Possible changes in fidelity of DNA polymerase δ in ancestral mammals

DNA polymerase {delta} (pol{delta}) is one of the major DNA polymerases that replicate chromosomal genomes in eukaryotes. Given the essential role of this protein, its phylogenetic tree was expected to reflect the relationship between taxa, like many other essential proteins. However, the tree of the catalytic subunit of pol{delta} showed an unexpectedly strong heterogeneity among vertebrate lineages in evolutionary rate at the amino acid level, suggesting unusual amino acid substitutions specifically in the ancestral mammalian lineage. Structural and phylogenetic analyses were used to pinpoint where and when these amino acid substitutions occurred: around the 3'-5' exonuclease domain in later mammal ancestry, after the split between monotremes and therians. The 3'-5' exonuclease domain of this protein is known to have an impact on the fidelity of replication. Based on these observations, we explored the possibility that the amino acid substitutions we identified in pol{delta} affected the mutation rate of entire chromosomal genomes in this time period.