Complexities of gamete methylation:
A methyl group is a carbon atom with attendant hydrogen atoms fastened to some other chemical. When methyl groups are attached to genes they can alter the expression of the genes; this is a form of epigenetic control of what a cell does.
To the best of my understanding, methyl groups attached to DNA must have an adequate match between egg and sperm in order for there to be an organism with adequate fertility.
The pattern of methyl groups is passed from a cell to its daughter cells. This I would not have guessed. I thought maybe DNA, which is a double helix, replicated by unwinding and each strand served as a template for the complementary strand. I do not see how the methyl groups would get copied, but evidently they do. While the methylation pattern is fairly constant from one cell to its daughters, there is substantial change between generations. Again from my own impression, it is this change that produces the mismatch that can accumulate to have a significant effect on fertility.
I had read that before the DNA is packed into the sperm all methyl groups are removed. Yet the paternal pattern is detectable in the embryo. That does not make any sense either. Indeed a recent article (Zachary D. Smith et al A Unique Regulatory Phase of DNA Methylation in the Early Mammalian Embryo NATURE vol. 484 no. 7394 April 19, 2012 page 339) indicates that some methylation does persist in the sperm and makes no mention of any paradoxical reappearance.
That article describes doing full genome analysis on mouse sperm, ova and early embryos including exactly what is methylated. During this critical time, a large proportion of methyl groups are added and removed with different things happening at different times. The pattern of methylation is quite dynamic as the embryo forms.
That is quite consistent with what I had expected. There should be a lot of change. Of course they were not looking at fertility, and there is no mention of what the critical areas for our purposes might be, although clearly they analyzed the area of interest exhaustively.
So we have the old clause so beloved of the radiologist. “The study is consistent with, but not diagnostic of, a diagnosis of …” The new study does not confirm but does not conflict with my understanding.
Quite how one would pick out the critical methyl changes among the enormous number found is not clear to me at this time, but it is a task that I am sure will be performed some day.
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