October 2, 2018
Written by: Barbara Terzic
Did you really inherit your mother’s inclination to math and father’s intense fear of spiders? Or are our personalities a product of our upbringing rather than genetics? We know the environment we grow up in can influence the path our lives take, but to what extent does it shape who we are and what we become? The field of behavioral epigenetics attempts to understand this by studying how nature, our biological heredity, is shaped by nurture, everything else that occurs in your life-span (e.g., social experience, diet and nutrition, exposure to toxins, etc.).1
When we talk about ‘nature’ what we really mean is our DNA, the backbone of each of our cells that carries genetic information critical for their growth, function, and survival. You can think of this hereditary, self-replicating material as the master blueprint telling each cell in our body what it needs to do, such as express genes (i.e., generate proteins) that execute all its essential functions. Interestingly, even though every cell in our body contains the exact same DNA code, each cell has a fine-tuned system for expressing only a subset of genes encoded by all of our DNA, and at specific time points. This phenomena of controlling gene expression is explained by epigenetics, and you can read more about it in a previous week’s article here! Simply summarized, epigenetics describes the modifications placed on top of our DNA material that control which genes are expressed when, and to what magnitude (like earmarks). It is what underlies our ability to generate many different types of cells (e.g., liver cells versus skin cells versus brain cells) all with one, identical DNA code. Importantly, these different modifications to our DNA in different cells are known to be influenced by our environment (the ‘nurture’ aspect, if you will), allowing our bodies to alter the expression of our genes without altering the core DNA blueprint itself, and providing us with the ability to adapt to external cues.
The specific repertoire of gene expression in different cells of our brain is critical for shaping brain circuitry during and after development. However, the extent to which subtle changes in our gene expression can affect complex behaviors, such as cognition, mental health, and personality, remains an active area of research. Environmental influences onto specific epigenetic marks have been linked to increased risk to addiction, certain eating disorders, learning/memory performance, and mental illnesses such as bipolar, major depressive disorder, psychopathy, and schizophrenia.2,3,4 Over the last decade, the work contributing to this field has grown exponentially, and is too extensive to properly describe here. However, there are two important examples to highlight:
Example 1: Twinning Thoughts
How do we test this nurture versus nature hypothesis? To truly confirm epigenetics as the culprit, we need identical, underlying DNA codes between test subjects. Scientists have been studying behavioral differences between identical—otherwise known scientifically as monozygotic—twins for some time now exactly for this reason. Monozygotic (MZ) twins (Figure 1) arise from a single fertilization event and later split to develop into two distinct human beings. Although they may look identical and carry the same genetic code, early studies have profiled epigenetic differences between twins, and many twins have been reported to present discordant personalities, risk-taking behaviors, and disease susceptibilities. Longitudinal studies have demonstrated that epigenetic variation is low at birth between MZ twins, but appears to increase with age, lending support to the idea that our environment may be capable of modulating our epigenome over time.5
One famous, early example stems from a small clinical study published in 2008 looking at differences in risk-taking behavior between two MZ twins. The subjects, referred to as ‘War Twin’ and ‘Law Twin,’ were described as taking extremely divergent life paths with one becoming a nomadic war journalist, and the other an assistant in a law office. The sisters also performed contrastingly on standard psychological evaluations, with one displaying risk-taking behaviors and the other displaying high risk-aversion and anxiety. Interestingly, the researchers also found epigenetic differences in DNA methylation (a specific kind of epigenetic DNA modification) at a gene known as DLX1 correlated with their differing behaviors.6 DLX1 encodes a protein that serves as a master ‘regulator’ of many other genes, and affecting its expression is known to have many drastic effects particularly during brain development.7
Could varying epigenetic marks be underlying these distinct personalities and life paths between these identical sisters? Is DLX1 an important genetic regulator of behavioral traits such as risk-taking? To truly prove this, we would need to artificially manipulate DNA methylation around DLX1 to see if it is capable of directly influencing risk-taking behavior. Since doing this in humans is technically unethical, and truckloads of age-matched, human twins willing to participate in scientific studies are difficult to come by, scientists have had to become a little more creative in their experimental design. Which brings us to:
Example 2: Bugs Life
Social insects such as ants and bees have recently been emerging as a unique model system to study the effects of gene regulation on behavior for two main reasons: 1) their colonies consist of a unique caste system wherein each individual performs a specialized task/behavior and 2) all members of the hive/colony are derived from the exact same genome. So, many different behaviors, but identical underlying DNA blueprints! Most ant colonies include one ‘queen’ that carries out all the egg-laying, and numerous ‘workers’ who focus on all other tasks such as foraging and building. In a recent study by researchers at the University of Pennsylvania, scientists were able to use epigenetic manipulations to artificially alter the social and reproductive behavior of ants within one colony.
