Dr. T. Ryan Gregory knows that size matters. Genome size, that is. But the nagging question is why?
"Why should some salamanders have 20 times more DNA than you and I do?" asks Dr. Gregory, a recent University of Guelph Ph.D. graduate and winner of the prestigious 2003 Natural Sciences and Engineering Research Council (NSERC) Howard Alper Postdoctoral Prize.
Much recent scientific research has focused on sequencing genomes, including the landmark 2001 draft blueprint of the human genome. The genome is all the DNA in the chromosomes of a particular species. But this DNA sequencing work is only serving to amplify another longstanding biological riddle. Since the 1950s, it has been clear that there is no obvious link between an organism's complexity and the size of its genome (also called its "C-value"), as exemplified by the salamander-human comparison. Seemingly simple organisms can have much larger genomes than complex ones. This finding was so counter-intuitive that, in the early 1970s, it was named the "C-value paradox."
This "paradox" dissolved with the discovery of non-coding, or so-called "junk," DNA. Only about 1.5 per cent of our DNA is made up of genes – the stretches of DNA that code for proteins. The other 98.5 per cent is non-coding. However, this insight only served to raise a much more complex puzzle that Dr. Gregory dubs the "C-value enigma."
"We still need to understand the mechanisms by which non-coding DNA is gained and lost, whether it has any biological effects, or even functions, and why some organisms maintain so much of it in their genomes, while others have remarkably streamlined chromosomes," says Dr. Gregory, who is already a world leader in the study of the evolutionary significance of genome size diversity.
During doctoral work at the University of Guelph with Dr. Paul Hebert (who sparked his interest in genome size research), Dr. Gregory drew together previously published research to compile the world's largest database of animal genome sizes. This online collection (http://www.genomesize.com) includes about 3,000 animal genomes and has become a critical resource for scientists worldwide, receiving up to 50 hits a day.
Using the database, Dr. Gregory did the first statistical analysis of large animal genome size data sets looking for any broad patterns. He's also using the database to make comparisons between genome size and such factors as cell and body sizes, and developmental and metabolic rates. For example, a genome's sheer bulk can influence the rate of cell division and thereby that of development.
The creation of the genome size database made it clear to Dr. Gregory that one of the major shortcomings of current comparative genomics is a serious lack of data about the genome size of invertebrates. Even though the number of invertebrate species far outnumbers vertebrates, the genome database contains more than twice as many entries for vertebrates.
As part of his Ph.D. research, Dr. Gregory used a new computerized image analysis technique (one that makes genome sizing faster and much less expensive) in an effort to right this taxonomic imbalance. He determined the genome sizes of about 400 previously unstudied invertebrates, ranging from insects to spiders to earthworms. At present, he's continuing this invertebrate genome work as an NSERC Postdoctoral Fellow at the American Museum of Natural History's Institute for Comparative Genomics (ICG), in collaboration with a team led by Dr. Rob DeSalle.
His long-term goal is to use these large-scale genome databases, in conjunction with new data sampled from a diverse array of animals, and concepts from fields as disparate as cell biology, physiology, and palaeontology, to help solve a biological enigma that has defied explanation for more than half a century.