New Letters in the Alphabet of Life

I have written earlier on why there are only four nucleotides in DNA, when a greater number would have meant a greater diversity in life forms. That nature has settled on four doesn’t have to mean that we can’t go for more.

Four nucleotides exist in pairs of two in a DNA. Triplet codons of these nucleotides code for 20 amino acids. Floyd Romesberg and team at the Scripps Research Institute have expanded the alphabets of the language of life to six with the addition of two unnatural base pairs (UBPs) – X and Y. Hopefully, it can code for as many as 172 amino acids which can be used to build a plethora of novel proteins. Xenonucleotides have been produced earlier too. But, they require totally new enzymes for their processing.

Six-letter DNA. Picture credits: The Wall Street Journal.
Six-letter DNA. Picture credits: The Wall Street Journal.

The major challenge for Romesberg’s group was the compatibility of the novel nucleotides with the replication, transcription and translation machinery of natural cells. The group had shown in 2012 that the six-nucleotide DNA was successfully replicated and transcribed in in-vitro experiments. But, this is the first time that artificial DNA has replicated in a living, reproducing organism. The team didn’t pursue the ideal case of engineering the metabolism of E. coli into making DNA with UBPs incorporated on its own. Instead, they grew it on a medium rich in precursors to the UBPs. The bacteria were found to grow slightly slower than normal. Also, it still hasn’t been successfully transcribed and translated inside a living cell.

Biosafety has long been an issue with synthetic biology. People have highly exaggerated fears of life being tinkered with in biotech labs. The bacteria with the artificial DNA have a built-in safety feature. It cannot create the artificial DNA outside the lab due to lack of UBP precursors.

Applications include better vaccines, new antibiotics, new cancer drugs, improved drug discovery, nanomaterials, diagnostics, forensics etc.


Romesberg. F. E., et al; A semi-synthetic organism with an extended genetic alphabet; Nature 509, 385–388 (15 May 2014); published online on 7 May 2014

Scientists create first living organism containing artificial DNA; Fox News



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