Within the Indian jumping ant species (Harpegnathos saltator; Figure 2), when their queen dies, other female worker ants change into “pseudo-queens” and battle for dominance over the colony. To summarize a lot of work quickly, the researchers in this study found that levels of a specific epigenetic regulator, corazonin, were important in altering gene expression in these ants to become either workers, hunters, or queens during this transition, where high levels of corazonin drove ants to remain worker-specific. By artificially manipulating corazonin levels in their ants, the researchers were able to preferentially drive the ants to become either pseudo-queens or workers!8 More importantly, this same role for corazonin was seen in other social insect species such as wasps, bees, and termites.
In honey bees (Apis mellifera), genetically identical larvae become either queens, sterile female workers, or male drones, and it turns out nurture, not nature, is the critical factor driving this division within the hive. In fact, scientists have shown that the type and amount of food as well as cell space a larva develops in can drastically alter its DNA methylation pattern.9,10 This epigenetic pattern is in turn critical for determining which of the three above castes a larva will be categorized into. Additional studies have looked at the role of a specific epigenetic modifier, DNMT3, in this developmental trajectory, where turning down DNMT3 levels drove larvae to all become queens instead of workers. These results suggest that the flexibility of epigenetic modifications over thesame underlying DNA code can have profound implications on behavioral status and social ‘caste’ in these species.11
These foundational studies have paved the way for future work in vertebrates looking at the importance of epigenetics and gene regulation in physiology and social behavior, but there is still much more work to be done in order to truly understand the exact modifications underlying different traits. One thing we can be sure of, however, is that our heredity is not necessarily our destiny. So whenever in doubt, just remember: queens are made, not born.
1Moore DS. The developing genome: an introduction to behavioral epigenetics. 2015; (1sted.), Oxford University Press.
2Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodeling. Nature.2007; 447(7141), 178-182.
3Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nature Reviews Neuroscience.2011; 12(11), 623–637.
4Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aeali B, Carnevale J, Pan H, Papageorgis P, Ponte JF, Sivaraman V, Tsuang MT, Thiagalingam S. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Human Molecular Genetics. 2006; 15(21), 3132–45.
5Chatterjee A & Morison IM. Monozygotic twins: genes are not the destiny? Bioinformation. 2011; 7(7), 369-370.
6Kaminsky Z, Petronis A, Wang SC, Levine B, Ghaffar O, Floden D, Feinstein A. Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior. Twin Research and Human Genetics. 2008; 11(1), 1-11.
7Hamilton SP, Woo JM, Carlson EJ, Ghanem N, Ekker M, Rubenstein JLR. Analysis of four DLX homeobox genes in autistic probands. BMC Genetics. 2006; 6, 52.
8Gospocic J, Shields EJ, Glastad KM, Lin Y, Penick CA, Yan H, Mikheyev AS, Linksvayer TA, Garcia BA, Berger SL, Liebig J, Reinberg D, Bonasio R. The neuropeptide corazonin controls social behavior and caste identity in ants. Cell. 2017; 170, 748-759.
9Ashby R, Forêt S, Searle I, and Maleszka R. MicroRNAs in honey bee caste determination.Scientific Reports. 2016; 6, 18794
10He XJ, Zhou LB, Pan QZ, Barron AB, Yan WY, and Zeng ZJ. Making a queen: an epigenetic analysis of the robustness of the honeybee (Apis mellifera) queen developmental pathway. Molecular Ecology. 2017; 26(6), 1598-1607.
11Kucharski R, Maleszka J, Foret S, Maleszka R. Nutritional control of reproductive status in honeybees via DNA methylation. Science. 2008; 319, 1827-1830.
Cover Image: pxhere; free of copyrights under Creative Commons CC0; https://pxhere.com/en/photo/923608
Figure 1: Photo by Christopher Michel via Flickr; CC-by-2.0; https://www.flickr.com/photos/cmichel67/14146231281/
Figure 2: Image by Kalyan Varma via Wikimedia Commons; CC BY-NC-ND 2.0; http://kalyanvarma.net/photography