Modeling the origins of life: New evidence for an “RNA World”

Amazing stuff!

"... New research ... now provides fresh insights on the origins of life, presenting compelling evidence supporting the RNA World hypothesis. ... unveils an RNA enzyme that can make accurate copies of other functional RNA strands, while also allowing new variants of the molecule to emerge over time. These remarkable capabilities suggest the earliest forms of evolution may have occurred on a molecular scale in RNA. ..."

From the significance and abstract:

"Significance

An RNA enzyme with RNA polymerase activity was used to replicate and evolve an RNA enzyme with RNA-cleavage activity. The fidelity of the polymerase is sufficient to maintain heritable information over the course of evolution, with a succession of variants of the RNA-cleaving RNA enzyme arising that have progressively increasing fitness. The RNA-catalyzed evolution of functional RNAs is thought to have been central to the early history of life on Earth and to the possibility of constructing RNA-based life in the laboratory.

Abstract

An RNA polymerase ribozyme that was obtained by directed evolution can propagate a functional RNA through repeated rounds of replication and selection, thereby enabling Darwinian evolution. Earlier versions of the polymerase did not have sufficient copying fidelity to propagate functional information, but a new variant with improved fidelity can replicate the hammerhead ribozyme through reciprocal synthesis of both the hammerhead and its complement, with the products then being selected for RNA-cleavage activity. Two evolutionary lineages were carried out in parallel, using either the prior low-fidelity or the newer high-fidelity polymerase. The former lineage quickly lost hammerhead functionality as the population diverged toward random sequences, whereas the latter evolved new hammerhead variants with improved fitness compared to the starting RNA. The increase in fitness was attributable to specific mutations that improved the replicability of the hammerhead, counterbalanced by a small decrease in hammerhead activity. Deep sequencing analysis was used to follow the course of evolution, revealing the emergence of a succession of variants that progressively diverged from the starting hammerhead as fitness increased. This study demonstrates the critical importance of replication fidelity for maintaining heritable information in an RNA-based evolving system, such as is thought to have existed during the early history of life on Earth. Attempts to recreate RNA-based life in the laboratory must achieve further improvements in replication fidelity to enable the fully autonomous Darwinian evolution of RNA enzymes as complex as the polymerase itself."

Modeling the origins of life: New evidence for an “RNA World” - Salk Institute for Biological Studies Salk scientists unveil RNA capabilities that enable Darwinian evolution at a molecular scale, and bring researchers closer to producing autonomous RNA life in the laboratory

RNA-catalyzed evolution of catalytic RNA (no public access)