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Like film editors and archaeologists, biochemists piece together genome history

Old-school Hollywood editors cut unwanted frames of film and patched in desired frames to make a movie. The human body does something similar—trillions of times per second—through a biochemical editing process called RNA splicing. Rather than cutting film, it edits the messenger RNA that is the blueprint for producing the many proteins found in cells.

In their exploration of the evolutionary origins and history of RNA splicing and the human genome, UC San Diego biochemists Navtej Toor and Daniel Haack combined two-dimensional (2-D) images of individual molecules to reconstruct a three-dimensional (3-D) picture of a portion of RNA—what the scientists call group II introns. In so doing, they discovered a large-scale molecular movement associated with RNA catalysis that provides evidence for the origin of RNA splicing and its role in the diversity of life on Earth. Their breakthrough research is outlined in the current edition of Cell.

"We are trying to understand how the human genome has evolved starting from primitive ancestors. Every human gene has unwanted frames that are non-coding and must be removed before gene expression. This is the process of RNA splicing," stated Toor, an associate professor in the Department of Chemistry and Biochemistry, adding that 15 percent of human diseases are the result of defects in this process.

Toor explained that his team works to understand the evolutionary origins of 70 percent of human DNA—a portion made up of two types of genetic elements, which are both thought to have evolved from group II introns. Specifically, spliceosomal introns, which make up about 25 percent of the human genome, are non-coding sequences that must be removed before gene expression. The other 45 percent is comprised of sequences derived from what are called retroelements. These are genetic elements that insert themselves into DNA and hop around the genome to replicate themselves via an RNA intermediate.

"Studying group II introns gives us insight into the evolution of a large portion of the human genome," noted Toor.

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