Replication of Information on the Prebiotic Earth.

The origin of life consisted of several major transitions involving nucleic acids. Initially, chemical processes must have given rise to functional nucleic acid sequences (e.g. ribozymes). However, all replication is subject to mutation and this sets a theoretical limit on the maximum genome length. If a sequence is longer than this maximum length, runaway mutations destroy the information in subsequent generations. This raises a dilemma during the origins of life, because the high mutation rate of non-enzymatic replication has been thought to prevent the initial emergence of sequences long enough to encode enzymes (Eigen’s paradox). We reconsider this paradox in light of realistic dynamics of nucleic acid replication. In particular we found that chemical polymerization stalls dramatically after an error, effectively slowing down the production of mutant sequences relative to perfect copies. As a result, the accurate copies can begin a second round of replication more quickly. We determined mutation rates and quantified stalling in an experimental model system for non-enzymatic nucleic acid replication. Mutations slow extension by more than two orders of magnitude on average. We modeled these dynamics and show that the maximum theoretical genome length is substantially increased. Thus, despite a high mutation rate (7.6  1.4%), non-enzymatic replication could potentially give rise to sequences long enough to encode a ribozyme. 

According to the well-accepted ‘RNA world’ theory, a very early stage of life was dominated by RNA, which acted as both the genetic material and as chemical catalysts. Therefore, a second major transition during the origin of life was the ‘genetic takeover’, when DNA became the carrier of genetic information. This would have enabled the transition of the RNA world to the DNA-RNA-protein world of today. To understand the implications of the genetic takeover for information storage, we compared the intrinsic susceptibility of RNA and DNA to replication errors. Our results demonstrate that RNA is intrinsically error-prone compared to DNA and that this is largely because of the stability of G-U wobble pairs in RNA. In addition, we also characterized the RNA-DNA hybrid systems and found that while RNA can be copied into DNA fairly accurately, copying DNA back to RNA would be quite inaccurate, making the transfer of information from RNA to DNA essentially irreversible. Our results suggest that the ‘genetic takeover’ by DNA would permit an increase in genomic information content thus conferring an evolutionary advantage to organisms that utilized DNA as the genetic material. These projects improve our understanding of two major transitions during the origin of life: the emergence of the first ribozymes, and the subsequent transfer of information to DNA.