Nutrient availability can cause whole-genome recoding

PUBLIC RELEASE DATE:

9-Dec-2014

Contact: Kevin Jiang kevin.jiang@uchospitals.edu 773-795-5227 University of Chicago Medical Center @UChicagoMed

The availability of a trace nutrient can cause genome-wide changes to how organisms encode proteins, report scientists from the University of Chicago in PLoS Biology on Dec. 9. The use of the nutrient - which is produced by bacteria and absorbed in the gut - appears to boost the speed and accuracy of protein production in specific ways.

"This is in some sense a 'you are what you eat' hypothesis,"' said senior study author D. Allan Drummond, PhD, assistant professor of biochemistry and molecular biology at the University of Chicago. "This nutrient that is absorbed through the gut looks like it can cause the recoding of an entire genome over evolutionary time."

All known organisms store the blueprint of life in their DNA, and use the information to produce proteins - the structural components and molecular engines for almost every function in a cell. To accomplish this, copies of relevant DNA regions must first be made. These copies are strings of chemical letters that serve as instructions, and are read three letters at a time by molecules known as transfer RNA (tRNA). Each tRNA has a preference for a specific three letter combination, or codon, and is attached to a single amino acid. As the instructions are read, tRNAs sequentially bind to their corresponding codon and deposit their amino acid, creating a protein.

tRNAs possess a special property known as "wobble" - a flexibility in one of the binding positions - that allows them to pair with multiple codons. This means that different spellings of genetic code can be used to create the exact same protein, similar to how sentences can be written using different synonyms. However, this flexibility comes with a cost. Some codons are less reliably read and can introduce more mistakes. As such, certain codons are thought to be favored by natural selection.

To investigate the mechanisms that underlie this process and the evolutionary consequences, Drummond, together with Tao Pan, PhD, professor of biochemistry and molecular biology, and colleagues from Cornell University, analyzed and compared thousands of genes in a dozen different species of fruit fly. They looked for the frequency at which certain codons were used to encode proteins, and how this affected the accuracy and speed of protein production.

To their surprise, they found that the availability of queuine - a trace nutrient produced by bacteria that is only available when absorbed through the gut - played a major role in determining which codons were optimal. Flies which had abundant queuine possessed a higher proportion of tRNAs with a specific modification: a portion of their wobble-binding sites was replaced with a queuine-derived molecule known as queuosine (Q).

The team found that these Q-tRNAs were able to read and process certain codons much faster and more accurately than unmodified tRNAs, and caused changes throughout the flies' genomes. Species with access to plentiful queuine favored codon spellings that were optimized for Q-tRNAs. Species with access to less queuine favored other codon spellings.

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Nutrient availability can cause whole-genome recoding