Figure 5

Intrinsic biases that favor accumulation of editing sites. In the CNE model (and, one might imagine, any model), new gRNAs (guide RNAs) arise fortuitously from anti-sense transcription of fragments of the parental gene. Initially, gRNAs are perfectly complementary to the mRNA of the parental gene: they play no role in editing and are subject to random loss. However, given a mechanism for editing the mRNA by inserting U’s complementary to A’s in the gRNA, the gene may evolve neutrally by events of mutation and random fixation that delete T’s, in which case the gRNA now becomes “functional”. A tendency toward accumulation of editing sites is expected due to biases in the introduction process. Initially, with 30 U:A pairs in the gRNA:mRNA region of complementarity, there are 30 ways to delete a T, each representing an evolutionary step toward editing. Once this happens, there is 1 way to revert, and 29 ways to delete a T, resulting in more extensive editing. Initially, increases in editing are favored, but over time, the system will equilibrate to an intermediate density of editing sites.