Modelling evolution on design-by-contract predicts an origin of Life through an abiotic double-stranded RNA world

BACKGROUND: It is generally believed that life first evolved from single-stranded RNA (ssRNA) that both stored genetic information and catalyzed the reactions required for self-replication. PRESENTATION OF THE HYPOTHESIS: By modeling early genome evolution on the engineering paradigm design-by-contract, an alternative scenario is presented in which life started with the appearance of double-stranded RNA (dsRNA) as an informational storage molecule while catalytic single-stranded RNA was derived from this dsRNA template later in evolution. TESTING THE HYPOTHESIS: It was investigated whether this scenario could be implemented mechanistically by starting with abiotic processes. Double-stranded RNA could be formed abiotically by hybridization of oligoribonucleotides that are subsequently non-enzymatically ligated into a double-stranded chain. Thermal cycling driven by the diurnal temperature cycles could then replicate this dsRNA when strands of dsRNA separate and later rehybridize and ligate to reform dsRNA. A temperature-dependent partial replication of specific regions of dsRNA could produce the first template-based generation of catalytic ssRNA, similar to the developmental gene transcription process. Replacement of these abiotic processes by enzymatic processes would guarantee functional continuity. Further transition from a dsRNA to a dsDNA world could be based on minor mutations in template and substrate recognition sites of an RNA polymerase and would leave all existing processes intact. IMPLICATIONS OF THE HYPOTHESIS: Modeling evolution on a design pattern, the 'dsRNA first' hypothesis can provide an alternative mechanistic evolutionary scenario for the origin of our genome that preserves functional continuity. REVIEWERS: This article was reviewed by Anthony Poole, Eugene Koonin and Eugene Shakhnovich