FIGURE 1.

Hypothetical evolution of the vertebrate mitochondrial light strand replication origin, OL. (A) The presumed primitive step is polymerization initiated at stem-loop hairpins, such as those formed by DNA templating for tRNAs, which form more OL-like secondary structures in species whose mitogenome lacks a recognized OL. (B) DNA replication initiation gains specificity by adding a sequence motif near the hairpin, necessary for initiating polymerization, encountered in most vertebrates. (C) The next evolutionary state could be total loss of the stem-loop hairpin, where replication initiation depends solely on a linear sequence motif, potentially losing specificity, but clearly decreasing the length of the sequence required for replication initiation. Observations on replication in taxa lacking OL, such as birds, are compatible with this mechanism. (D) The linear motif punctuating polymerization initiation presumably becomes a translational signal. Indeed, 5′-GCCGG-3′ would code for alanine and glycine, the first amino acids integrated in the genetic code according to the consensual order of appearance of organic amino acids.