The RNA-world hypothesis proposes that, before the
advent of DNA and protein life was based on RNA, with RNA serving
as both the repository of genetic information and the chief agent
of catalytic function. An argument against an RNA world is that
the components of RNA lack the chemical diversity necessary to
sustain life. Unlike proteins, which contain 20 different amino-acid
subunits, nucleic acids are composed of only four subunits which
have very similar chemical properties. Yet RNA is capable of
a broad range of catalytic functions. Here we show that even
three nucleic-acid subunits are sufficient to provide a substantial
increase in the catalytic rate. Starting from a molecule that
contained roughly equal proportions of all four nucleosides,
we used in vitro evolution to obtain an RNA ligase ribozyme
that lacks cytidine. This ribozyme folds into a defined structure
and has a catalytic rate that is about 105-fold faster
than the uncatalysed rate of template-directed RNA ligation.
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