings of these four chemical bases. Sequencing means determining the exact ordering of the pairs on the DNA strand.
Each DNA strand, together with protein, forms a chromosome. Twenty-three pairs of chromosomes are located in the nucleus of human cells. Brassica napus canola cells have 19.
Some sections on DNA strands have no known function, but other sections form a unit, called a gene, which carries the instructions that cause other molecules in the cell to build proteins.
Some proteins make structures such as skin, leaves and roots, while others control chemical reactions and carry signals between cells.
Once a genome is sequenced, scientists start mapping out the locations and identifying the functions of the genes.
Isobel Parkin, an Agriculture Canada research scientist in Saskatoon and chair of the Multinational Brassica Genome Sequencing Project, said the genome map helps make the leap from basic science to useful purpose.
“They (genomes) are basically like roads and along these roads you have towns and landmarks along the way,” she said.
“We are trying to build a road map for canola.”
The map becomes more understandable as more landmarks are found. These markers are pieces of DNA near genes and can be traced from generation to generation.
“In the human genome project they identified markers across the genome in a very high density,” Parkin said.
“Once you have the density of markers across the genome, you can quite easily identify markers that are going to be closely linked to diseases of interest and any trait of interest. That opens a real bag of goodies as to what you can do.”
The technological advances that reduced the time and cost of genetic mapping have helped with the canola genome project because in some ways the oilseed’s genome is more complex than the human form.
Canola has 90,000 genes, compared to about 25,000 in humans, because brassica napus has the genomes of two related species: B. Oleracea, whose family includes cabbage and broccoli, and B. rapa, which includes turnip.
Sharpe said B. napus is a relatively recent creation, the product of human selection.
“Possibly a few hundred to a few thousand years ago they were growing turnips and cabbages together and by chance they crossed and we ended up with canola plants. They were selected and ultimately became a crop, but actually there are no wild populations in the world.”
The existence of two genomes means multiple copies of each gene, creating a lot of redundancy.
Dwayne Hegedus, an Agriculture Canada research scientist who works with Parkin, said the practical application of gene markers allows crop breeders to speed up their work.
“We are primarily interested in traits that improve the ability of producers to grow canola,” he said, citing programs in disease and insect resistance as well as quality characteristics.
“We can develop DNA markers that allow breeders to easily track those particular traits when they do crosses for breeding.”
Instead of creating hundreds of offspring from two parents and growing them in a greenhouse to see which ones carry the desired trait, DNA samples can be taken at the plantlet stage and through a quick genetic test determine which ones have retained the trait.
“We develop DNA markers that allow them to do it in probably an afternoon and you can do them on very small plants,” he said.
“It accelerates the breeding program tremendously.”
