DNA with Man-Made Bases Functions Just Fine

These “unnatural base pairs” are a first for synthetic biology

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The genes that direct all life on earth employ just four base units: A is for adenine, which bonds with thymine (T). G is for guanine, which bonds with cytosine (C). Combinations of A, T, G and C appear in each and every living thing—and now scientists have added two new letters to the alphabet. These unnatural base pairs are a first for the burgeoning field of synthetic biology.

In 2008 a team of chemical biologists at the Scripps Research Institute in La Jolla, Calif., began experimenting with compounds that could serve as new bases for the genetic code, a dream of some scientists since the 1960s. They found that two in particular— d5SICS and dNaM—worked well with the enzymes that read or copy DNA in living organisms.

So the team inserted these unnatural base pairs into a plasmid, a short sequence of free-floating DNA that can persist inside a cell, and put that plasmid into the microbe Escherichia coli. The addition went well: the E. coli happily copied the unnatural base pairs and its internal DNA editors, which usually get rid of oddities, did not notice them, either. Despite the alien DNA inside, new daughter cells had no trouble growing. The team published the results in May in Nature. (Scientific American is part of Nature Publishing Group.)

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Next, the researchers aim to get the unnatural base pairs into the actual genome of a microbe rather than an adjacent plasmid. If they can do that, they might be able to get the unnatural base pairs to code for genes that produce new compounds, such as amino acids that could be useful in medicine or other areas. Jargon to watch for in the future may include such terms as “unnatural amino acids.” Regardless, the genetic alphabet has now gotten a bit longer, which means that, in principle, the book of life can be rewritten.

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