Monday, June 4, 2012

The alphabet to write DNA can be easily expanded

The genome, which is the entire collection of DNA that we possess, is an incredibly complex structure with tight regulation. Our DNA is divided over 23 chromosome pairs that each contain many genes that need to be read-out on an individual basis using a wide variety of regulatory molecules and proteins. The genetic code forms the instructions for life, which basically explains why it is incredibly complex. Nevertheless, DNA is pretty simple on a molecular level: it is 'written' using only four letters that match with each other in a specific way. Those letters are called A, T, C and G, and because the DNA structure consists of two entwining strings, A sits opposite of T, while C matches with G. All known forms of life are based on these lines of code, but scientists have discovered that it is relatively easy to add more letters to the DNA alphabet. This gives us more freedom to mess with the foundations of life and create our own applications, and possible even new life forms.

Scientists from the Scripps Research Institute set up experiments to evaluate whether DNA was 'open' to accepting other molecules that function as letters in the current four-letter alphabet. In a previous study, they already managed to create a so-called base pair. That means they matched two molecules together, much in the same way that A-T and C-G pair with each other. The two molecules, called NaM and 5SICS not only match together, but can also be replicated in the same way as DNA. Replication is an important process, as it allows for making copies of a string of code, which is necessary for creating new cells, or passing on the genetic code to offspring.
The way the four natural DNA letters are arranged. A and T, C and G pair together and form a typical double-helix structure. (source)
Building DNA
Next, the scientists set out to discover whether their additions to the alphabet could actually be used as fully-fledged DNA. That means setting up experiments to assess the behaviour of NaM-5SICS pairs. One of the most important features is being recognized by a molecule called DNA polymerase, which is involved with replicating DNA structures. Experiments point out that NaM-5SICS behaves in the same way as natural DNA bases, which is promising for artificial construction of genetic code. Because it works alongside conventional bases, we may be able to make artificial modifications to genes using our own letters.
From left to right: a double-stranded piece of DNA to be replicated. Helicase opens up the two strings in much the same way as a zipper, which reveals the molecular structure. Then, DNA polymerase comes along and attaches each base to its respective match: A with T, C with G. (source)
Hydrogen bonds are an
essential part of the DNA.
The base pairs A, T, C and G that make up natural DNA bind each other by using hydrogen bonds. This form of attachment was long thought to be an absolute necessity for the creation of DNA, because otherwise the replication process would not work. However, NaM and 5SICS bind in a different way, similar to what would happen if the DNA replication process results in a mismatch, for example an A binding with G, which normally are not compatible. Such events cause the replication process to halt to give specialized repair molecules time to fix the issue and re-match the mismatching pair. It is therefore most peculiar that NaM and 5SICS are able to integrate in the DNA without causing any trouble.

By adding new letters to the DNA soup, scientists gain more control over DNA modification. The NaM-5SICS pair is actually quite arbitrary, and it is likely to be possible to use other molecules as base pairs. If scientists succeed in creating more letters, we may be able to write our own book of life. And even though the code may be written in a 'foreign language', the tools that nature made to read the DNA and make proteins from it can be re-used, which means we would be well on our way to create artificial organisms. That will take more work, of course, as we have merely shown to be able to make a new letter. And creating one letter does not make a book.

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