ABSTRACT

According to the RNA world theory for the origin of life, the first replicating molecules were nucleic acids, which had the ability to act as both a gene and a catalyst. A self-replicating biological system must have emerged from a non-living chemical system that was able to synthesize a mixture of random sequences. Here, we focus on three different ways in which an RNA sequence could be synthesized: (1) spontaneous polymerization of random RNAs from single nucleotides; (2) non-enzymatic replication, where a strand acts as a template for a complementary sequence; and (3) catalytic replication, where a polymerase ribozyme catalyzes the replication of a template strand. We refer to these as the s, r, and k reactions, respectively. The s reaction is non-living chemistry, the k reaction is living biology, and the r reaction falls in the gray area in between. We discuss the experimental evidence and the computational models that explain how RNA synthesis could have operated, aiming to address the question of whether polymerase ribozymes were required for the origin of life or whether some other kind of catalytic molecule could have come first.