Chapter 7, Problem 23P

In human DNA, 70% of cytosine residues that are followed by guanine (so-called CpG dinucleotides, where p indicates the phosphate in the phosphodiester bond between these two nucleotides) are methylated to form 5-methylcytosine. As shown in the following figure, if 5-methylcytosine should undergo spontaneous deamination, it becomes thymine.

 

a.	Methylated CpG dinucleotides are hotspots for point mutations in human DNA. Can you propose a hypothesis that explains why?	Making the simplifying assumptions that human DNA has an equal number of C–G and A–T base pairs, and that the human DNA sequence is random, how frequently in the human genome would you expect to find the base sequence CpG?
c.	It turns out that, even after taking into account the actual GC content of human DNA (˜42%), the frequency of CpG in human DNA is much lower than predicted by the calculation in part (b). Explain why this might be the case.