The Developing Genome: An Introduction to Behavioral Epigenetics

by David S. Moore

Why do we grow up to look, act, and feel as we do? Through most of the twentieth century, scientists and laypeople answered this question by referring to two factors our experiences and our genes. But recent discoveries about how genes work have revealed a new way to understand the developmental origins of our characteristics. These discoveries have emerged from the new science of behavioral epigenetics--and just as the whole world has now heard of DNA, "epigenetics" will be a household word in the near future.

Behavioral epigenetics is important because it explains how our experiences get under our skin and influence the activity of our genes. Because of breakthroughs in this field, we now know that the genes we're born with don't determine if we'll end up easily stressed, likely to fall ill with cancer, or possessed of a powerful intellect. Instead, what matters is what our genes do . And because research in behavioral epigenetics has shown that our experiences influence how our genes function, this work has changed how scientists think about nature, nurture, and human development. Diets, environmental toxins, parenting styles, and other environmental factors all influence genetic activity through epigenetic mechanisms; this discovery has the potential to alter how doctors treat diseases, and to change how mental health professionals treat conditions from schizophrenia to post-traumatic stress disorder. These advances could also force a reworking of the theory of evolution that dominated twentieth-century biology, and even change how we think about human nature itself.

In spite of the importance of this research, behavioral epigenetics is still relatively unknown to non-biologists. The Developing Genome is an introduction to this exciting new discipline; it will allow readers without a background in biology to learn about this work and its revolutionary implications.

Genres: Science, Biology, Nonfiction, Genetics, Psychology, Neuroscience, Health

312 pages, Kindle Edition

First published January 6, 2015

About the author

David S. Moore is a Professor of Psychology at Pitzer College and Claremont Graduate University in Southern California. He received his B.A. in psychology from Tufts University and his M.A. and Ph.D. in developmental and biological psychology from Harvard University; he also completed a postdoctoral fellowship at the City University of New York. He is a developmental cognitive neuroscientist with expertise in perceptual and cognitive development in infancy. His empirical research has produced publications on infants' reactions to infant-directed speech, on the development of spatial cognition, and on infants' rudimentary perception of numerical quantities. His theoretical writings have explored the contributions of genetic, environmental, and epigenetic factors to human development. His first book, The Dependent Gene (2001), was widely adopted for use in undergraduate education, was translated into Japanese, and was nominated for the Cognitive Development Society's Best Authored Volume award. His new book on behavioral epigenetics, The Developing Genome, was published by Oxford University Press in 2015.

Reviews

[Bill Leach · Rating 3 out of 5]

1 - Context

It is not nature versus nuture, but nature and nuture.

2 - Phenotypes

"Epigenetics refers to how genetic material is activated or deactivated - that is, expressed - in different contexts or situations." "... people's genomes effectively change as they live out their lives." "We are born with a developing genome, one that changes in response to its environmental context." The discovery of epigenetic inheritance will force a rethinking of the neo-Darwinian synthesis, which holds that acquired traits cannot be inherited.

3 - Development

As an organism develops, the cells differentiate to form various body parts. Conrad Waddington included cellular differentiation in the field of epigenetics. Definitions of epigenetics vary from as wide as how genes are regulated by their environments (including neighboring cells), to the narrower study of how heritable changes in gene function that do not involve changes in the DNA sequence. The author uses the wider definition which includes the effects of the local environment through the life of the organism.

4 - DNA

"Classical" molecular genes present in DNA encoding proteins which perform specific functions in our bodies. The author mentions uncertainty in what a gene is, claiming that for contemporary biologists "... the gene remains a fundamentally hypothetical concept to this day." This seems to be inexact as it appears that what is happening is that the definition of the gene is being refined to recognize that the regulation region may be separated from the coding region.

5 - Zooming in on DNA

Genes are present in DNA as series of nucleotide base triplets, each of which codes for an amino acid, which together form a protein. Parts of the non-coding DNA contain regulating regions that control the expression of the encoding genes. Also present is non-coding RNA which is not used to create proteins, but has a regulation role.

Introns are sequences within coding genes that are spliced out after transcription to form the final RNA sequences used for creating the proteins. However, alternate splicings can occur due to RNA regulation such that individuals may differ in the proteins produced by the same gene.

