Bacteria Accept Expanded Genetic Code

Synthetic Biology: Researchers put DNA made from three base pairs—instead of the usual two—into living cells

Stu Borman

As life on Earth evolved, cells came to use two pairs of bases in their DNA: adenine and thymine, and cytosine and guanine. Those combinations have worked out pretty well for all living things. But this year Floyd E. Romesberg of Scripps Research Institute, La Jolla, Calif., and coworkers expanded the genetic repertoire by putting DNA with three pairs of bases into living bacterial cells (Nature 2014, DOI: 10.1038/nature13314). The new bases, called d5SICS and dNaM, pair up by hydrophobic interactions rather than by the hydrogen bonding used by natural DNA base pairs. Romesberg’s team found that natural bacterial DNA polymerase recognizes and copies the expanded DNA and that natural DNA repair enzymes don’t break it down. Expanded DNAs had been created, copied, transcribed into messenger RNA, and translated into nonnatural amino acids in proteins before. But they had never been put to work in living cells. If the expanded DNA could further be transcribed into messenger RNA in cells in vivo, the mRNA transcripts would have 216 types of codons (amino acid-coding units) instead of the usual 64, which could make it possible for the first time to insert several types of nonnatural amino acids into a single protein at once. Expanded DNAs could one day be useful for developing medicines, vaccines, and nanomaterials. Romesberg cofounded a company called Synthorx to look into such possibilities.

Modified bases d5SICS and dNaM pair up via hydrophobic interactions.

Modified bases d5SICS and dNaM pair up via hydrophobic interactions.

 A genetic alphabet with three base pairs instead of the usual two could lead to six-base mRNAs and more diverse proteins. A = adenine, C = cytosine, G = guanine, T = thymine, X = dNaM, Y = d5SICS. Credit: Adapted from Synthorx


A genetic alphabet with three base pairs instead of the usual two could lead to six-base mRNAs and more diverse proteins. A = adenine, C = cytosine, G = guanine, T = thymine, X = dNaM, Y = d5SICS.
Credit: Adapted from Synthorx

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