The DNA sequence itself
isn’t changing, but instead the expression of genes is altered, so different
amounts of proteins are being made. This
process is known as epigenetics (which I’ve discussed before with regard to
histone modifications). One way to
change DNA expression is by methylating cytosines (the “C” in DNA
sequences). The methyl group (CH3) makes
it harder for proteins to bind to the DNA and transcribe the genes into mRNA
and subsequently into protein. The
general rule of thumb is: more methylation --> less gene expression, less methylation --> more gene expression. This is a common way our cells regulate gene
expression, and what’s really interesting is that many external influences can
affect DNA methylation, like traumatic life experiences, smoking, exercise,
environmental toxins, etc.
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| Cytosine getting methylated (note the H3C addition on the the molecule on the right) |
It is conceivable that DNA
methylation patterns can be inherited through generations, so changes in gene
expression that affected your great grandparents could still be maintained in
your cells. Most of these types of
studies focus on changes that occur to the mom during pregnancy. For example, lets say that researchers expose
a pregnant mouse to a toxin that may affect DNA methylation. The next generation (the F1 generation) is
also being exposed in utero to the same toxin.
The eggs or sperm progenitor cells are also developing in the embryo, so
the next next generation (F2) may also be exposed to the toxin. Thus, if you see DNA methylation changes in
the F1 and F2 offspring, this isn’t really so surprising since these cells were
all exposed at the same time as the mom (F0 generation). In order to really prove that DNA methylation
patterns can be inherited across generations (transgenerationallly), you need
to expose the parents to a stimulus before conception, before the F1 and F2
generation even exist, which is what they did in this paper.
The authors chose to
initiate changes to gene expression by conducting odor conditioning in
mice. They paired a particular odor with
a mild foot shock and conditioned F0 males to be afraid of the odor. Then these males mated with naïve females
(never exposed to the odor). The F1
offspring showed excessive fear to the conditioned odor, even though they had
never encountered it before. It was
their fathers who had been shocked, not them.
The authors found there were more cells in the olfactory region of their
brains that expressed the olfactory receptor for the conditioned odor. Furthermore, their dad’s sperm and their own
sperm were less methylated in the gene that encodes for that particular odor
receptor, so the offspring of F1 were also affected.
F0 dad learns fear for odor --> decreased methylation for receptor gene --> F1 offspring inherit methylation changes --> express more of the receptor --> increased sensitivity to odor --> F1 sperm have same decreased methylation --> sensitivity for odor passed on to F2 generation
Grandpa (F0) had a bad experience with an odor and now his grandkids will be more afraid and sensitive to that odor. And it’s all genetic. The authors did a series of experiments to show that it isn’t behaviorally based (grandpa isn’t telling the grandkids about his horrible experience with this smell). For instance, they took the sperm from the F0 mice and took it to a different mouse facility and did in vitro fertilization, so the father was nowhere near his offspring or the mother. The F1 mice from in vitro fertilization were just as super sensitive to the odor.
Grandpa (F0) had a bad experience with an odor and now his grandkids will be more afraid and sensitive to that odor. And it’s all genetic. The authors did a series of experiments to show that it isn’t behaviorally based (grandpa isn’t telling the grandkids about his horrible experience with this smell). For instance, they took the sperm from the F0 mice and took it to a different mouse facility and did in vitro fertilization, so the father was nowhere near his offspring or the mother. The F1 mice from in vitro fertilization were just as super sensitive to the odor.
This is nuts!
