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Epigenetics is the study of the processes that underlie developmental plasticity and canalization and that bring about persistent developmental effects in both prokaryotes and eukaryotes. In my research, I came across a rather difficult yet slight interesting article entitled, “How might epigenetics contribute to ecological speciation?” Ecological speciation involves the formation of a new species in the course of evolution with one’s physical surrounding. It interplays with adaption to different environments and the concurrent incompatibility of reproductive isolation. Epigenetics is viewed as a process that does not interrupt the DNA in organisms. It can be an induced processed based from generation to generation through germ line cells or somatic cells. However, in embryonic development epigenetics changes its course. In the formation of a zygote, DNA methylation can occur as a biochemical process. Most epigenetics witnessed in this article pertain to DNA methylation and phenotypic plasticity. Of course, phenotypic plasticity is in more correlation to fish or the Drosophila in this research more so than humans. In this piece, Smith and Ritchie describe phenotypic plasticity as often allowing organisms to respond adaptively to environmental factors. Adaptation to a range of new environments may follow a single invasion event, for example when fish invade glacial or other new lakes, or occur with on-going gene flow or fluctuating environments.

One interesting and understandable method mentioned in this article was the criticisms of epigenetic marks in evolution. There we three main factors that contribute to the controversy. First, epigenetic variation is not seen as a primary driver of evolution in the same way as mutations. I personally cannot disagree or agree with this critique, because a mutation is usually witnessed with a disruption of DNA in humans, not necessarily the external environment; however, I cannot speak for all other organisms. Secondly, an important aspect of Neo-Darwinism is that evolution is not “directed”, since it can be induced and stably inherited, it can then be seen as directed. Thirdly, epigenetic marks are seen as dependent on DNA and thus do not evolve independently of genetic variations. Now, this I can partially agree. I realize in this article as well as the required reading by Jalon and Razz that RNA was mentioned throughout in regards to prions, rRNA, and DNA methylation. I couldn’t see how RNA could be discussed without the use of DNA since they are partners in regards to translation and transcription. Later however, I did realize epigenetics transformation from generation to generation with induction and allopolyploidization. In all, one’s environment can result in adaptability among organisms without altering their DNA obviously. Now, do I agree completely is a different question.



The Author of this chapter, William R. Leonard, is currently a professor of anthropology at Northwestern University. He holds the title at this university as the Abraham Harris Professor of Anthropology. He He received his PhD from the University of Michigan in 1987. His research interests include biological anthropology, adaptability, growth and development, and nutrition focusing on populations in South America, Asia, and the United States. His most recent publication was on the topic of precursors to over-nutrition and the effects of household market food expenditures on body composition among the Tsimane in Bolivia.

The ecological variation of available food has been an important factor throughout the history of human evolution and continues to shape the biology of traditional human populations today. The relationship that humans share with their environments (i.e., acquisition and expenditure of energy) has adaptive consequences for both survival and reproduction. Humans are similar to other primates in that we are omnivorous (i.e., we eat both plants and animals) and we have nutritional requirements (e.g., the inability to synthesize vitamin C) that has caused us to adapt diets that include large quantities of fruit and vegetable material. However, what is unique to humans is our highly diverse diet (i.e., dietary plasticity) that evolved because of cultural and technological innovations that developed for processing various resources. This has allowed humans to expand into the many different ecosystems that we inhabit today.


In order tomaintain our health, humans require six classes of nutrients:

(1)   Carbohydrates are the largest source of dietary energy for most human groups. For example, carbs account for about 40-50% of the daily calories of U.S. adults. There are three type of carbohydrates including monosaccharides (i.e., simple sugars), disaccharides (i.e., sugars formed by two monosaccharides), and polysaccharides (i.e., complex sugars made up of three or more monosaccharides).

(2)   Fats are the most calorically dense source of dietary energy and provide the largest store of potential energy for the body to do biological work. Fats are divided into three groups. The first, simple fats, is mostly made up of triglycerides (i.e., glycerol and fatty acid). Fatty acids can be further divided into saturated (i.e., found in animal products) and unsaturated fats (i.e., monounsaturated and polyunsaturated mostly found in vegetable oil). Compound fats are the second type of fat that consist of a simple fat in combination with another type of chemical compound, such as a sugar or a protein. Compound fats are important for blood clotting and insulating nerve fibers. The third category of fats is known as derived fats, which are a combination of simple and compound fats (e.g., cholesterol). Cholesterol is important for normal development and function. It is also a precursor in the synthesis of vitamin D and hormones like estradiol, progesterone, and testosterone.

(3)   Proteins are an important energy source, but they are also crucial for the growth and replacement of living tissues. In order to get theadequate nutrition per day a person needs a sufficient quantity and quality of protein. The digestibility and amino acid composition determine the quality of a protein. Complete proteins have the necessary amino acids in the quantity and proportions that are needed to maintain healthy tissue repair and growth. Good sources of complete proteins come from animal foods including eggs, milk, meat, fish, and poultry. Incomplete proteins are those that lack one or more essential amino acids. Incomplete proteins are found inplant foods, such as grains, legumes, seeds, and nuts. So if you want to be a vegetarian it will require combining different sources of plant foods in order to get all of the essential amino acids you need.

(4)   Vitamins are not a source of energy, because they just help the body use energy and carry out other metabolic activities. There are two categories of vitamins: water-soluble vitamins (i.e., B vitamins and vitamins C are needed on a daily basis because they are not stored in the body) and fat-soluble vitamins (i.e., vitamins A, D, E, and K are stored in the body so they don’t have to be taken every day). Be careful because if you take too many fat-soluble vitamins over a long period of time it can be toxic.

(5)   Minerals, such as iron, are inorganic elements that are needed in many biological molecules (e.g., hemoglobin) and are vital formaintaining various physiological functions.  

(6)   Water makes up a large portion of our body weight at 40-60% for adults. Humans get water from liquid intake, food, and “metabolic water” that is produced as the result of energy-yielding reactions.


Recent research has focused on developing and refining energy and nutrient requirements for the various human populations around the world. Many factors must be considered in order to efficiently estimate a person’s daily energy needs including diet, daily activities and exercise, energy costs for reproduction, sex and age. According to the World Health Organization (WHO), women who are pregnant need an extra 85 kcal/day during the first trimester, an extra 285 kcal/day during the second trimester, and an extra 475 kcal/day during the final trimester. Children’s and adolescents’ energy requirements are measured differently from adults, because they have extra energy costs that are associated with growth. Pregnant women, children and adolescents also require more protein than the average adult.

The dietary patterns and metabolism of humans has been shaped by the energy demands of our relatively large brain. The energy demands of humans are usually divided into maintenance energy (i.e., needed for day-to-day survival) and productive energy (i.e., needed for growth and reproduction). Humans spend a larger portion of their daily energy budget on brain metabolism when compared to other organs in the body. We use 20-25% of our BMR (basal metabolic rate) on brain metabolism compared to the 8-10% used by primates and only 3-5% used by other mammals. It has been hypothesized that because of the high metabolic costs of our brains we require high-quality diets. Animal foods contribute to about 45-65% of the diet amonghunter-gatherers, which is much higher quality than expected for primates of our body size. Humans also have small gut volumes for our size, because most large-bodiedprimates have large intestines for digesting fibrous, low-quality diets. So, we probably evolved to have smaller intestines and a reduced colon because of our high-quality diets.  


Throughout the evolution of the different hominin species there has been changes in brain and body size. The australopithecines had smaller brains relative to their body size, but with the emergence of the genus Homo there was a dramatic increase in brain size. The body size of Homo erectusalso increased, but the changes of the brain size were much larger than those that occurred with body mass. Homo erectus had a larger brain and body but smaller teeth, which suggests that this species relied on a different subsistence source than the australopithecines that was probably easier to digest (i.e., less fibrous plant foods) and richer in calories. The greater nutritional stability of the genus Homo provided the fuel for the energy demands of their larger brains.   

While Humans do have a diverse range of diets across the world, environmental pressures have contributed to adaptations such as lactose tolerance and the ability to digest starch. Some adaptations have become maladaptive in modern society, such as increased fat storage, which has lead to increasing rates of obesity. The amount of animal foods (meat, eggs, milk, etc.) varies across cultures and geographic location. Contemporary foraging groups consume animal foods for approximately 45-65% of their diets. However in the US our animal foods consumption is approximately 26% of our diet. Macronutrient consumption also varies across populations. Americans derive 15% from protein, 34% from fat, and a very high 51% of their energy from carbohydrates. This carbohydrate % is higher than every other population except for small-scale farmers. Another interesting statistic is the estimated consumption percentages estimated for modern foragers: 20-31% protein, 38-49% fat, and 31% carbohydrates. What do you think about these forager percentage estimates in comparison to American percentages?  


Carbohydrates consumed in subsistence-level societies are typically more complex with a small percentage of their carb consumption coming from simple carbs. American carbohydrates however come mostly from simple carbs and processed grains. These simple and processed carbs are absorbed faster into the blood stream than more complex varieties. A high glycemic level in the blood stream may lead to insulin resistance, which may lead to obesity, type II diabetes, hypertension, hyperlipidemia, and coronary heart disease. In comparison to subsistence-level populations, industrialized men weigh approximately 26.5 lbs more and require 150-200 kcal less. Industrialized women weigh 17.7 lbs more and demand approximately 90kcals. The US Department of Health and Human Services has also released guidelines that adults do approximately 150min/week of moderate physical activity. Another recommendation by IOM set the bar higher at 1 hour/day.

Another interesting fact from later on in the chapter is associated with the enzyme amylase. Carbohydrate digestionbeings in the mouth with amylase (enzyme found in saliva). Populations with high-carb diets have more copies of the AMY1 gene and therefore more amylase. So differences in dietin recent human evolution have exerted strong selection at the AMY1 locus. Also humans have three times as many AMY1 genes as chimps and bonobos. This implies that there was strong evolutionary selection on this gene during the early divergence of hominins from apes.

Food processing techniques are developed to fit the needs of the subsistence-level society that grows that particular crop. Corn, a major crop in the Americas, is high in protein but low in the amino acids lysine and tryptophan as well as the B vitamin niacin. To solve this problem, corn is processed in the presence of alkaliproducts (e.g., ash, lime, and lye) adding back these key nutrients. Andean populations processed potatoes in a way that removes the hazardous glycoalkaloids. Also, Asian populations processed the antitrypsin factor out of soybeans.

Climate may also have an effect on metabolic rates. Studies show that populations living in warmer climates have a lower metabolic rate than those living in colder environments. This attributes to a variation in dietary needs in different climates. It is being questioned whether these population differences are genetic or part of acclimatization.


The ability to digest lactase disappears after weaning for most mammals, however some human populations have developed the ability to digest lactose and are thus lactose-tolerant. This change is a relatively recent evolutionary event occurring within the last 10,000 years. Genetic analysis shows that selection for the lactase persistence appeared about 7500 years ago. The allele spread across Europe in association with dairy/farming subsistence. It also appears to have evolved independently in some African populations approximately 6000-7000 years ago. However, some malabsorbers (genetically intolerant) people are able to digest lactose, and some genetically tolerant people are unable to digest milk. This suggests that dietary habits during development may contribute to lactose tolerance. In the malabsorbers this is due to an increased tolerance in the colon instead of an increase in lactase (enzyme that digests lactose. Life tip:If it ends in –ase it is an enzyme).

African-Americans have an increased risk of cardiovascular diseases. One model says that the problem is a consequence of genetic adaptation for efficient sodium (Na+) storage. Na+ is readily lost in sweat and was rare in many tropical societies. These groups have lower sweat rates and lower sodium concentrations in their sweat than European control groups. Now with salt being readily available to people who have genetically evolved to retain it, these people have higher bloodpressure. In relation to this model, the same scientist says that slaves brought over on slave ships would have been exposed to severe dehydration, and those with salt-retention would have been more likely to survive. So dependents of slaves have a high probability of having this recently selected for trait. (This study focuses on the West Indies and thereforemay not be representative of the US). Some argue that the slavery hypothesis is overly simplistic and a modern representation of racism in science. Still others argue that this increased risk is related to socioeconomic stress. Increased stress leads to increasedsympathic nervous system activity. The release of norepinephrine and adrenocorticotropic hormone elevate blood pressure by increasing sodium retention.  Do you think the slavery hypothesis is racist? Which of these models makes more sense to you?


Type 2 diabetes is when your cells reduce the number of insulin receptors and then become insensitive to insulin (your insulin levels are not necessarily affected). “Thrifty Genotype” is the current hypothesis for why we evolved to be sensitive to insulin. Hunter gather societies were faced with seasonal and year-to-year fluctuations in availability of nutrients and therefore would have developed a “thrifty genotype” that would have allowed for a quick release of insulin and an increase in glucose storage during times of plenty. Nowadays we live in a constant state of plenty, and this “thrifty genotype” is now maladaptive and a contributor to diabetes and obesity. Native Americans have a very high rate of diabetes which could beassociated with the fact that they were part of a population with many “thrifty genotype” traits due to their old lifestyle, and due to the recent change in diet they are especially at risk. In addition to the ancestry view of “thrifty genotype”, recent studies also show that babies with poor nutritional conditions in early life select for “thrifty phenotype” which can also lead to increased rates of diabetes and obesity in adulthood. Could thrifty phenotype be epigenetic and passed on to offspring?


The obesity epidemic is a combination of all the above traits, and is associated with the transition from subsistence-level nutrition to modern-day industrial nutrition styles (processed foods, growth hormones, etc.). Thrifty genotype and phenotype are playing a huge role in populationsthat are just now gaining access to stable food supplies. Urbanization and rising incomes throughout the developing world have increased rates of overweight and obesity. Trends in US food use patterns the global trends. Energy consumed from soft drinks has increased 70% since the mid-1970’s. Available energy from vegetable oils has increased by 30% over that same time period. Other factors include the increase in eating away from home and snacking. Sugars, processed grains, and added fats are some of the cheapest food options, and with today’s bad economy poorer people are consuming more of these bad nutrients. Our modern environment has been characterized as “obseogenic”—that is, providing abundant food energy, while requiring little work or activity to produce that energy. What do you think about the obesity epidemic? Is genetics an excuse?





About the Authors

Zaneta M. Thayer is a biological anthropologist pursuing her doctorate at Northwestern University, and she has a B.A. in anthropology and biology from Dartmouth College. Thayer is interested in how the environment affects patterns of human biological variation, particularly during early development. Her primary research has been on the epigenetic effects seen in fetal development. One of her long term goals is to unite developmental biology with the Modern Synthesis as an expansion of modern evolutionary theory.

Chris Kuzawa, a Professor  at Northwestern University, is a biological anthropologist with a background in epidemiology. He received both his PhD and his MsPH (Masters of Science in Public Health) from Emory in 2001.  He focuses on developmental biology and the diseases and effects that early postnatal environments have on humans. The premise of this research is that what a mother eats during pregnancy, her access to adequate prenatal care, or her stress level, may permanently alter offspring biology in a fashion that influences risk for the most common causes of adult morbidity and mortality, including hypertension, diabetes, and heart attacks. He focuses on the term "Developmental Plasticity", which is the sensitivity of a developing body to its environment.

His current projects are on developmental influences on obesity and male reproductive ecology in the Philippines and Inter-generational influences on health in the United States

Biological memories of past environments: Epigenetic Pathways to health disparities

This article was rather interesting as it similar to the discussion we had in class on Tuesday on the lead affecting children. Following are just some summed points from each section of the paper.


  • The introduction spoke about  current and recent research that environmental exposures can influence biology and health, which is epigenetics.
  • Although that has been studied, the linkage between environmental factors and patterns of disease through epigenetics processes.
  • Previous research has seen a deleterious health impacts of economic and status inequality, such as stress or discrimination. And that being of low social status increases disease risk.
  • Although these linkages are understood, the biology behind them isn't totally clear.
  • Studies like these are important from a public health perspective as they can help to understand where certain diseases are coming from.

Nutritional Stress

  • Nutritional status can influence epigenetic profiles.
  • Several studies have show than nutritional exposure during critical periods can significantly affect the life course of an individual. For instance a low protein maternal diet in rats led to increased risk of type 2 diabetes.
  • Nutritional epigenetic effects may extend into successive generations  through germ lines.  Food shortage in a generation may increase the grandchild's mortality risk from cardiovascular diseases.
  • Food security and access to food supplies affects functional outcomes in offspring.

Psychosocial Stress

  • Traditional studies of stress and health tend to involve blood pressure or hormone metabolism, but new research is trying to link psychosocial stress and epigenetically-based changes in gene regulation.
  • Data has shown that stress related epigenetic changes can be passed on to offspring, as with the stressed out rats, passing on their epigenetic profiles to their children.
  • Stress can also be varied in humans based on socio-economic status and other factors such as perceived discrimination. Differing levels of stress can cause certain groups to be at risk for different diseases and affects.

Environmental Toxicants

  • It is well known that toxic chemicals and materials can affect epigenetic markers and change gene expression. Heavy metals in particular have been seen to affect methylation (an important biological process whereby a methyl group is added to another biological compound) and serotonin production.
  • Exposure during pregnancy can modify genes and lead to eventual development of diseases down the road.
  • Certain chemical exposure can even affect several generations, as mice treated with an endocrine disruptor were seen to affected negatively sperm for several generations. This shows the long lasting effects of certain toxicants.

Future Directions

  • To get a better idea of what areas and groups to study we have to look at the underlying social structure.
  • Studies need to be conducted on the potential to change epigenetic linked diseases, not just conducted to identify them.
  • This knowledge of epigenetics needs to be brought to the public's attention and to the policy makers in an attempt to show how important environmental factors are on developing bodies.

Food for Thought

  • Are there other ill health effects that could potentially be linked to early epigenetic factors besides those mentioned in the article?
  • Can any other diseases previous attributed to other things, such as stress actually be epigenetic in origin?


Epigenetic Mechanisms, Quick &  Dirty

Jablonka & Raz (2009) show us this elegant illustration of broad and narrow epigenetic transmission.

Epigenetic inheritance in the broad sense is the inheritance of developmental variations that do not stem from differences in the sequence of DNA...information transference that can take place through developmental interactions between mother and offspring..., through social learning..., and through symbolic communication.

We...define cellular epigenetic inheritance as the transmission from mother cell to daughter cell of variations that are not the result of differences in DNA base sequence and/or the present environment.  Transmission can be through chromatin marks, through RNAs, through self-reconstructing three-dimensional structures, and through self-sustaining metabolic loops.

In the single-cell "bottleneck" variety of epigenetic inheritance (pathway a in the above diagram) Jablonka &  Raz focus on...

The environment may induce epigenetic variation by directly affecting the germline or by affecting germ cells through the mediation of the soma, but, in either case, subsequent transmission is through the germline.

Evolutionary Implications

According to Jablonka & Raz (2009), there are 5 effects of epigenetic mechanisms & inheritance vis-a-vis evolution:

(i) evolutionary change occurring through selection of epigenetic variants, without involvement of genetic variation; (ii) evolutionary change in which an initial epigenetic modification guides the selection of correlated genetic variations; (iii) evolutionary change stemming from the direct effects of epigenetic variations and epigenetic control mechanisms on the generation of local and systemic epigenomic variations; (iv) evolutionary change resulting from the constraints and affordances that epigenetic inheritance imposes on development; and (v) evolutionary change that leads to new modes of epigenetic inheritance.

Siberian Silver Fox Experiments

The Siberian silver fox experiments are so cool, & often cite them as an example of gene linkage.  Honestly, I was just BSing in suggesting that the curly tails, rounded nose, etc. were possibly linked on the same chromosome to tameness & recognized that there might be other factors involved.  Lo & behold, a citation in Jablonka & Raz (2009) pointed us toward epigenetic studies to come out of that body of research.

Cute & cuddly silver foxes
Cute & cuddly silver foxes

It turns out that the coat spotting & non-spotting variation that we associate with domestication occurs too quickly to be pure mutation, though it behaves like a dominant & semi-dominant trait, & couldn't be explained by inbreeding because the inbreeding coefficient was too low (0.03).  Instead, they believe

the stress of domestication and selection for tameness targeted genes with large effects in the neuro-hormonal system...and may have heritably reactivated some of them...This epigenetic interpretation, in terms of new epimutations rather than new mutations, explains the high rate of appearance and disappearance of some phenotypes, and support for this comes from the fact that at least two of the genes (Agouti and C-kit) that seem to be involved in the changes are known to have heritable epigenetic variants in mice...

One aspect of epigenetics that seems important here is the concept of canalization, introduced by Waddington several decades back (he also introduced the concept of epigenetics in general, which everyone rightly thought was Lamarkian & wrongly ignored--turns out he was on the money).  Roughly, canalization means that some environmental perturbation pushes a phenotype into a canal or valley, whereafter selection pressures prevent the phenotype from returning to its previous state because the "climb" up the sides of the canal or out of the valley are too steep.  Think of a marble on a tabletop that is essentially flat but has a valley to one side of it.  Stochastic chance dictates that the marble can roll any which way, but if it happens to roll toward the valley, it gets stuck there & can only roll further in the valley.  Or as this image illustrates, there are several possible environmental variations possible, but once a phenotype goes one way (plastically), it cannot go back.

So it seems to be with the silver foxes.  Once an environmental condition pushes silver foxes (or wolves before them) one way (luring tame ones to their yummy debris & handouts) or another (spooking the nervous ones to run away), a cascade of epigenetic mechanisms pushes them further along.  At that point, according to this model, tame ones cannot become anxious/aggressive & vice versa.

While cute silver foxes that you can cuddle with get all the press, the less publicized but equally fascinating is the aggressive foxes that want to rip your face off.

Aggressive domesticated silver fox Courtesy of Lyudmila Trut / Institute of Cytology andGenetics / The Siberian Division of the Russian Academy of Sciences (Source: Dugatkin 2003,
Aggressive domesticated silver fox Courtesy of Lyudmila Trut / Institute of Cytology andGenetics / The Siberian Division of the Russian Academy of Sciences (Source: Dugatkin 2003,

So what's going on with these aggressive foxes?  According to Popova (2006), there are at least 16 genes that influence aggression, but most aggression behavior is influenced by just a few of those.  A major player seems to be serotonin (5-HT).  The 5-HT pathway in the brain suppresses aggression.  5-HT is not a gene though, it is a hormone; & genes code for proteins.  So if there's a gene change, what is/are the gene(s)?  It could be any gene that produces an enzyme involved in the essential mechanisms of the 5-HT system, which include synthesis/degradation, reuptake in the synaptic cleft, & density/sensitivity of receptors (for more background on 5-HT, I've written on this before here).  As the figure below illustrates, there are enzymes that catalyze serotonin synthesis (TPH & decarboxylase of aromatic l-amino acids), two enzymes that help break serotonin down (MAO A & B), & an enzyme (SERT) that transports serotonin.

There are two TPH genes, & it is the 2nd one (TPH2), expressed in the brain & responsible for the central nervous system, that effects 5-HT & seems to be responsible for aggressive behavior.

Silver foxes displaying friendly responses to human contact were shown to have higher 5-HT and 5-HIAA levels, and higher TPH activity in the midbrain and hypothalamus in comparison to nonselected wild-type silver foxes bred in captivity. Importantly, the changes were found in the midbrain representing the area of main location of TPH2-synthesizing cell bodies.  These findings were interpreted as an indication of an increased activity of the brain 5-HT system in the tame animals and, subsequently, a decreased activity of this system in highly aggressive animals.

MAO A has a higher affinity for 5-HT & is considered the principle enzyme in breaking down serotonin.  When MAO A is disrupted in mice, they get more aggressive.  Deletion of SERT (the transporter that allows 5-HT molecules not taken up by post-synaptic receptors to be recycled & reused) in knockout mice also produces aggressive behavior.  Finally, there are 14 different subtypes of 5-HT post-synaptic receptors.  Genetically low aggression has been associated with increased expression of specific subtypes of these receptors in the midbrain & specific densities & function in specific regions of the brain.  These likely function to suppress aggressive behavior.

The figure below depicts this as essentially two pathways, which we can compare analogously to the Jablonka & Raz depiction of the narrow "bottleneck" pathway, albeit via two cells (or genes).  I think.

If any one of these mechanisms or either of these pathways influences aggression, they will interact with the environment to mutually reinforce themselves & push the marble down toward the other pathway too.  In other words, if the stress of domestication bumped the marble off the plane, having even only a slightly higher tendency of aggression relative to tameness will result in amplification of the entire aggression pathway, even if the environmental conditions of captivity are thereafter removed (i.e., the animal is released).  What still remains to be clarified is how the initial brain changes occur & the roles of other mechanisms in the system.

Zane Thayer & Chris Kuzawa review data that offer a clue.  They point out that "psychosocial stress contributes to the social gradient in health" (2011:799).  This is well-established by now, but the mechanisms are interesting.  In two studies particularly relevant to our question of how the stress of domestication may influence aggression in silver foxes, childhood abuse was associated w/ methylation differences at the GR (glucocorticoid) locus in the hippocampus & the serotonin transporter protein (SLC6A4) locus.  Another study found that maternal depression during pregnancy predicted stress reactivity & methylation of the GR locus in buccal cells of their infants 3 months after birth.  Methylation is the addition of a methyl group to a substrate or substitution of an atom by a methyl group.  This can take place in DNA or proteins.  In DNA, it can result in the change of an amino acid base, thus a change in the genetic code resulting in production of different or altered proteins.  In proteins, it results in regulatory changes in the protein functions, so methylation can have wide-ranging effects.  The methylation of the GR receptor locus may affect things like the binding of glucocorticoids to the receptor.  Glucocorticoids are best known for their role in stress response, but, relevant to this discussion, they are also operative in memory consolidation and learning, as contextual fear conditioning, among many other functions.  The SLC6A4 serotonin transporter protein terminates action of serotonin in the synapse & recycles it, which is a key function in mood stabilization.  Low serotonin is associated with high fear response.

So the psychosocial stress of domestication in some silver foxes could result in methylation of glucocorticoid & serotonin receptors, directly influences fear/aggression response in pups, that persists throughout their lives.  It can also influence depression in mothers that is passed on in the receptor activity of their pups.  We can link this with Larry Schell's model of risk-focusing.  Replace "SES" with "personality."  Fear/aggression in mothers increases the risk for fear/aggression in descendants, as tameness in mothers increases the risk of tameness in descendants.

Larry Schell's risk-focusing modelAlthough the model above suggests gene line changes, the broad epigenetic view suggests that some of these influences may not influence the germ yet still persist over multiple generations because of the influence that maternal disposition has on offspring gene expression.  Or, as Thayer & Kuzawa note

...Genes are regulated by biological "memories" of experiences acquired earlier in our own lives, and even by recent predecessors... (2011:801)


Mechanisms of Cellular Epigenetic Inheritance

Epigenetic inheritance is basically the observation that offspring may inherit altered traits due to its parents past experiences. So a parents experiences, in the form of epigenetic tags, can be passed down to future generations. Epigenetic inheritance systems are  the processes and mechanisms that underlie cellular inheritance.  There are four types of EISs recognized today and they are....

  1. EIS based on self sustaining regulatory loops
  2. EIS based on three-dimensional templating
  3. Chromatin marking EIS
  4. RNA mediated EIS

All of these can contribute to between-generation epigenetic inheritance.

SELF SUSTAINING LOOPS: These are metabolic circuits through which different patterns of activity can be maintained resulting in alternative heritable phenotypes. The early studies of the loops involved the bistability of the lac operon of Escherchia coli and this system has been analyzed at molecular and theoretical levels. The studies showed that when inducer concentrations are low, genetically identical cells can generate two alternative, true breeding, stable phenotypes. These loops have been described in bacteria and other taxa.

Three-Dimensional Templating: Structural inheritance refers to the inheritance of alternative three dimensional structures through spatial templating: a variant 3-D structure in a mother cell guides the formation of a similar structure for a daughter cell, leading to the transmission of the architectural variant. - This all started from the investigation of cortical variations in ciliates. A modified organization of the cilia on Paramecium can be inherited through many asexual and sexual generations. Another form of this structural inheritance is the propagation of prions. A single protein can misfold into several different conformations that have specific growth dynamics, stabilities, pathologies, and cross species infectivity. Many prions can interact which could lead to the formation of different transmissible phenotypes. SO unicellular organisms which have the same genotype and live in the same enviroment can exhibit heritably different morphologies and physiologies.

CHROMATIN MARKING EIS:  Chromatin is what is inside chromosomes and includes DNA and everything in it. The organization and location of chromatin and chromosomes determine everything concerning how genes are transcribed, how DNA repair works, how different chromosomal domains are organized, and how chromosomes behave during the cell cycle. There is evidence that chromatin variations can be transmitted through generations of people. Therefor the study of the chromatin marking EIS is crucial for the understanding of development and heredity.

RNA MEDIATED EIS: RNA is central to the regulation of cellular dynamics in the eukaryotes and is also involved in cell and organism heredity. RNA interference has been located in all eukaryote phyla from yeast to man. In RNA pathways, double stranded RNA molecules are chopped into shorter dsRNAs by the enzyme dicer. The resulting siRNA is loaded onto a complex of proteins, one strand of the duplex is removed and the other directs silencing. RNA can affect cell and organism heredity in several different ways, one example being the result of replication of siRNA through RNA dependent RNA polymerase.