6 - Regulation

Only one third of the material in a chromosome is DNA. Another major component are the histones, around which segments of DNA are wound, which control access to the DNA and therefore its expression. DNA methylation occurs when a methyl group attaches to a DNA strand and usually results in deactivation of a gene. Methylation of a histone can activate or deactivate DNA depending on other factors. Histone acetylation usually activates a section of DNA. A variety of microRNAs and other proteins can also mediate gene expression. It is not clear whether gene activation / deactivation is binary or whether partial regulation can control the rate of protein production. Some types of regulation such as DNA methylation tend to be long term, perhaps across an organism's entire life, while other mechanisms are more dynamic. At any given time, an individual posses not only a genetic code in its DNA, but also an epigenetic code in its epigenome.

7 - Zooming in on Regulation

Some sequences of DNA are imprinted depending upon whether they originate with the father or the mother, silencing their expression. Prader-Willi syndrome occurs when a certain segment on the paternal 15th chromosome is defective, as the same sequence on the maternal chromosome is deactivated due to imprinting. Angelman syndrome is opposite, resulting from a defective (different) sequence on the maternal 15th chromosome where the same sequence on the paternal chromosome is deactivated due to imprinting.

X-inactivation occurs in females. They inherit X chromosomes from both the father and mother, one of which is almost completely turned off early in the development of the embryo. Either the paternal or the maternal X chromosome may be active in any given female. Calico cats are a result of the pigment gene being on the X chromosome. If a cat inherits maternal and paternal genes for different colors, random inactivation will result in the patchy color scheme.

8 - Epigenetics

Studies show that identical (monozygotic) twins who have the same genome, differ in their epigenomes. Floral peloric mutations are often due to epigenetic variation - methylation of the Lcyc gene which controls dorsoventral asymmetry. Honeybee queens are genetically identical to their sister workers, but are formed when they are fed royal jelly which in some way de-methylates genes that are normally inactive.

Circadian rhythms are controlled by the hypothalamus which varies the rate of production of various proteins through the daily cycle. The protein production is varied by turning certain genes on and off through methylation and acetylation of their associated histones.

9 - Zooming in on Epigenetics

Any given gene can be controlled by a variety of regulatory sites that bind to a variety of different transcription factors. Conversely, a single transcription factor can become attached to a number of regulatory sites, controlling a variety of genes.

The histones are arranged as four pairs, each of which is different. Each has a tail that may have a variety of amino acids, each of which (or a combination) may be acetylated causing activation of the gene. A family of proteins, the histone acetyl-transferases (HATs) carry out acetylation in an orderly fashion. The HDACs reverse the process.

DNA methylation occurs when a methyl group is attached to a cytosine base, creating an "mC" base. DNA methylation is more stable than the regulation through the histones and it is thought the process may be important for maintaining already silenced genes. mC bases may be further modified to hydroxymethylcytosine (hmC), this base being found in high concentrations in neurons and embryonic stem cells. Th hmC base may be a marker for subsequent demethylation.

10 - Experience

Maternal care influences the character of offspring, and in rats it has been shown that licking and grooming (LG) makes the offspring better able to handle stress. Low levels of LG allows more methylation of genes producing the stress-moderating protein GR.

11 - Zooming in on Experience

The body responds to stress by producing adrenaline which stimulates the production of cortisol. The cortisol prepares the body for action in ways including increasing blood sugar for energy production, but it also suppresses the immune system. Glucocorticoid receptors (GRs) allow recovery from stress by detecting the presence of cortisol and reducing the expression of genes that produce the cortisol.

Research has shown that low levels of LG causes more DNA methylation of the genes producing the GRs, making the offspring less able to recover from stress. Moreover, their immune system is weakened.

12 - Primates

Studies in rats, monkeys and humans (suicide victims) correlate stress, particularly in early life with DNA methylation. While such changes can be seen in the DNA of blood cells, many more are seen in brain cells. Early life stress may be greater in certain socio-economic or racial groups, causing differing disease profiles - it is suggested that this may be the cause of the disparity in cardiovascular disease between white and black Americans. The Human Epigenome Project aims to identify, catalog and interpret DNA methylation patterns of human genes in all major tissues.

