The team describes how a hidden code within DNA explains how a limited number of human genes can produce a vastly greater number of genetic messages. The discovery bridges a decade-old gap between our understanding of the genome and the activity of complex processes within cells, and could one day help predict or prevent diseases such as cancers and neurodegenerative disorders.
The researchers developed a new computer-assisted biological analysis method that finds 'codewords' hidden within the genome that constitute what is referred to as a 'splicing code'.
This code contains the biological rules that are used to govern how separate parts of a genetic message copied from a gene can be spliced together in different ways to produce different genetic messages (messenger RNAs). "For example, three neurexin genes can generate over 3,000 genetic messages that help control the wiring of the brain," says Professor Brendan Frey, from the University of Toronto.
When the human genome was fully sequenced in 2004, approximately 20,000 genes were found. However, it was discovered that living cells use those genes to generate a much richer and more dynamic source of instructions, consisting of hundreds of thousands of genetic messages that direct most cellular activities. Frey likens this discovery to "hearing a full orchestra playing behind a locked door, and then when you pry the door open, you discover only three or four musicians generating all that music."
"Previously, researchers couldn't predict how the genetic messages would be rearranged, or spliced, within a living cell," Frey said. "The splicing code that we discovered has been successfully used to predict how thousands of genetic messages are rearranged differently in many different tissues."
Citation: Barash et al., 'Deciphering the splicing code', Nature, May 2010, 465, 53-59;doi:10.1038/nature09000