Tracy Nguyen

Instructor: Malcolm Campbell

UWRIT 1103
November 10, 2016

Nature vs. Nurture: Could Mother Leave a Mark on Offsprings Epigenetics in The
Womb?

Every living matter has DNA, a universal template to store genetic material. Within DNA
are genes, which carry the instructions to create different proteins, forming phenotypes or
physical characteristics of an individual. DNA polymerase is an enzyme that helps with the DNA
copying process. However, genes are not the only factor that determines phenotypes, or the
physical appearance for what the genes code. There is a higher power that controls the activation
of those genes, called epigenetics. Epigenetics is the study of changes in organisms caused by
modification of gene expression rather than alteration of the genetic code itself. Epigenetics is
the reason why a skin cell looks different from a brain cell. They contain the same DNA, but
their genes are expressed differently. Some might be turned on or off at different regions of
the genes (Rettner). One example when epigenetics comes into action is the case where one of
the two identical twins develop cancer later on in life although they have the same set of genes.
The question is, how do people with the same genes result in different phenotypes?
People used to think that genes carried the instructions to make humans body. Not until
50 years ago when epigenetics was discovered and given a name, this belief persisted in the
scientific community. The Nature vs. Nurture debate regarding epigenetics has been raised since

the last century and many have been interested in the connection between motherss epigenetic
pattern and that of offspring. Could mother leave a mark on in-the-womb offsprings
epigenetics? In order to understand about epigenetics, we must understand the connection
between genes and gene expression.
So how does epigenetics have this power to control gene expression? According to an
interview with Dr. Dana Dolinoy, a post-doctoral researcher at Duke University, epigenetics
consists of molecular switches and markers, such as DNA methylation. Methylation is when a
methyl group attaches to a specific DNA, preventing DNA polymerase from performing its job.
A useful analogy is to imagine a strand of DNA is the code on a credit card, DNA polymerase is
a swiping machine, and the methyl group is a piece of gum that sticks on the credit cards code.
Without the methyl group, the DNA would smoothly slide through the DNA polymerase. With
the methyl group, DNA cannot slide through the enzyme as easily. And that DNA is never being
expressed. Now we are back to the cancer case question, how did it happen? A research team led
by Manel Esteller, director of the Cancer Epigentics and Biology Progam at the Bellvitge
Biomedical Research Institute, has identified an epigenetic change in the twin who would
develop breast cancer but not the in the healthy one. The team studied the levels of methylation
in the blood of 36 pairs of twins diagnosed with breast cancer or healthy. In each twin pair, they
analyzed and compared the genes to each other. They found out that in the potentially cancerous
twins, there was a higher level of methylation on the DOK7 gene, a gene that prevents tumor
formation (IDIBELL).
There was a study conducted on mice at the laboratory of Randy Jirtle at Duke University
by the team of Dr. Dana Dolinoy to show the effects of maternal diet had on offsprings
epigenetics. Mice were used widely in scientific research since their genome shared 99%

similarity with that of human. In this experiment, Agouti gene, a gene that makes mice appear
yellow and fat, was targeted. Initially, a mother mouse gave birth to one Agouti mouse and a
non-Agouti mouse, which was small and brown. Scientists in this team wondered what caused
the difference between these two mice although they were identical twins. Knowing the
methylation of epigenetics, they conducted a test to determine whether methylation played a role
in causing this difference. They exposed several mice when they were pregnant to a chemical
called bisphenil-A, or BPA. This chemical presents in many commonly used products, including
food and beverage containers, baby bottles, etc. When the mother mice were fed with BPA, they
gave birth to a significant amount of obese and yellow baby mice. This proved that the BPA
decreased methylation in the offspring and promoted the expression of the Agouti gene when it
was supposed to be off. The same team then started a second study in which they exposed
pregnant mice to BPA plus methyl nutritional supplement. Once they did this, they observed that
the offspring were no longer dominantly yellow and obese and there were more slender offspring
with brown coat. This indicated that maternal nutrient supplementation [could] counteract the
negative effects of exposure to that chemical (Chaddha).
At the end of World War II, because the German blockade cut off the food supply, a
German-occupied part of Netherlands had to face extreme hunger known as the Dutch famine of
1944-1945 or the Hongerwinter. The article provides an overview of the Dutch famine and the
consequences the famine left on the succeeding generations. The Dutch famine was a disastrous
event that happened on a well-nourished population. Because of its experimental characteristics,
the Dutch famine has been studied by many people (Schulz). It is a great example of how
epigenetics permanently alters gene expression after a generation-wide event. The famine mostly
affected health of unborn children during that time due to prenatal undernourishment. Studies

