Learning the Language of DNA
When one learns to write, they are first taught the letters of the alphabet. From there, they learn how these letters form words and then, how these words can be strung together to create sentences which have all sorts of meanings and functions. One important function is instruction. Sentences allow people to tell other people what to do and how to do it. They get things done.
Biology works in a similar way using DNA. Through DNA, cells are able to get instructions to do all sorts of things which allows one’s body to function normally.
In the past couple decades, scientists have been interested in the idea of learning the language of DNA, just like how one would learn English, in order to create instructions at the biomolecular level.
This would give scientists the ability to have precise control over the creation of biomolecules in the same way a cell does which would allow for all sorts of beneficial applications in fields such as medicine, material science and more.
This article tries to pinpoint and spotlight a few advances in the field and the potential benefits these advances might bring in the future.
The Syntax of DNA
To get started, a quick rundown of how DNA works as a language would be useful.
There are four letters of genetic code. A, G, C and T. From here there are codons which each consists of three letters in one of 64 combinations. These act as the words of genetic code. A string of these codons acts as the sentences and paragraphs in which useful instructions can be created.
From these 64 codons, there are 20 amino acids that can be created with each codon corresponding to an amino acid. Amino acids are then used to create proteins which are used as machines to create all the biomolecules in any living system.
Artificial synthesis of DNA involves unlocking the rules of this syntax to create instructions that are more catered to human needs.
Synthetic Genomes
One way in which scientists have been trying to experiment with DNA synthesis is by creating entire genomes from scratch. The first example of this was done in 2010 when scientists from JCVI used a mycoplasma bacteria as a container for an artificial genome. They destroyed the original DNA in this bacteria and inserted their artificial DNA making it the first cell with a fully synthetic genetic code.
The scientists wanted to go further and create a living organism with the simplest genome of any living thing which resulted in a cell containing only 473 genes. This differs significantly from bacteria cells which contain thousands of genes. While this was a great feat, the cell lacked the ability to divide on its own.
To fix this, the scientists added back 7 genes that allowed it to divide and reproduce like any other cell.
The goals of these minimalist experiments is to help figure out the relationship between individual genes in a cell and the function that that gene does. Studies like these will allow scientists to have more direct control over exactly what their synthetically created genomes are instructing cells to do.
Altering Species Genomes
Another example of utilizing DNA synthesis comes from Jason Chin and his team at the University of Cambridge. Back in 2019 they were able to recreate the genetic code of E. Coli from scratch creating significant changes to the code. This was another groundbreaking feat as it was the first synthetic creation of an already existing bacteria’s genome.
The reason for the significant changes was to make the genome more efficient. From the 64 possible combinations of genes there are many redundant combinations. Different genes can result in the same amino acid being formed which makes the language inefficient at utilizing all possible combinations.
To make this system more efficient Chin got rid of this redundancy and made it so that the genes could be used for more useful functions such as creating more “stop” codons which signal to the messenger RNA to stop protein synthesis.
The exciting thing about these experiments is the idea of using existing bacteria as factories for specific and useful biomolecules by altering their genetic code. An example of this can be seen from 2013 where altering the genetic code of yeast cells was used to create the antimalarial drug, artemisinin, at a much lower cost.
Changing the way DNA is Coded
Some really useful developments in this field is the potential of using codons of 4 DNA molecules rather than 3. This would open up the options of genes from 64 to 256. This shows how scientists could not only learn the language of DNA but also rewrite some of the rules themselves to better suit human needs.
Progress in this technique has been made by training tRNA to code for 4 letter codons through the use of directed evolution. This essentially involves the growth of tRNA molecules in generations where the molecules that are best at coding 4 letter codons are chosen for the start of the next generation. With each generation the molecules get better at coding for 4 letters rather than 3.
The benefits of having more gene options would be the ability to have cells create amino acids that aren't naturally found in proteins. The process essentially broadens the biological tool set.
One potential application could be more fine tuning when creating drugs for cancer treatments or other ailments. With more tools in the tool box, one has more options to make these drugs and drug delivery methods more safe and effective.
Conclusion
While this list is not exhaustive of all the advancements and applications in the field, it helps show the different routes people are going down and the different ways these routes can help create useful products and services.
Scientists are still a long way from being fluent in the language of DNA but just like any other language it takes time. And once they are fluent, they will be able to communicate with cells the same way one would a machine resulting in complete control of the biomolecular world.
