Joined: May 2002
from nature science update:
Back two bases
Stripped down genetic code provides candidates for first molecules of life.
Chemists in the United States have constructed the simplest possible genetic language. Like Morse or binary code, it has only two letters - but it can orchestrate some of the basic molecular reactions needed for life to evolve.
This stripped-down genetic scheme might provide clues about how life began in the chemical soup of the early Earth, say its developers John Reader and Gerald Joyce of the Scripps Research Institute in La Jolla, California1.
Today, the recipes for life - RNA and DNA - are normally written in a four-letter molecular alphabet: the bases adenine (A), guanine (G) and cytosine ©, together with thymine (T) in DNA or uracil (U) in RNA. Each gene in DNA is a sequence of A's, G's, C's and T's.
But these bases aren't easy to make from the chemical constituents of the early Earth, point out Reader and Joyce. So they may not have been available to build molecules capable of carrying out the basic chemical processes of life, such as replication and catalysis.
A simpler two-base molecule might have stood a better chance, argue the duo. They have made a two-letter ribozyme - a molecule that helps another to stick to it. These catalysed link-ups are necessary to construct the molecular chains of the genetic molecules DNA and RNA.
Most biological catalysts, or enzymes, are proteins. But ribozymes are made from RNA. Because they can both catalyse reactions and hold and transmit genetic information, RNAs could have provided the molecular basis of life before proteins and DNA evolved.
Using just two bases, Reader and Joyce mimicked the R3 ligase ribozyme, a stretch of RNA that latches onto another RNA molecule.
Part of the R3 ribozyme has a base sequence that matches that on its RNA target molecule. The researchers constructed this binding sequence and target from A and U bases alone.
Then, for technical reasons, they replaced the A's with a non-natural base called diaminopurine (D). The resultant ribozyme can be copied without the need for G or C bases. Copying is a necessary part of the process of finding a two-letter mimic.
The researchers then eliminated all of the G's that they could from the R3 molecule while still retaining some of its catalytic behaviour (it can manage without C's). All but three could go; if the researchers took any of those out, the molecule was no longer catalytic.
To get further, the researchers abandoned rational design and turned to in vitro evolution. They replaced the remaining G's at random with U or D, while shuffling a few of the other U's and D's in the molecule.
None of the products made this way is a particularly stunning catalyst. But they work. The best, containing just U and D, links to the RNA target 36,000 times faster than in the absence of any catalyst at all. In other words, a two-letter ribozyme is a lot better than nothing.
D isn't too difficult to create from the kind of ingredients that were probably available on the early Earth, say Reader and Joyce. They also point out the advantage of an RNA-like molecule that contains no C: cytosine decomposes quite quickly if it gets warm.