Prof will also lend his expertise in genome sizes to the DNA bar-coding program run by his former PhD supervisor
BY ANDREW VOWLES
It was one of the biggest surprises to come out of the Human Genome Project. When scientists began their ambitious initiative in 1990 to sequence the entire human DNA library, they had expected to find anywhere from 60,000 to 120,000 genes, says Prof. Ryan Gregory, Integrative Biology. But by the time they read the final snippet of DNA in fall 2004, that number had shrunk to a mere 20,000 to 25,000 genes.
That result didn't necessarily shock a scientist who had already run across plenty of surprises and puzzles while studying genome sizes at Guelph and elsewhere. Never mind sequencing genes: Gregory had already figured out that studying the total amount of DNA — genes and more — in the world's organisms and implications from genome structure to evolution would offer plenty of scope for a research career.
That's what he plans to do as a recently appointed professor at his alma mater and as head of genomic diversity at the planned Biodiversity Institute of Ontario (BIO), currently being built across Gordon Street from his Axelrod Building office.
Gregory will also lend his expertise in genome sizes to the DNA bar-coding program run by his former PhD supervisor, Prof. Paul Hebert. Together they wrote the funding application that yielded a $5-million Genome Canada grant this summer for continued studies of telltale DNA stretches used like supermarket bar codes to identify species of living things.
“It's going to be very exciting,” he says, referring to his planned role at BIO. “It's going to be unlike any other institute. There are other biodiversity centres, but none with such a broad view.”
Genome size matters in a number of ways. In agriculture, differing amounts of genetic material may help certain plants adapt to colder temperatures. In human health, scientists believe transposable elements — mobile stretches of DNA making up large portions of the genome — can cause mutations and are implicated in certain diseases.
Gregory's studies will also feed into genome sequencing projects of other scientists. Genome size directly affects the cost and difficulty of those projects.
“In fact, genome-size information is now considered a prerequisite by many of the agencies that provide funding for large-scale sequencing initiatives,” he wrote in an article published this fall by Nature Reviews Genetics.
His primary interest lies in implications for evolutionary theory. “Viewing the genome as a sort of genetic ‘ecosystem' shows how some DNA elements survive and reproduce better than others, just as do certain organisms within populations.”
And because genome size also affects such features as cell and body size, metabolic rate and development, processes occurring within the genome have consequences at other levels.
The question of why different organisms vary widely in amounts of DNA (also called “C-values”) has preoccupied biologists for decades. Especially intriguing was the observation that a more complex creature like a human didn't necessarily have more DNA than, say, a salamander. Scientists even labelled the apparent disconnect as the C-value paradox.
Studies in the 1970s and '80s found that genes were separated by lengthy stretches of non-coding DNA, a result that effectively settled the so-called paradox. In fact, genes coding for proteins make up only about 1.5 per cent of the entire human genome.
“You don't need a lot of genes to make even the most complicated types of organisms,” says Gregory.
But resolving the paradox only led to new questions. What was in those non-coding sequences? How were those sequences gained and lost over evolutionary time? How did carrying so much non-coding DNA affect organisms? Calling these and other questions the “C-value enigma,” he says: “It relates to one of the most fundamental properties of genomes, yet it's one of the longest-running puzzles in genetics.”
Those are the kinds of questions he plans to address back at Guelph. It was here that he became interested in the field. He'd actually been studying biology at McMaster University, where he attended a seminar given by Hebert. Gregory's post-lecture questions drew an invitation to visit the Guelph scientist's lab, where they first discussed genome size.
As Hebert's PhD student, Gregory began an ambitious project to assemble new and known genome sizes for various animals. So far, the resulting Animal Genome Size Database contains information for just over 4,000 species — a tiny fraction of the estimated 10 million species worldwide but still the largest collection for animals. (A similar repository maintained by the Royal Botanic Gardens at Kew contains data for almost 5,000 plant species.) That online database is already a well-used resource for other scientists, but Gregory hopes updates will make it more widely accessible.
Based on his student work, he received the 2003 Howard Alper Post-doctoral Prize from Science and Engineering Research Canada. This year, he received the Arch Award for distinguished young alumni from McMaster. He worked at the American Museum of Natural History in New York and the Natural History Museum in London before returning to U of G last year as a research associate. He joined the faculty this summer.
This year saw publication of his first book, The Evolution of the Genome, edited by Gregory and containing chapters written by experts worldwide. He has also published more than 30 scientific articles.
Gregory says what excites him most about returning to Guelph is that “I feel I am finally getting started. All that preparation is coming to fruition.”
