UT Southwestern researchers find a previously unknown genetic code

UT Southwestern physiologists trying to understand the genetic code have found a previously unknown code that helps explain which protein should be created to form a particular type of cell.

The human body is made up of tens of trillions of cells. Each cell contains thousands of proteins, which determine how the cell should form and what functions it needs to perform. Proteins, in turn, are made up of hundreds of amino acids. The blueprint for each protein is specified by genetic codons, which are triplets of nucleotides that can make 20 different types of amino acids. The way in which amino acids are linked together then determines which proteins are eventually produced, and in turn, what functions the cell will have.

What researchers found was that not only does the sequence of the amino acids matter, but so does the speed of the process in which the amino acids are put together into a functional protein.

“Our results uncovered a new ‘code’ within the genetic code. We feel this is quite important, as the finding uncovers an important regulatory process that impacts all biology,” said Dr. Yi Liu, Professor of Physiology.

It was long known that almost every amino acid can be encoded by multiple synonymous codons and that every organism, from humans to fungi, has a preference for certain codons. The researchers found that more frequently used codons ? the “preferred codons” ? speed up the process of producing an amino acid chain, while less frequently produced codons slow the process. The use of either preferred or non-preferred codons is like having speed signs on the protein production highway: some segments need to be made fast and others slow.

“The genetic code of nucleic acids is central to life, as it specifies the amino acid sequences of proteins,” said Dr. Liu, the Louise W. Kahn Scholar in Biomedical Research. “By influencing the speed with which a protein is assembled from amino acid building blocks, the use of “fast” and “slow” codons can affect protein folding, which is the process that allows a protein to form the right shape to perform a specific function. This speed control mechanism makes sure that proteins are assembled and folded properly in different cells. Therefore, the genetic code not only specifies the sequence of amino acids but also the shape of the protein.”

The researchers found that proteins with identical amino acid sequences can have different functions if they are assembled at different speeds. This can have important implications for identifying human disease-causing mutations because this study indicates that a mutation does not have to change amino acid identity to cause a disease. In fact, most mutations in human DNA do not result in amino acid change.

“Therefore, our study indicates that the new “code” ? the speed limit of assembly ? within the genetic code can dictate the ultimate function of a given protein,” said Dr. Liu.

UT Southwestern Medical Center