As elated as scientists were with the sequencing of the human genome in 2003, they soon recognized that it was only one important piece of a much more complex puzzle. Expecting to find at least 100,000 genes, they instead found just 22,000—too few to account for the remarkable complexity of human cells. What else was happening?
Brendan Frey and Benjamin Blencowe of the University of Toronto set out to solve the mystery of how humans can do so much with so few genes. What they found has revolutionized our understanding of how our bodies work and earned them the 2011 NSERC John C. Polanyi Award. Their research initially revealed that genetic messages produced from over 90 percent of human genes can be manipulated to do dozens, or even hundreds, of different things. They then deciphered the codes that instruct a gene to rearrange, or “splice,” its parts into different patterns to perform different functions. By deciphering this “splicing code,” the researchers also identified how DNA mutations that disrupt the normal set of codes can affect the normal functioning of cells.
Drs. Blencowe’s and Frey’s research teams co-developed new experimental and computational technologies that, when combined, generated a powerful framework for making accurate predictions about how parts of genes are rearranged to meet the needs of diverse cells—a process called alternative splicing. Their new technology can now be used both to identify the causes of diseases and to predict the outcomes of various treatments, which will accelerate the development of new therapies.
As they continue to unravel the riddle of the human genome, Drs. Frey and Blencowe, and their co-workers, will work to predict the outcomes of all possible splicing combinations and determine, in greater detail, how the process of alternative splicing generates the extraordinary biological complexity found in humans.