First Organism Produced with Expanded Genetic Alphabet

All of life, since its beginnings, has used DNA to encode genetic information. This code provides a blueprint for proteins, molecules that perform an enormous range of functions in an organism’s cells, and is passed on to the organism’s offspring when it reproduces. DNA can be recombined and mutated to allow for evolution of the way the organism operates on a molecular level and as such has produced all the wondrous diversity we find in nature.

All such DNA is built up out of just four distinct components, four letters that comprise the genetic alphabet: A, T, C and G. Proteins on the other hand are made up of 20 different components: amino acids. In order for the four-letter alphabet of DNA to encode 20 different letters in the protein alphabet, three letters are combined into a word, a codon. This makes for 64 different codons, enough to encode the 20 amino acids.

As far as we know, this genetic code is universal for life on earth. From humans to mice, from bacteria to viruses, all life on earth uses, and seems to have always used, this exact same code as its basis. Now, however, scientists have succeeded in expanding the genetic alphabet.

It’s known that components other than the A, T, C and G that make up ordinary DNA can be incorporated into a DNA molecule. However, putting such a modified DNA molecule into a living cell is another matter. Often, the cell cannot survive the modification, the modifications are removed by DNA repair mechanisms or the cell cannot copy the modified DNA and thus cannot reproduce anymore.

Now, however, researchers have succeeded in adding two new letters (with complicated names; let’s say X and Y) to the genetic alphabet of a real cell. They took E. Coli bacteria and modified their DNA to contain these new components; and the cells seem to suffer no negative effects. The modifications are not repaired by the cells’ correction mechanisms and, as long as they are supplied with enough X and Y (they cannot produce them themselves), they can copy the modified DNA and transmit it to their offspring. This makes them the first organisms on the planet with an extended genetic alphabet!

The possibility of creating such an organism opens up interesting possibilities. A genetic alphabet with six letters instead of four allows for more complexity (216 codons instead of 64) which could provide a new way to engineer the way the cells work. The added flexibility in the genetic alphabet may enable scientists to also introduce new amino acids to let the cells produce strange new proteins to perform customised functions.

The findings may also help figure out why nature chose the alphabet it did. Is there some reason the X and Y are not found in nature? Did nature simply not happen upon them? Is the additional complexity somehow not desirable? A lot of food for thought.


[1] D. A. Malyshev et al. A semi-synthetic organism with an expanded genetic alphabet. In: Nature 509, 385–388

Attribution: Featured image source: Wikipedia user Michael Ströck (link)

Marco is a theoretical (bio)physicist, currently engaged in unraveling the sequence-dependent dynamics of DNA molecules to earn his PhD at Leiden University. Other passions include literature and history.

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