title: Modelling evolution on design-by-contract predicts an origin of life through an abiotic double-stranded RNA world.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  This article was reviewed by Anthony Poole, Eugene Koonin and Eugene Shakhnovich.
authors.affiliation: Syncyte BioIntelligence, PO Box 600, 1000 AP Amsterdam, The Netherlands. albert.de.roos@syncyte.com
authors.forename: Albert D G
authors.initials: AD
authors.lastname: de Roos