It is not surprising that
we share 98.9% of our genome with chimpanzees.
It is challenging to consider that we have about the same number of
genes as mice and fish; but we have far fewer genes than plants. It is a high school science experiment to
extract DNA from strawberries. Rather than a double helix, their DNA is wrapped in a
quadruple helix. Obviously, the chromosomes and genes are only part of the
picture.
“Every time we see two things which are genetically identical, but which aren't the same, we're seeing epigenetics in action.” – Nessa Carey.
Epigenetics is often presented
as a new frontier in biology. In fact, the word originated in the 1940s; and
the first book came out a decade later. Following Crick and Watson, science
was focused on the chromosomes, and then on the genes. The Human Genome Project was declared to be successful
and the equivalent of Project Apollo, both for the complexity of the task and for its promise for our future. Enter
into your Web browser the phrase “scientists find gene for” and it would seem
that we are living on the Moon.
- The
Epigenetics of Birds by
C. H. Waddington (Cambridge University Press, 1952), reviewed by: J. T.
Marshall in Bios, Vol. 24, No. 1
(Mar., 1953), p. 59.
- Epigenetics.
A Treatise on Theoretical Biology by
Soren Lovtrup (Wiley, 1974), reviewed by Clifford Grobstein in The Quarterly Review of Biology,
Vol. 50, No. 4 (Dec., 1975), p. 439.
Ghost in Your Genes: PBS Nova (BBC 2006; WGBH 2007, 2008) delivers
graphic evidence that genetics is not heredity.
Identical twins raised in the same home diverge, one developing
autism. Twin sisters discover that one
has cancer, but the other does not. The
town of Överkalix in northern Sweden provided a paradigmatic story
of the effects of environment on heredity as grandparents who had suffered
starvation passed the consequences not to their children, but to their
grandchildren – depending on the sex of the ancestor and the sex of the
descendant.
The same differentiation was shown in the twins Jenna and Bridget.
Bridget’s autism is associated with a genetic deletion in Chromosome 15 - the ubiquitin-protein
ligase E3A (UBE3A) gene (Mayo Clinic here). It is called Angelman Syndrome. However, the same deletion is also associated with Prader-Willi
Syndrome, a form of obesity. The outcome
depends on whether the X-chromosome carrying it is inherited from the mother or
from the father. The chromosomes and
genes themselves are identical in both cases; the expressions are markedly
different.
“The route from genes to
morphological characters is convoluted and, in many aspects, still escapes us. This
is the reason why we have no hypothesis or model yet of the sequential steps of
the development of an organ. There is no evidence that any part of the genome
(a gene or a number of genes) codes or determines steps for developing a brain,
a heart, or even a strand of hair. It is true that genes or genetic networks
are involved or responsible for developing such characters, but their
involvement is not linear: a number of different types of cells have to be differentiated
and arranged in specific spatial patterns in order to form the organ. But both
cell differentiation (Christopher and Helin, 2010) and dedifferentiation (return
of cells to pluripotency) (Takahashi and Yamanaka, 2006), as well as activation
of gene regulatory networks (Cabej, 2010, pp. 23-24, 39-80), are epigenetically
rather than genetically determined. - Building the Most Complex Structure on Earth:
An Epigenetic Narrative of Development and Evolution of Animals by Nelson
R. Cabej (Elsevier, 2013, pg 67.)
As depicted in the PBS
Nova production, the Överkalix study revealed an array of distinctions laid
over the chromosomal inheritances. Diabetes,
early death, or longer life in the descendants depended on whether the affected
ancestor was male or female. Whether the ancestor was within the womb or
out also effected contrasting outcomes. Exactly when during gestation the event occurred also effected a different result.
Wikipedia has a bit more
to say. “The Överkalix study was a study conducted on the physiological effects
of various environmental factors on transgenerational epigenetic inheritance.
The study was conducted utilizing historical records, including harvests and
food prices, in Överkalix, a small isolated municipality in northeast Sweden . The
study was of 303 probands, 164 men and 139 women, born in 1890, 1905, or 1920,
and their 1,818 parents and grandparents. 44 were still alive in 1995 when
mortality follow-up stopped. Mortality risk ratios (RR) on children and
grandchildren were determined based on available food supply, as indicated by
historical data. Among the sex-specific effects noted; a greater body mass
index (BMI) at 9 years in sons, but not daughters, of fathers who began smoking
early. The paternal grandfather's food supply was only linked to the mortality
RR of grandsons and not granddaughters. The paternal grandmother's food supply
was only associated with the granddaughters' mortality risk ratio. … The father's poor food supply and the
mother's good food supply were associated with a lower risk of cardiovascular
death.”
In The Epigenetics Revolution (Columbia University Press, 2012),
virologist Nessa Carey tells a similar story from the Dutch Hunger Winter of
1945. “If a mother was well-fed around the
time of conception and malnourished only for the last few months of the
pregnancy, her baby was likely to be born small. If, on the other hand, the
mother suffered malnutrition for the first three months of the pregnancy only
(because the baby was conceived towards the end of this terrible episode), but
then was well-fed, she was likely to have a baby with normal body weight. … The
babies who were born small stayed small all their lives, with lower obesity
rates than the general population. For forty or more years, these people had
access to as much food as they wanted, and yet their bodies never got over the
early period of malnutrition. … Even
more unexpectedly, the children whose mothers had been malnourished only early
in the pregnancy had higher obesity rates than normal.” (pp 3-4). And this tendency to overweight was inherited
in the grandchildren (pg. 102).
Nessa Carey
has a virology PhD from the University
of Edinburgh . She worked
for five years at the Metropolitan Police Forensic Science Lab in London . (Her website is here.) In this book, she carries the analogy of a
Shakespeare play. The text of Romeo and
Juliet is the same for everyone. Almost every cell of your body has exactly the same chromosomes. (Red
blood cells and sex cells are exceptions.)
But you do not grow teeth in your eyes. The director’s comments,
distributed with the script, provide more information. Methylation and histone
deacetylations change the expressions of genes. Moreover, actors write notes in
pencil or attach Post-its. We smoke
cigarettes, drink alcohol, and ingest insecticides and herbicides. They affect us, of course, but it seems likely that they also affect our grandchildren.
These facts, should have
been the clues to scientists that the chromosomes, the genes, DNA and RNA must
be directed by other agents. Otherwise, as Carey says several times, you would
grow teeth in your eyes. By analogy to
the exploration of space, a series of giant steps over centuries allowed us to plot
the orbits of the planets correctly. The
work of Darwin, Mendel, Crick and Watson, the human genome project, all provided the
shoulders of giants for today's research. Epigenetic medicine
may be the equivalent of the Lunar colony.
ALSO ON
NECESSARY FACTS.
Disruptive Diagnostics and the Business of Science
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