Rethinking nucleic acids from their origins to their applications

Abstract

Reviewed are three decades of synthetic biology research in our laboratory that has generated alternatives to standard DNA and RNA as possible informational systems to support Darwinian evolution, and therefore life, and to understand their natural history, on Earth and throughout the cosmos. From this, we have learned that: • the core structure of nucleic acids appears to be a natural outcome of non-biological chemical processes probably in constrained, intermittently irrigated, sub-aerial aquifers on the surfaces of rocky planets like Earth and/or Mars approximately 4.36 ± 0.05 billion years ago; • however, this core is not unique. Synthetic biology has generated many different molecular systems able to support the evolution of molecular information; • these alternatives to standard DNA and RNA support biotechnology, including DNA synthesis, human diagnostics, biomedical research and medicine; • in particular, they support laboratory in vitro evolution (LIVE) with performance to generate catalysts at least 10 4 –10 5 fold better than standard DNA libraries, enhancing access to receptors and catalysts on demand. Coupling nanostructures to the products of LIVE with expanded DNA offers new approaches for disease therapy; and • nevertheless, a polyelectrolyte structure and size regular building blocks are required for any informational polymer to support Darwinian evolution. These features serve as universal and agnostic biosignatures, useful for seeking life throughout the Solar System. This article is part of the theme issue ‘Reactivity and mechanism in chemical and synthetic biology’.