Eutherians intrinsically run a higher risk of replication deficiency

Females inherit two X chromosomes from each parent, but males inherit only one from the mother. The POLA gene encodes the catalytic subunit of DNA polymerase α (pol-α), synthesizing a short DNA primer after RNA priming for DNA chain elongation in eukaryotic DNA replication. The POLA gene is established in the X-added region (XRA) of an X chromosome, translocated from a second autosome about 105 million years ago (mya). Dosage compensation for the mammalian X chromosome is accomplished by the silencing of one X chromosome to equalize gene expression between the male and female. We eutherians must replicate our DNA using pol-α expressed from a ‘single copy’ of genes, whose expression is probably reduced when chromosome translocation occurs. Spontaneous mutation occurring on the ‘single’ POLA gene, which decreases its replication fidelity, probably accounts for the increase of nucleotide substitution rates more effectively than in other organisms that possess the POLA gene on an autosome pair. Moreover, translocation of the POLA gene from an autosome to the X chromosome might reduce expression of pol-α, resulting in promotion of chromosome rearrangement. Therefore, the X-linked POLA gene possibly contributes to greater diversification of eutherian mammals.