were conducted on children born within the famine years and who were born before that. The
effects of the famine appeared to depend on its timing during gestation, or the period when
embryo develops in the womb. Early gestation was thought to be the most vulnerable period.
People who were conceived during the famine were lighter at birth and more prone diseases later
in life, including diabetes. When the pregnant mothers faced famine, their bodies automatically
reduced the amount of insulin produced by using epigenetic markers to make a change in gene
expression, adjusting to the new diet. These expression patterns were then passed onto the
offspring while they were still in the wombs, causing the babies to be born with a low insulin
production rate. When the war ended, so did the famine and the babies grew up in a wellnourished environment. However, the problem sparked due to the fact that they had a low insulin
production rate from their mothers. Less insulin resulted in less glucose intake by the cells and
more glucose in the blood stream, which was the cause of diabetes (Moalem). These are all
products of the gene regulation mechanisms within our bodies in response to traumatic event.
Another mechanism epigenetics uses to control gene expression is histone modification.
DNA is normally tightly wrapped around a protein called histone. Without histones, DNA would
be too long to fit inside cells. When DNA replication occurs, DNA strands let go of the histones
and begin replicating. If histones squeeze DNA too tightly, the DNA cannot be read, meaning
it cannot expressed or being switched off (Rettner). Histone modification can be caused by a
placement of chemical groups such as methyl group (methylation), phosphate (phosphorylation),
or acetyl group (acetylation) (Histone Modifications).
Roughly a century and a half ago, said Timothy Erick, a Ph.D. candidate in Molecular
Biology, Cell Biology, and Biochemistry at Brown University, the field of biology was
consumed by a debate over the nature of evolution. According to Charles Darwin, whose theory

of evolution involved natural selection, the genome of an organism mutates at random and
mutations that lead to survival advantages are more likely to be passed down through generation.
Darwins opponent was Jean-Baptise Lamark, whose theory of evolution was linked to acquired
traits. He argued that organisms acquire adaptive traits during their lifetimes and these traits are
then being passed on to their offspring. The debate on the mechanism that drives evolution
decisively settled with Darwins victory; yet, biologists, psychologists, and everyone in the
scientific field have spent the last century debating a more clear-cut question: the influence of
Nature versus Nurture in the development of an organism from embryo to adult. The debate was
between advocates of genetic determinism, people who believe development is driven upon
hardwired genetic code, and advocates of environmentalism, people who believe development is
influenced by an organisms interaction with its environment. According to Timothy Erick, the
Ph.D. candidate, It is primarily the field of epigenetics that has shed light on the interaction
between nature (genes) and nurture (environment).
Epigenetics leads to individual differences in appearance, physiology, cognition, or other
phenotypic traits. The differences could easily be noticed in identical twins, ones whose genes
are completely the same. This is the nature aspect of epigenetic in the debate. Environment, the
nurture aspect, could also lead to changes in epigenetics. A study was conducted on over 160
women with this different breast tumor stages. Scientists were able to find the correlation
between lifestyle and the risk factor for developing breast cancer. They found that the P13 gene
in those with smoking and drinking habits was significantly methylated. The P13 gene is the
policeman gene that prevents cells from overgrow into a tumor. This proved that environment
factors could also influence a persons epigenetics (Christensen). The finding that life
experiences can induce epigenetic changes in individual organisms and their offspring alters the

way we think about the nature versus nurture debate, said Timothy Erick, the theories
proposed by Darwin and Lamarck are perhaps not as mutually exclusive as one believed. By
acknowledging the interplay of nature and nurture in shaping an organism, we will be able to
acquire a better understanding of our evolution.
So what is the role of epigenetics in the science field nowadays? Changes in gene
expression due to epigenetic mechanisms have been shown to link to diseases. According to
Peter Jones, director of the University of Southern Californias Norris Comprehensive Cancer
Center, among all the epigenetics research conducted so far, the most extensively studied
disease is cancer, and the evidence linking epigenetic processes with cancer is becoming
extremely compelling. Toshikazy Ushijima, the chief of the Carcinogenesis Division of
Japans National Cancer Center Research Institute said that epigenetic mechanisms were one of
the five most important considerations in the cancer field, and they account for one-third to onehalf of known genetic alterations (Weinhold). Strong links have also been found between
aberrant DNA methylation and aging - Jean-Pierre Issa, a professor of medicine at the University
of Texas M.D. Anderson Cancer Center, presented his finding at the a conference titled
Environmental Epigenomics, Imprinting, and Diseases Susceptibility held in Durham, North
Carolina. Some of the strongest, decade-old evidence shows progressive increases in DNA
methylation in aging colon tissues, and more recent evidence links hypermethylation with
atherosclerosis -Issa continued Altered, age-related methylation has also been found in
tissues in the stomach, esophagus, liver, kidney, and bladder. Much of Issas work focuses on
the connection between epigenetic process, aging, the environment, and cancer, and possible
ways to therapeutically reverse methylation linked with cancer (Weinhold). The Human
Epigenome Project was launched in 2003 in Europe. Peter Jones, director of the University of

Southern Californias Norris Comprehensive Cancer Center, shared that the Human Epigenome
Project was a lot more complicated than the Human Genome Project because theres only one
genome while there were plenty of variations of an epigenome in each and every tissue. The
Human Genome Project was a worldwide effort that took more than decade and billions of
dollars to map a whole humans genetic material (Weinhold). Once the Human Epigenome
Project completes its objectives, the final map will surely aid in preventing or finding cures to
diseases in humans.
Although one cannot control the working mechanism of epigenetics, lifestyle choice can
have significant effects on ones gene expression, hence the nurture side of the debate. Changes
in epigenetics are inheritable and a mothers choice of dietary can leave a mark on her offspring
as the above studies have proven; And so consciously being aware of this fact should prevent
pregnant women from doing anything that could potentially cause harm to their offspring.

Work cited

Chaddha, Rima. A Tale of Two Mice. PBS. 01 Jul. 2007. Web. 19 Oct. 2016.
Christensen, Brock C., et al. Breast Cancer DNA Methylation Profiles Are Associated with
Tumor Size and Alcohol and Folate Intake. PLOS, 29 Jul. 2010. Web. 9 Nov. 2016.
Erick, Timothy. Epigenetics: How Nurture Shapes Our Nature. Footnote1, 14 Nov. 2014.
Web. 19 Oct. 2016.
"Histone Modifications." What Is Epigenetics. N.p., n.d. Web. 05 Dec. 2016.
IDIBELL-Bellvitge Biomedical Research Institute. "Epigenetic difference in twins explains
different risk of breast cancer." ScienceDaily. ScienceDaily, 17 Oct. 2012. Web. 5 Dec.
2016.
Moalem, Sharon, and Jonathan Prince. Survival of the Sickest: a Medical Maverick Discovers
Why We Need Disease. New York, William Morrow, 2007. Print. 19 Oct. 2016.
Rettner, Rachael. Epigeentics: Definition & Examples. Livescience, 24 Jun. 2013. Web. 5 Dec.
2016.
Roseboom, Tessa, et al. Hungry in the womb: What are the consequences? Lessons from the
Dutch famine. Maturitas, vol. 70, no. 2, pp. 141-145. Science Direct. Oct. 2011. Web. 19
Oct. 2016.
Schulz, Laura C. The Dutch Hunger Winter and the developmental origins of health and
disease. Current Issue, vol. 107, no. 39. PNAS. 20 Sep. 2010. Web. 5 Dec. 2016.

Weinhold, Bob. Epigenetics: The Science of Change. Environmental Health Perspectives. N.p.
Mar. 2006. Web. 5 Dec. 2016.