FIGURE 4.1 Twelve possible nucleobases in a DNA- or RNA-based “alphabet” that can form specific base pairs within the constraints of the Watson-Crick base-pair geometry and artificially expanded genetic information system (AEGIS). Pyrimidine base analogues are designated by “py,” purine by “pu.” The upper case letters following the designation indicate the hydrogen-bonding pattern of acceptor (A) and donor (D) groups. Thus, the standard nucleobase cytosine is pyDAA, and guanosine is puADD.

Artificial chemical systems capable of Darwinian evolution have also been prepared from artificial laboratory genetic systems. Such systems were created in the laboratory by using an artificial DNA that contained six nucleotide letters rather than the four in standard terran DNA.6,7 These were chosen from the structures shown in Figure 4.1. The artificial systems can support the basic elements of Darwinian evolution (reproduction, mutation, and inheritance of mutated forms) even if the enzymes that support the evolution of artificial genetic systems are the natural terran enzymes that have evolved for billions of years to handle standard nucleobases.

Standard tools to detect genetic molecules are designed to detect standard DNA, containing the four nucleosides adenosine, guanosine, cytidine and thymidine. They cannot detect DNA built from nonstandard building blocks. This creates a special challenge for those seeking to design instruments to detect molecules on other bodies, such as Mars or Europa. Indeed, it is even possible that a form of life based on nonstandard genetic molecules might be present on Earth, undetected by standard tools that detect standard DNA.

Similar efforts in synthetic biology have shown that the ribose and deoxyribose sugars are not unique solutions to the need for a scaffolding in a linear genetic biopolymer. Starting in the 1980s, researchers in groups across the world—including the Benner and Eschenmoser groups in Switzerland, the Herdewijn group in Belgium, the Wengel group in Denmark, and most recently the Krishnamurthy group in La Jolla—have joined researchers in industry attempting to make nucleic acid analogs that might serve as drugs to determine what other types of sugars

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