Deamination

In the last section, we saw that as the replication fork expands, DNA polymerase synthesizes DNA quickly on the reverse half-strand but suffers delays on the forward half-strand. Notice that since the replication of a reverse half-strand proceeds quickly, it lives double-stranded for most of its life. Conversely, a forward half-strand spends a much larger amount of its life single-stranded, waiting to be used as a template for replication. This discrepancy between the forward and reverse half-strands is important because single-stranded DNA has a much higher mutation rate than double-stranded DNA. In particular, if one of the four nucleotides in single-stranded DNA has a greater tendency than other nucleotides to mutate in single-stranded DNA, then we should observe a shortage of this nucleotide on the forward half-strand.

Nucleotide counts of reverse and forward half-strands

Following up on this thought, let’s examine the nucleotide counts of the reverse and forward half-strands. The nucleotide counts for Thermotoga petrophila are shown in the below table. Although the frequencies of A and T are practically identical on the two half-strands, C is more frequent on the reverse half-strand than on the forward half-strand, resulting in a difference of $219518 − 207901 = +11617$. Its complementary nucleotide G is less frequent on the reverse half-strand than on the forward half-strand, resulting in a difference of $201634 − 211607 = −9973$.