13 - Memory

Eric Kandel has shown that the processes for short term and long term memory differ. Short term memory causes the sensory neurons to release increasing amounts of neurotransmitter (presumably strengthening the connection). Long term memory results from the construction of new synapses. The hippocampus controls the formation of short term memories, but long term memories are shifted to the cerebral cortex. The author points out that memory retrieval is a separate process from memory formation.

As the new synapses require protein production, it can be seen to be the result of gene expression. Research has shown that histone acetylation and methylation are involved in the formation of long term memory. DNA methylation has also been shown to be involved. Researchers have suggested that DNA methylation may download epigenetic marks from the hippocampus to the cortex.

14 - Zooming in on Memory

Drugs called HDAC inhibitors prevent acetyl groups from being removed from histones, and have been shown to facilitate learning and memory in mice. Further experiments with mice have established that apparently forgotten memories could be restored by exposing the mice to an enriched environment, showing that the memories were not lost but inaccessible. HDAC inhibitors have also been shown to re-establish lost memories. However, the process of forgetting memories is also important, as it allows the organism to "get over" past anxieties.

15 - Nutrition

Fetal programming or development origins of health and disease (DOHaD) occurs when the experiences of pregnant mothers cause trends in the offspring. Women who are malnourished throughout pregnancy produce underweight children. If malnourished for the first two trimesters but not the third, the children are normal birth weight but begin eating ravenously 5 weeks later.

Many indications have shown maternal diet cause epigenetic expressions in the offspring. Further, an individuals diet has been shown the same effects. Broccoli sprouts have been shown to increase histone acetylation in white blood cells.

An experiment where rats with a tendency to become fat were fed the hormone leptin for 10 days after birth, the tendency was reversed and the rats grew normally.

16 - Zooming in on Nutrition

The agouti gene in mice affects cost color. It is controlled by a DNA segment called a retrotransposon as it can change its position within the genome. The methylation of this segment can vary from little to great and affects coat color over a continuum. The methylation of this retrotransposon has been shown to be affected by the mothers diet.

17 - Inheritance

While Lamarck believed that acquired characteristics could be inherited, an understanding of genetic mechanisms in the twentieth century led to the rejection of this concept in modern neo-Darwin evolutionary theory. Developmental Systems Theory (DST) regards evolution as a process whereby characteristics are developed using developmental resources including not only the genetic material but also community and the environment.

18 - Multiplicity

Epigenetic marks are erased between generations. However, there is evidence that DNA methylation can survive this erasure, supporting Lamarck's idea that acquired characteristics can be inherited.

19 - Evidence

Experiments have shown that the coat color of mice, determined by the degree of methylation of the Avy gene, can be influenced by the parents diet. Similar experiments have shown around the kinked tail gene. Diet effects have been demonstrated in the second generation (grandpups of mice), and beyond.

20 - Grandparents

A Swedish study indicated that when men had insufficient food during their slow growth phase of development (9 - 12 years), their children has reduced cardiovascular disease and their grandchildren were less likely to die from diabetes. Conversely, if excess food was available, the grandchildren had a fourfold increase in the risk of death due to diabetes. Other studies have shown that smoking and chewing of betel nuts can increase the risk of obesity in offspring.

While interesting, the possibility that the effects are the result of passing experience to the offspring cannot be eliminated.

21 - Caution

It is known that diseases are not caused by deterministic gene expression, but through interactions involving many of the components in a very complex system. The author cautions that epigenetic expression is not deterministic either. One should be cautious of books and articles that suggest that specific diet or lifestyle changes can target certain diseases.

22 - Hope

On the other hand, the author goes on to say that increasing knowledge of epigenetics will transform health care and further. As some epigenetic marks seem to be inheritable, the author believes studies "... might spur overdue changes to the neo-Darwinian understanding of evolutionary processes."

The author reviews a number of areas where epigenetics are being investigated as the basis for potential treatments, including aging, addiction, Alzheimers, PTSD, schizophrenia, bipolar disorder and depression.

The protein SIRT6 deacetylates histones associated with telomeres, which tend to shorten over time contributing to aging. In one experiment, mice were genetically engineered to overexpress SIRT6. These mice had significantly longer life spans than normal mice.

