“Chance and Necessity” on the Molecular Evolution of REV3 (a Catalytic Subunit of DNA Polymerase ζ)—The Dual Roles of Translesion and Neuronal Extension

Catalytic subunit of DNA polymerase ζ (REV3), involved in translesion-replication is evolutionarily conserved from yeast and plants to higher eukaryotes. However, a large intermediate domain is inserted in REV3 of humans and mice. The domain has “DUF4683” region, which is significantly similar to human neurite extension and migration factor (NEXMIF). This region was also found in REV3 of invertebrates such as Ciona intestinalis (sea squirt) … and Lingula anatina (Brachiopoda). We hypothesize foreign sequences were introduced into the Rev3 genes in the ancestral species of L. anatina, which would have gradually evolved into the DUF4683 region through overly complicated processes. Besides DUF4683, various exogenous sequences would have been inserted during the REV3 evolution. Therefore, insertion events of foreign sequences are all products of “necessity”. tBLASTn analysis of the Callorhinchus milii (elephant shark) genome with the C. milii REV3 sequence identified three neural factors (NEXMIF, NEXMIF-like and AHDC1) in distinct positions of the genome. These factors may have differentiated from the Rev3 gene in Chondrichthyes, which had experienced two rounds of whole-genome duplication, and may have evolved into neurite-forming proteins in vertebrates. L. anatina has the DUF4683 C-terminal proximal consensus (SPPRA/CWSP) in REV3. However, the consensus was not necessarily maintained in Mollusca, the closely related animal phylum of L. anatina. Just as written by Jacques Monod, we assume “chance” (mutation in DNA) and “necessity” (selection at the “organism” population level) were frequently repeated on the Rev3 in Cambrian ancestors. As a result, certain species developed the DUF4683 consensus of a neurite extension activity.