Hypotheses for the origin of DNA. There is currently great uncertainty regarding the timing of the origin of DNA. This figure summarizes the different possibilities proposed in the literature. Scenario 1: Deoxyribonucleotides could have been synthesized prebiotically, and with the discovery that DNA can be made to carry out catalysis, it is not impossible to envision DNA emerging before RNA and proteins, though this idea is not widely accepted (reviewed in Dworkin, Lazcano, and Miller [2003]). Scenario 2: It has been suggested that deoxyribonucleotide synthesis could have originally occurred via a reverse of the deoxyriboaldolase reaction. In modern cells, deoxyribose-5-phosphate is broken down to glyceraldehyde-3-phosphate and acetaldehyde during salvage. The reverse reaction is energetically favorable and has been argued to be “easier” to evolve than protein synthesis (Benner, Ellington, and Tauer 1989), although it is not a feature of modern metabolism. Scenario 3: In modern cells, deoxyribonucleotides are synthesized by ribonucleotide reductases, which are ubiquitous and share a common origin (as evidenced by structure and conservation of key catalytic residues), despite differing biochemistries. This has been taken to suggest that the LUCA possessed DNA (Pode, Penny, and Sjöberg 2000). Scenario 4: DNA replication seems to have evolved twice, as the bacterial apparatus shares no homology with the archaeal/eukaryotic apparatus. It has therefore been suggested that LUCA possessed an RNA genome or, alternatively, a composite RNA/DNA genome (Leipe, Aravind, and Koonin 1999; Forterre 2002).