Imagine a protein with functions that go beyond nature. Making proteins with unique molecules gives scientists more freedom to create new disease-fighting drugs. These proteins can now be easily made directly from a special genetic code.
Since the beginning of life as we know it, the genetic alphabet in all living things has consisted of four ‘letters’, representing the distinct molecules that make up the code of life: A, T, G, and C. Arranging them into 3-letter ‘words’ creates the code for amino acids, the molecules used to build proteins. But there’s a limit to the number of words that can be written with four letters, capping the amount of available genetic information.
Scientists at the Scripps Research Institute in California have rewritten the code – expanding it. They created two new letters (X and Y) to add to DNA, making a 6-letter code, and used this expanded code to add unique molecules into a protein. Adding new letters to expand the genetic code means significantly more information can be stored and used.
Illustration of a 6-letter DNA helix and the six letters arranged into three pairs. Image credit: thinkinghumanity.com.
For example, a 4-letter code provides 64 possible 3-letter words. There are only 20 amino acids, so multiple words match up with each. With the expanded 6-letter code, there are 216 possible 3-letter words, corresponding to up to potentially 172 amino acids – 8.5 times more than currently available.
Comparison of normal 4-letter DNA (top) and the new 6-letter expanded DNA (bottom). Image credit: sciencemag.org.
The expanded DNA is not made in a test tube, but inside a living organism – a bacteria to be exact. The team used the 6-letter code in bacteria to introduce new amino acids into proteins for the first time. The scientists actually created the expanded code in 2014, but bacteria could not read the newly created words. Now, their new letters are readable in a living organism.
This technology can be used to make new drugs, materials, and even life forms. “[This] is likely to be just the first of a new form of semi-synthetic life that is able to access a broad range of forms and functions not available to natural organisms,” the scientists remarked in their paper.
This breakthrough development will be crucial to making proteins with new functions directly in living organisms.
The scientist who led this research, Floyd Romesberg, said “every protein produced in any living cell has been produced by decoding a four-letter alphabet. We have now reported the decoding of proteins with a six-letter alphabet. … That still makes the hair on the back of my neck stand up.”
“The immediate goal that really drives us is to use the semi-synthetic organism to create new classes of protein drugs,” Romesberg added. Protein drugs, such as insulin, have revolutionized medicine. They are currently made in cells, using nature’s efficiency to our advantage. But nature’s limited number of amino acids also means limited protein properties and treatable diseases. Incorporating amino acids with new functionality not only allows for development of new protein drugs, but for production of those drugs more cheaply at a larger scale using these modified bacteria.
Creating genetically modified bacteria might sound like a Frankensteinian endeavor, but it’s not as worrisome as it sounds.
“These organisms cannot survive outside the laboratory. Personally, I think it’s a less dangerous way to modify DNA [than existing genetic engineering],” says Eric Kool, a biological chemist at Stanford University who was not involved in this study.
These bacteria are harmless because they cannot make the new letters on their own. The letters must be provided for the bacteria to survive and are not found in nature, giving scientists control over the bacteria. Carefully controlling genetically modified organisms (GMOs) is important for preventing their escape into the environment.
Although this research has far-reaching ethical and regulatory implications, don’t expect genetically modified humans with an expanded genetic code anytime soon – Frankenstein is still just a figure in science fiction. But do expect these genetically modified bacteria to help humans conquer disease and learn more about the code of life.
This article has been modified from the post Expanding the genetic alphabet, which originally appeared on Science in the News.
Advertisements Share this:
