In my last discourse, I explored the capacity of the human brain for evil - whether or not all human beings as a species, possess an innate propensity to it (evil) as held by the German Philosopher Immanuel Kant, but above else, whether or not, that propensity, like some ineradicable mark of Cain is pre-determinedly and randomly implanted in the neurons of our brains at birth, so that we cannot help being what we later become.
It was a discussion which followed from my overall interest in the contentious behavioral dichotomy of humans; and was the first part of a long series in which I plan to explore the diverse array of forces shaping the individual development of human brains, bodies and behaviors.
In this discussion, I continue that exploration, this time into the field of genetics.
DNA may provide a genetic plan for you, but several factors affect how that plan will be expressed (License: Public Domain):
Creative Commons
Let me start by asking: What if there was a pill you could at will just take to block or unblock a select combination of genes to improve your health status, generally, your quality of life?
What if by simply taking a pill, you could turn off aging?
Overall, what if you could fine-tune your genome so to decide the phenotype?
Those are no doubt mouthwatering possibilities; they are a fundamental part of the latest research in the field of genetics.
First however, we must reflect on the basic questions of genetic identity. What makes a person X different from a person Y? Consider identical twins, if they inherit the same set of genes, you know - if they are made up of the same genetic building blocks, how can they be so different – in personality, in health, and with age, even in appearance?
Identical twins with same genes can have different personalities:
Creative Commons
Why are some people shy and others bold, pessimistic and others optimistic?
What produces that variation? Is it a result of some sort of a genetic lottery?
Here an excess of dopamine ensures that a person X becomes a drug addict and there, a shortage of it ordains that a person Y grows to be shy?
Or is it that this variation follows from a genetic legacy, handed down as a template from an ancestral lineage?
Granted, evolution ultimately produces the variance that becomes most successful, but how about the grist of the mill? Overall, why do we grow up to have the traits that come to define our adult lives, and that effectively ensure one person comes to differ from the next?
An old-age adage for contemplating these questions is perhaps best illustrated by Dan Hurley’s fictitious conversation in his 2013 article, Trait vs. fate.
In it, Charles Darwin, who first formulated the theory of evolution by natural selection in his 1859 book: “On the Origin of Species”, pg 162, and Sigmund Freud, the psychoanalyst who postulated the theory of psychosexual development which partly alludes to how one’s morals and values follow from parental influence, walk into a bar.
At the bar, Darwin and Freud meet two alcoholic mice, one a mother mice and the other, her pup son sitting on two stools, and lapping gin from two thimbles.
“Hey, geniuses", the mother mouse asks, looking up at them, "tell me how my son got into this sorry state.”
How did this pup get into this sorry state?
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“Bad inheritance,” Darwin answers.
“Bad mothering,” Freud counters.
And there you have it. Two views – nature (inheritance) and nurture (mothering)
Opposing explanations of how behaviors develop, how they modify and how they eventually persist, within an individual.
‘Nature’, following from these two opposing views, alludes to the genes, to a person’s genetic code, comprised of roughly 3 billion building block molecules (nucleotides) of DNAresident inside the nucleus of a cell, the master program at the center of every minute piece that makes us who we are.
Nurture meanwhile alludes to our environments, all of a person’s life exposures and experiences starting from the utero where sits the fertilized egg through birth and childhood to advanced aging. All of these influence one’s genetic potential by regulating the degree to which individual genes are expressed.
To the enduring dilemma of how as humans, we come to have the traits we do, either of these two theses – nature and nurture – have been part of the still incomplete answer. Why are you the person you are today? In simple terms, is it because you were born that way and can’t help it, or is it because of the environment in which you were raised?
An important part of the solution to this dilemma, research of the last decade however suggests, is epigenetics – nurture shaping nature.
What is Epigenetics?
Epigenetics is typically defined as the study of heritable changes in gene expression that are not due to changes in the DNA sequence.
Epigenetic Mechanisms (License: Public Domain): Wikimedia Commons
As important as which genes a person has (and what environments one such person encounters) is how his or her genes are affected by their contexts.
According to scientists, at the interface between genes and the environment, are factors whose roles on how nature and nurture interact at the molecular level inside our bodies influence how our genes express.
Several research data on epigenetics, has supported the thinking that taken alone, a person’s genes cannot determine if, for instance, that person ends up an optimist or a pessimist, intelligent or suffering from cancer.
There are, scientists now know, epigenetic mechanisms - molecular events governing the way the environment regulates an organism’s genome (accumulated genetic material) and their relationship to phenotype. All these influence that person’s genetic potential by regulating the extent to which his or her individual genes are expressed.
That effectively explains for example why the identical twins you might have encountered, despite possessing the same exact set of genes, have nonetheless individually grown to display subtle differences in appearance, physiology, cognition, and behavior—a group of traits that are collectively known as the phenotype (an organisms observable characteristics).
Gene Expression
Geneticists have always known that DNA, tightly wound like thread around spool to form nucleosomes - the unit of chromatin - and interacting with a host of proteins, inside a cell nucleus, requires something extra to tell it exactly which genes to transcribe.
Methyl Group (License: Public Domain): Wikimedia Commons
A methyl group, a common structural component of organic molecules is one such extra element.
Gene Expression being demonstrated in this 2007 video published by Genome British Columbia.
But how does it (methyl group) influence gene expression? First it is important to recognize that to every gene is a place, usually at the beginning of it, where proteins attach to activate the gene. What happens is that enzymes attach this carbon and hydrogen bundles (CH3)(methyl groups) to that part of the DNA.
If owing to this this, the protein can't attach due to the blocking methyl group, the gene remains unexpressed. This entire process is called methylation and because the methyl groups are attached to the genes, and reside beside but separate from the double-helix DNA code, the field was named epigenetics.
Besides methylation, there are other epigenetic processes that scientist have identified, including chromatin modification. In this, the extent to which nucleosomes are either spread or condensed is what equally determines the activity of the genes contained within the spans of DNA. Nucleosomes being relatively spread out allow genes to be expressed. Meanwhile nucleosomes being relatively condensed blocks such expression.
Influence on nature versus nurture
The question now is? How does all this influence the nature versus nurture debate?
A strong established case for nature, is that we humans are based on inherited genes from our parents. The second fact, to even out this for nurture is that our everyday life can influence epigenetic changes.
But perhaps what is most interesting, and which comes in as the common ground between nurture and nature, is the fact that some epigenetic changes have been found to be hereditary! How is that?
Epigenetic research is still at infancy, and mostly focused on the early development of organisms such as in liver cell formation verses neuron from an undifferentiated stem cell.
Recent research on development of behavior, however has established how equivalent epigenetic mechanisms indeed operate throughout in all tissues such as the brain, to drive alterations in gene expression that occur as a result of environmental challenges.
This has given way to what has now become known as behavioral epigenetics:-
Tthe study of how signals from the environment trigger molecular biological changes that effectively modify whatever happens in the brain cells
Environment in this context, alludes to everything that happens in a person’s every stage of life, including the social experiences, his or her nutrition, as well as toxicological exposures that occur to that person including prenatal in utero exposures, through postnatal to even adulthood.
In utero exposures, including a mother’s diet for example has been found to impact a fetus’s life-long feeding behavior.
1. Nutrition
Influence of diet (License: Public Domain): Wikimedia Commons
We are what we eat, that much has been proven by several studies. However when it comes to mothers, what they eat during pregnancy has been found to infer life-long effects on the genes of their children, several studies, particularly on mice, have suggested.
A 2003 mouse study conducted by Randy Jirtle, at Duke University Medical Center in Durham, North Carolina, and his colleague Robert Waterland for example successfully altered the coat color and disease susceptibility of newborn mice simply by feeding their mothers extra vitamins during pregnancy. Specifically, the mice became less prone to diabetes and obesity compared to identical mice whose mothers did not receive any vitamins supplement.
The study used Agouti Yellow mice. These are typified by possession of an extra piece of DNA in the Agouti gene, which makes them obese and Yellow in color. When however fed with Vitamin B12, folic acid, choline and betaine before, during and then after pregnancy these mother mice gave birth to pups thin and brown in color. Control mice offspring however remained obese and yellow.
Originally shared by Praveen Kulkarni, Google Plus
The addition of nutrients had effectively silenced the obese weight, yellow coat color causing Agouti gene to which had been added a methyl group (CH3). But perhaps conspicuously was the fact that the silencing of the Agouti gene by the additional nutrients occurred without altering the Agouti gene’s sequence.
Extrapolating such findings from mice to man obviously still needs a lot of data on human methylation, but some researches have already shown that lack or abundance, of food during a person’s early/formative years cause epigenetic changes that eventually lead to obesity and diabetes.
In the analogy of the identical twins, the epigenetic changes due some foods, alter how each twin’s genes are expressed so much that the difference in diet puts one twin at the risk of cancer but leaves the other unaffected.
2. Influence of mom and dad.
Parental care - A mother’s care for her young affects their responses to stress as adults.
Image Credit: Deborah Vlock
In his 1997 landmark paper published in Science, Michael Meaney and his colleagues showed that the mothering styles of mice directly influenced their pups response to stress as adults. The expression at adulthood, of stress hormones, including corticosterone were affected by Natural variations in the amount of licking and grooming prior received during infancy.
The more licking as babies, the less stress hormones as grown-ups. Accordingly, off spring of nurturing mothers inclined toward less anxiety compared to those of lackadaisical mothers. The Meaney research showed these life-long influences to be mediated through epigenetic modification at specific genes within the offspring’s brain.
In humans, early life adversity – including parental neglect – has been shown to correspond to a life-time risk of suicidal behavior. Turecki’s 2014 study published in Nature Reviews - Neurosciece, observed methylation changes in the brains of suicidal victims, alluding to a possible correlation between stressful upbringings and epigenetic change.
Frequent exposure to maltreatment by those who are meant to protect, and to provide care may signal that a person’s environment is hostile, and accordingly prompt the developing brain to adjust stress-response circuits to adapt to this hostile environment by increasing levels of alertness. A relationship between poor parent – child attachment, maladjustment in parental role and childhood abuse, and suicidal behavior has been suggested by several studies.
Overall, there is increasing evidence that epigenetic changes in the neurons are indeed responsible for several of the adult brain’s mal-adaptations to the environment..
3. From generation to generation
Grandpa's lousy childhood could influence your personality (License: Public Domain):
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Insights of Epigenetic inheritance contend that traumatic experiences in our past, or in our recent ancestors’ past, somehow leave molecular scars that adhere to our DNA.
The transmission of the effects of any such exposure of one generation to
specific environmental factors or conditions does not require that these factors/conditions be present in subsequent generations.
It is now opined that epigenetic changes besides occurring within the brain, could also occur in germ cells as a molecular trace of the experience. According to the 2014 study by Isabelle Mansuy and colleague, the cross-generational transfer of such epigenetic traces occurs through sexual reproduction as the most potent mode of transmission capable of affecting multiple generations.
Passed on to offspring, these modify the offspring’s responses to those same environmental exposures. This heritable transmission of life’s experiences to offspring without a change in the DNA sequence, Hurley, writing in his Trait vs fate article suggests could be passed down not just from parent to child, but also from this generation to the next generation.
Several studies in humans have documented inheritance of the effects of early experiences. Yehuda’s 2007 study of Parental Posttraumatic Stress Disorder as a Vulnerability Factor for Low Cortisol Trait in Offspring of Holocaust Survivors, for example established that descendants of holocaust survivors have a higher prevalence of depression and anxiety disorders.
Accordingly, the Jews whose great-grand parents were condemned to concentration camps, the Chinese whose grandparents survived the Cultural Revolution, young African immigrants whose parents survived massacres such as the Rwanda 1994 genocide, the Negro who grandparents were abused as slaves, all of these, Hurley equally alludes, carry with them more than just memories.
These experiences of our forebears, Hurley argues, are never really gone but remain a part of us, a molecular residue holding fast to our genetic scaffolding. The DNA, he contends, remains the same while behavioral and psychological tendencies are inherited.
Thus, your predisposition toward stress and depression could be a result of the neglect your grandmother suffered as a newborn.
This observation gravitates toward Jean-Baptiste Lamarck’s early 19th Century theory of inheritance of acquired characteristics, a view that has long been discredited but which, with recent developments, is now causing a bit of a stir in the largely accepted understanding of evolution..
Evidence is still scant and doesn’t entirely support Lamarck’s theory, best typified by the argument that a Giraffes neck elongated over the course of generations of reaching high up for food, however there is growing evidence that maybe Larmack had a point after all.
A study by Isabelle Mansuy and her colleagues at the University of Zurich and published in the Journal of Experimental biology, for example, subjected mouse pups to maternal separation during their first two weeks of life. The male offspring upon growing to maturity, exhibited signs of depression-like behavior.
These males, when bred with normal female mice, sired offspring showing similar depression-like behaviors as adults, despite not being subjected to stress during their upbringing. The same effects, the study observed, were equally passed onto the subsequent generation.