23 - Conclusions

The author summarizes the material.

[Simon Lavoie · Rating 5 out of 5]

Epigenetics are sets of chemicals that work as an interface between the genome and its environment. Food derived molecules like methyl and acetyl are its best known compounds. Binding on the DNA or on histone (proteins around which the genome rolls up), methyl or acetyl groups turn the transcription of specific genetic sequences on or off. It is a rather deep, unexpected mode of learning that may lead a population of genes to operate at 10%, 37%, 72% or any capacity in between (p.43), and that may transform a cell's structure and fonction permanently or temporarily.

The Developing Genome focuses on how such processes provide a missing causal link between
early events and later psychological outcomes. It is about behavioral epigenetics as a specific sub-field studying how molecular DNA and histone markers can influence "emotional reactivity, memory and learning, mental health" and other psychological processes (p.8), and vice versa (p.7). Each chapter or so that lays the main conceptual ground and general claim is followed by a harsher one that zoom in on the molecular workings. This two-step structure, along with Moore conveying his own amazement, help make this book thrilling.

The first part (chapters 1-7) covers the notions of phenotype, development, DNA and regulation, with the overall aim to prove wrong both the genome understood as the controller of phenotypic development, and the nature/nurture divide entrenched in the neo-darwinian framing of evolutionary thinking. To have x or y genes is not much relevant without knowing if these are activated or not, Moore writes in echo to the "genes for cancer" concern of many.
"The common belief that [genes] are things inside of us that constitute a set of instructions for building bodies and minds—things that are analogous to “blueprints” or “recipes”—is undoubtedly false. Instead, DNA segments often contain information that is ambiguous, and that must be edited and rearranged in context-dependent ways before it can be used" (p.26). The same segment of DNA can lead to very different outcomes depending on how it is alternatively spliced by RNA (whose epigenetic marking is not addressed, however) (p.33). "[T]he traditional idea that the genetic material in an individual’s body remains unchanged across the lifespan needs to be revised. We are all born with a developing genome, one that changes in response to its environmental context" (p.15).
How epigenetic markers differentiate the male from female chromosome and enter some specific disorder, as the Prader-Willy and the Angelman syndromes, are also addressed.

Hans Driesch (1867-1941) is said to have made a pioneering venture in epigenetics by explaining cellular differentiation in terms of a mechanism that preserve, but render unreadable in the specialized cell, the genetic sequences needed to produce any of the other 200 cell types that makes the whole organism. As François Jacob is credited for having shown, natural selection works like a tinkerer rather than an engineer, by trying past solutions to new problems (extending the epigenetical blinding of post-differentiated cells to multiple other areas) The second part (chapters 8-16) follow this line of thought while concentrating on contemporary key experiments on animals and humans, including that of Michael Meany's team at McGill on low vs high licking and grooming rat impacting stress regulation, and other experiment on suicide victims, on post-traumatic stress disorder and Alzheimer. Some converging experiments highlight how enriched environment (with peers, play and task) or, absent such environment, small RNA injection, help memory recovery (or de-acetylation of gene sequence promoting memory erasure). Moore also highlights Alan John's study, based on the Dutch Hungerwinter, as having shown how "woman’s food intake dur- ing pregnancy can influence her hormones in ways that can generate long-lasting effects in her children’s brains" (p.126).

The third part (chapters 17-20) addresses the issue of the generational transmission of epigenetics despite the Weisman barrier (the stage in the germ cells formation where somatic cells loose their epigenetic markers). The said barrier is a "central tenet of biological determinism (phenotypes are strictly determined by genes)". Despite being cautious with animal model, Moore take experiments on the transgenerational transmission via the male line of highly methylated hypothalamus cell as evidence that "natural selection should be able to operate on “inheritable” phenotypes that depend on epigenetic factors just as surely as it operates on phenotypes that depend on genetic factors" (p.175). Despite "[n]o data [being] currently available regarding the transgenerational transmission of epigenetic marks in human" (p.179), Moore rejoins the proponents of the Developmental System Theory in kicking genetic heritability from its pedestal, for reasons alluding in part to the possible existence of a distinct epigenetic code, buried in and passed along the genetic code, which we only scratched so far. Other reasons have to do with the claim that "all characteristics are “acquired characteristics,” because they are not present in zygotes and therefore have to be acquired during development. [... ] What matters in evolution is that characteristics be transmitted from generation to generation, regardless of how that happens" (p.155).

The last (chapters 21-23) focuses on the implications of the field, both in terms of cautions and hopes. Moore warns against taking epigenetic as a new determinism : "although nutritious diets and enriched environments are obviously important, human development is not a deterministic process, so our mature characteristics are no more determined by our epigenetics than they are by our genetics" (p.191). Although "we remain very far from being able to apply information about epigenetics in a practical way", treatments of Alzheimer, of post-traumatic stress disorder, addiction, schizophrenia and bipolar disorders are taken to allow for hope because of the advances in the field.

All in all, readers that are new comers to the field will gain valuable, probative insights from The Developing Genome. It contributes to sharpen our idea of how deep and transformative learning turns out to be : "If you had asked scientists a mere 20 years ago about how our bodies store information, they would have pointed to the neural networks in our brains, which retain information collected in our lifetimes, and to our DNA, which retains information that has survived natural selection across multiple generations. But if you ask well-informed scientists the same question today, they will point to the epigenome as another information repository in our bodies (p.131-2). Moore also drives quite elegantly one of the main take-home lessons of the curent developmental-system way of reframing the life science - psychology included: development is local, contingent, context-sensitive.

[Sulaf Farhat · Rating 1 out of 5]

Repetitive and uninspiring!

[Cheryl]

Got what I could from this dense and ten year old book. Interesting field; I'd be open to reading a new book on the topic. Pragmatically, probably not much is affecting our everyday lives; author's last paragraph admits that the advice on how to live well & how to raise healthy children remains the same as it has for centuries. It's always both nature and nurture, unto the generations.

August 2025

[Floyd22 · Rating 3 out of 5]

Even so it’s a really interesting book, it offers no scientific groundbreaking discovery in the field of Epigenetics. It’s mostly a recap oh Highschool biology.

[Harmen de Jong · Rating 4 out of 5]

Erg populair, die epigenetica, je leest er regelmatig wat over. Dit boek legt uit waar het over gaat. Ik ga geen samenvatting geven, dat zou neerkomen op het bijna volledig overschrijven van het boek. Volgens de schrijver kunnen we (nog?) niet zoveel met epigenetica. Het geeft wel inzicht in de mechanismen bij het ontstaan van persoonlijkheden, ziekten, haarkleur enz. Het idee dat je eigenschappen op je genen vast liggen en van alles voor je bepalen is niet helemaal juist. Je DNA is erg interactief met de omgeving. Als er in de omgeving hongersnood is, dan passen je genen zich aan via epigenetische processen. Zo wordt een foet voorbereid op de wereld waarin het terechtkomt. Maar als die omgeving veranderd is, dan heb je mogelijk een probleem, je stofwisseling staat verkeerd afgesteld. Om dat soort dingen gaat het. Effectief speelt epigenetica in de geneeskunde vrijwel geen rol, maar er wordt veel onderzoek gedaan. De verwachting is dat dat op termijn wel gevolgen zal hebben op allerlei gebieden.

[Cecily Winter · Rating 5 out of 5]

A fairly complex but wonderful overview of the development of the epigenome; fabulous for readers with a basic grasp of biology.

[Christopher Cockrum · Rating 5 out of 5]

Very interesting. Explains a lot.

[Mehrsa · Rating 2 out of 5]

Good information but old for nowadays

[Raveen Kulenthran · Rating 5 out of 5]

I read this book twice - I drew on it to motivate the modulation of my behaviour. I have also used it to inform my work as a manual therapist. The analogies Professor Moore uses made it such an easy book to comprehend, and there were many sentences in it that created 'Aha!' moments in me. I will come back to it every time I need to brush up on my knowledge of Genetics and Epigenetics.

[Flamingo · Rating 4 out of 5]

It was a really solid intro to behavioral epigenetics for me. The explanations were detailed enough for me to appreciate the complexity and intricacies of the subject and simple enough to prevent getting me confused.

Recommend if you're interested to learn about behavioral epigenetics.