Scientists Uncover Hidden Feature of Genetic Code to Control Protein Production

It turns out there's a new way to reprogram bacteria that could revolutionize the way scientists create new drugs and biological devices. Researchers have uncovered a hidden feature of the genetic code that could control how much protein that a bacterium produces.

In order to manage the new technique, the scientists combined high-speed DNA sequencing and DNA synthesis technologies. More specifically, they found that using more rare words, or codons, near the start of a gene removes roadblocks to protein production. In order to produce a protein, a cell must first make working copies of the gene encoding it. The copies, called messenger RNA (mRNA), consist of codons.

In bacteria, some codons are used more often than others. These rarer codons, though, appear more frequently at the start of a gene. In addition, genes whose opening sequences have more rare codons produce more protein than genes whose opening sequences do not.

In order to examine this process, the researchers tested how well rare codons activated genes by mass-producing 14,000 snippets of DNA with either common or rare codons. The scientists spliced them near the start of a gene that makes cells glow green and inserted each of those hybrid genes into different bacteria. They then grew the bacteria, sorted them into bins based on how intensely they glowed and sequenced the snippets to look for rare codons.

What did they find? It turns out that genes that opened with rare codons consistently made more protein. In addition, a single codon change could spur cells to make 60 times more protein--a big deal for the cell.

"These findings on codon use could help scientists engineer bacteria more precisely than ever before, which is tremendous in itself, and they provide a way to greatly increase the efficiency of microbial manufacturing, which could have huge commercial value as well," said Don Ingber, Whyss Institute Founding Director, in a news release. "They also underscore the incredible value of the new automated technologies that have emerged from the Synthetic Biology Platform that George leads, which enable us to synthesize and analyze genes more rapidly than ever before."

The findings are published in the journal Science.