Scientists have been twiddling with DNA for some time. While DNA may be the blueprint of life, it is not immutable (of course) and that means the hand of man likes to poke around in the mix. One kind of poking has been to see if one of the bases – adenine (A), thymine (T), cytosine (C), and guanine (G) – that make up the genetic code can be replaced. If it could be done while keeping the subject alive, it would constitute a new form of life.

This ‘swapping of bases’ is a trick that nature might have done. Last year (2010) there was a relatively well publicized rhubarb among scientists about the discovery of arsenic life by a team of NASA funded researchers; the team, which did not have to rely on the personal budget of one private donor or even one lab, was able to research a matter that may otherwise have been left untouched. They believe(d) they found a strain of bacteria living at the bottom of Mono Lake in California that due to a lack of phosphorus had substituted arsenic for phosphorus in key biological compounds (not in DNA but in ATP). [SciTechStory: An odd couple: Arsenic and life] The claim for arsenic life did not hold up too well under close scrutiny, but the mechanism at work, an evolutionary chemical substitution, is relevant to the current story.

In this case, an international group of researchers (Germany, USA, France, Belgium) looked at the structure of DNA and decided that if any base could be substituted, it would be thymine. (RNA already uses uracil instead of thymine.) They reckoned that 5-chlorouracil was chemically and structurally close enough to thymine to – perhaps – be taken up by DNA. Thus they began their experiments with the labster’s favorite bacteria, E. coli, by essentially putting it on a diet of nutrient spiked with chlorouracil and continually lowering the amount of thymine available.

As they reported in the journal Angewandte Chemie International Edition [27 June 2011, paywalled, Chemical Evolution of a Bacterium’s Genome] the substitution was accomplished by chemical evolution, where the absence of thymine caused the E. coli to start using chlorouracil and those bacterium that did thrived. This was evolutionary pressure at work, only with E. coli, which has a procreation cycle of about 4 hours, things happen relatively fast. The process was aided by the latest in automated monitoring and nutritional equipment so that the mix of chlorouracil and thymine was modulated to keep the E. coli population from declining too far but keep the pressure on to adapt to a chlorouracil-rich environment.

Within 23 days it was apparent that E. coli was taking up the chlorouracil replacement and the mix was accelerated. By 140 days the bacteria had substituted about 90% of its DNA with chlorouracil instead of thymine. The E. coli still require some thymine to live, but many interesting things happened to the DNA: The E. coli could successfully switch between thymine and chlorouracil, a number of chlorouracil mispaired with guanine, and in some cases the entire DNA structure was rearranged. As the researchers said, “It would have been impossible to predict the genetic alterations underlying these adaptations from current biological knowledge…”

E. coli with a 90% swap for chlorouracil is not a new life form; it still needs thymine to stay alive. However, it is a big step in that direction. Of course, as in so much of life, it’s the last step that’s the hardest. To finally produce a life-form that requires a different chemical for a DNA base has enormous implications. It would open the door to creating new organisms with all kinds of altered chemistry, while at the same time providing a built-in incompatibility with existing life. (We hope.)

For a more detailed description, check out Derek Lowe’s blog. In the Pipeline: A first step toward a new form of life