The Genetic Code Gets an Upgrade

This month, Jason Chin and his colleagues at the University of Cambridge reported that they were able to successfully upgrade the genetic code. This "new and improved" genetic code allows for the creation of completely new molecules, enzymes, and never-before-seen proteins. Theoretically, this "Genetic Code 2.0" could even be used as the blueprint for making new life forms.

Such news may seem the stuff of science fiction, but it's not. The standard genetic code is made up of nucleotides, which are essentially sugar-based molecules. There are four types of different nucleotides in deoxyribonucleic acid (DNA), which is the "blueprint" of life as we know it: adenosine, cytosine, guanine, and thymine. Ribonucleic acid (RNA), which is what DNA is transcribed to, also has these nucleotides, except that its thymine is replaced by uracil. DNA must be transcribed into the nucleotide language of RNA before it can be finally translated into protein.

Nucleotides are lined up three at a time in the genetic code to form what are called codons (i.e., coding sequence). For example, there is a codon made up of the sequence adenine-thymine-guanine, or ATG. The codon is first transcribed into RNA, after which it is translated into an amino acid. Amino acids are the building blocks of all proteins. Going back to the example of the codon ATG, that means that it is first transcribed into the RNA sequence adenine-uracil-guanine, or AUG, and then it is translated into the amino acid methionine.

Jason Chin and his colleagues took this process one step further: they created a genetic code that uses four nucleotides to make a single codon. For example, instead of having the sequence ATG be the codon for an amino acid, they made the sequence ATGC be the new codon for an amino acid.

Why is this significant? There are several reasons. The first one is that, when 3 nucleotides are mixed up into all sorts of combinations and orders, only 64 different codon combinations (e.g., CAA, ACA, AAC) are produced. However, when there are 4 nucleotides to mix per every codon, the possibilities go from 64 to 256.

This increases the possibility of making new amino acids, and thus new proteins, by a factor of 4.

However, when codons are being transcribed into RNA, and then that RNA is being translated into proteins, the process is not automatic. Various helper proteins and enzymes must be utilized along the way. One such helper protein is the ribosome. Ribosomes recognize RNA sequences and translate the codons into individual amino acids. Also, ribosomes have evolved to recognize 3 nucleotide-based codons, not 4 nucleotide-based codons.

To work around this issue, Chin and his colleagues mutated specific ribosomes in order to make them recognize these 4 nucleotide-based codons. Once this was completed, the mutated ribosomes could not only build proteins using the amino acids that are already prevalent in nature, but they could also build proteins from amino acids that were "unnatural", and never before used to make proteins.

These "unnatural" proteins have properties that are completely different from regular proteins found in today's life forms. For starters, the proteins are significantly more stable, thanks in part to the links between the amino acids being different. Stability is a key problem for proteins. For example, the protein found in egg white will unravel (denature) and become non-functional when exposed to heat. This is the reason why eggs whites that are cooked to 100C quickly turn from clear to opaque white. Proteins are also easily broken down to their component amino acids in the body. This is a problem if one is taking a drug that is protein-based; the effects of the drug are quickly undone when it is broken down into its basic, and thus non-functional, parts.

The "unnatural" proteins being produced by Chin's mutated ribosomes could solve a lot of the problems that are common to "natural" proteins. More stable proteins could lead to drugs that do not denature at high heat. These drugs would also be much more effective, since one would need to take just a small amount of a compound in order to have it work as a treatment. Repeated drug doses would become almost unnecessary, and so reduce the chances of liver and/or kidney toxicity.

Could Chin's expanded codon sequences and unnatural proteins be used to make new life forms? It's certainly a possibility. Even if the entire process never leaves the lab, novel proteins could be easily applied towards the building of macromolecules and bigger proteins. From there, cells could be constructed using these new building materials. Once cells are in place, tissues and organs could follow. Inevitably, a completely new living organism could result, with properties and strengths never before evidenced in nature.

While the reality of a better organism, or even a better human, has yet to be seen, it is a definite possibility.

References:

Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Heinz Neumann, Kaihang Wang, Lloyd Davis, Maria Garcia-Alai & Jason W. Chin. Nature advance online publication 14 February 2010. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08817.html#B8

Genetic code 2.0: Life gets a new operating system, by Linda Geddes. New Scientist, February 2010. http://www.newscientist.com/article/dn18523-dna-20-a-new-operating-system-for-life-is-created.html