Discovery
of how environmental memories may be transmitted from a father to his
grandchildren
Newswise,
October 12, 2015 — If you have diabetes, or cancer or even heart problems,
maybe you should blame it on your dad’s behaviour or environment. Or even your
grandfather’s.
That’s because, in recent years, scientists have shown that,
before his offspring are even conceived, a father’s life experiences involving
food, drugs, exposure to toxic products and even stress can affect the
development and health not only of his children, but even of his grandchildren.
But,
despite a decade of work in the area, scientists haven’t been able to
understand much about how this transmission of environmental memories over
several generations takes place.
McGill researchers and their Swiss
collaborators think that they have now found a key part of the molecular
puzzle. They have discovered that proteins known as histones, which have
attracted relatively little attention until now, may play a crucial role in the
process.
They
believe that this finding, which they describe in a paper just published in Science,
has the potential to profoundly change our understanding of how we inherit
things.
That’s because the researchers show that there is something apart from
DNA that plays an important role in inheritance in general, and could determine
whether a father’s children and grandchildren will be healthy or not.
Taking
a new direction
In
the past, most of the research in this area, which is known as epigenetics, has
focused on a process involving DNA and certain molecules (known as methyl groups)
that attach to DNA and act a bit like a dimmer switch – turning up or down the
expression of specific genes.
The
researchers were curious about whether histones might play a role in
transmitting heritable information from fathers to their offspring because they
are part of the content of sperm transmitted at fertilization.
Histones are
distinct from our DNA, although they combine with it during cell formation,
acting a bit like a spool around which the DNA winds.
So,
to test their theory about the possible role of histones in guiding embryo
development the researchers created mice in which they slightly altered the
biochemical information on the histones during sperm cell formation and then
measured the results.
(It’s a bit like putting a nick in a spool of thread and
seeing how it affects the way the thread then loops around the spool.) They
then studied the effects on the offspring.
There’s
more than just DNA involved in inheritance
What
they discovered was that there were dire consequences for the offspring both in
terms of their development e.g. where offspring were prone to birth defects and
had abnormal skeletal formation, and in terms of their surviving at all.
Moreover, what was most surprising, was that these effects could still be seen
two generations later.
“When
we saw the decreased survivability across generations and the developmental
abnormalities we were really blown away as it was never thought that altering
something outside the DNA, i.e. a protein, could be involved in inheritance,” said
Sarah Kimmins, from McGill’s Dept. of Animal Science, and one of the lead
authors on the paper.
Kimmins is also the Canada Research Chair in Epigenetics,
Reproduction and Development.
Kimmins
added, “These findings are remarkable because they indicate that information
other than DNA is involved in heritability. The study highlights the critical
role that fathers play in the health of their children and even grand-children.
Since chemical modifications on histones are susceptible to environmental exposures,
the work opens new avenues of investigation for the possible prevention and
treatment of diseases of various kinds, affecting health across generations.”
Prof.
Marisa Bartolomei, Dept. of Cell and Developmental Biology, Perelman School of
Medicine, University of Pennsylvania
“While there is substantial evidence that fathers can transmit diseases and adverse phenotypes to their children in the absence of genetic mutations, this is the first study that shows a feasible mechanism by which this can happen. This gives researchers confidence to pursue histone retention in the male germ cells as a mechanism of inheritance....and it also will serve as a reminder to fathers to be diligent protectors of their germline.”
The
research was funded by: Canadian Institutes of Health Research (CIHR), Genome
Quebec, the Reseau de Reproduction Quebecois, Fonds de recherche Nature et
technologies (FQRNT), Boehringer Ingelheim Fond, Swiss National Science
Foundation and the Novartis Research Foundation.
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