Implications
The burgeoning field of epigenetics investigates mechanisms that modify gene expression by mediating interactions of the environment previously assumed to be an immutable DNA blue print.
Owing to epigenetics, there is now a lot of attention being paid to the impacts of adverse conditions or factors, including but not limited to deprivation, poor parenting, among others.
A thorough understanding of DNA methylation, that epigenetic process via which genes are either turned “off” or “on”, scientists hope, will aid in the development of more effective approaches for preventing latter life conduct problems.
Being able to ‘turn off” aging, and or fine tune one’s genome is by several standards a mouthwatering prospect, scientists however are currently more interested in discovering ways for treating epigenetic diseases.
Some cancers, for example, occur as a result of the deactivation of the tumor-suppressing genes. The treatment option scientists have worked out is to develop medications that reactivate these tumor-suppressing genes. It is how the drug azacitidine works to treat leukemia. The risk of course is that, success in unblocking or blocking the right/targeted genes could also affect other genes resulting in unpredictable side effects.
Another key interest area for epigenetic studies is that of stem cells. Scientist hope that studying epigenetic changes responsible for the development of cells will eventually make it possible to dictate the tissue type that a stem cell finally develops into.
Meanwhile, epigenetics remains a burgeoning sub-discipline of biology, and is generating new insights about human development. The more we get to know about epigenetic changes, the more we shall get to understand the correlation that exists between not just our circumstances and or actions but also of our children.
It is likely that epigenetics research will override the nature –nurture debates, including the reductionist and genetically determinist perspective that currently exists on phenotype development.
Technical Explanations
Darwin’s Natural selection evolution theory suggests a slow gradual process by which organisms change with time as a result of changes in heritable physical or behavioral traits.
Freud’s Psychoanalytic theory meanwhile suggests that personality is typically established by the early age of five years. Early experiences, the theory intimates, play a big role in personality development, influencing behavior in latter adult life.
References
- Charles Darwin, "On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life," 1859, p. 162
- Moore, D. S. (2017), Behavioral epigenetics. WIREs Syst Biol Med, 9: e1333. doi:10.1002/wsbm.1333
- Robert Lamb "How Epigenetics Works" 13 October 2008.
HowStuffWorks.com. https://science.howstuffworks.com/life/genetic/epigenetics.htm 13 May 2018 - Turecki, G. (2014). The molecular bases of the suicidal brain. Nature Reviews. Neuroscience, 15(12), 802–816. http://doi.org/10.1038/nrn3839
- Waterland, R. A. & Jirtle, J. L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and Cell Biology, 23, 5293 - 5300, (2003).
- Yehuda R, Teicher MH, Seckl JR, Grossman RA, Morris A, Bierer LM. Parental Posttraumatic Stress Disorder as a Vulnerability Factor for Low Cortisol Trait in Offspring of Holocaust Survivors. Arch Gen Psychiatry. 2007;64(9):1040–1048. doi:10.1001/archpsyc.64.9.1040
- https://www.darwins-theory-of-evolution.com/
- https://www.livescience.com/474-controversy-evolution-works.html
- https://www.verywellfamily.com/overview-of-monozygotic-identical-twins-4114646
Nice work. Epigenetics is a very complex topic and you do a great job at explaining how environmental factors can affect our genomes. The Agouti Yellow mice example you give is a perfect illustration of how it can happen. The further examples showing that that epigenetic elements can be genetically inherited are really cool and actually show that Lamarckian inheritance can occur which is amazing.
Keep up the good work.
Thanks @tking77798 for the high commendation, and for reading.
I am glad you think i managed to write this out just fine, despite the complicated subject i handed.
The challenge in writing on such subjects is to simplify the complication, without making trifling it so much. Just know it took me a couple of day, but i am glad it proved worthwhile.
I congratulate you, @mirrors, for a well researched and well written essay! Thanks for sharing, and keep up the good work! :-)
Thanks @zyx066. It took me a couple of days, but i am glad it proved worthwhile.
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Hey, great work. It clearly seems that you put a lot of effort on writing this. Genetical topics can be hard to explain sometimes, but you did it well and most important: easy to understand for everyone.
The challenge with such topics is always to strike a proper balance, to simplify the complicated without trifling the subject too much.
I am glad you think i managed this.
Just know it took me a couple of days to pen it down, but i am glad it proved worthwhile.
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