Your Genes Are Not Your Destiny
On the importance of epigenetics
The concept of genetic determinism suggests that our genes dictate our destiny. However, emerging research indicates that genes are not as deterministic as once believed, as gene expression plays a pivotal role in shaping our traits and health outcomes. Indeed, why worry about a potentially pathogenic gene if it is never expressed?
A Tale of Dr. Jekyll and Mr. Hyde
To illustrate the power of gene expression, consider the relationship between a grasshopper and a locust. Although both insects share the same kingdom, phylum, and class, their behavioral characteristics differ significantly.
Surprisingly, grasshoppers and locusts are the same species and possess an identical genetic code. The distinction lies in differential gene expression. During periods of extreme environmental stress, such as famine or overpopulation, gene expression changes enable the transformation from a gentle grasshopper to a voracious locust.
The genetic code remains unchanged; rather, the same genetic instructions are reread, leading to vastly different phenotypic outcomes. This Jekyll-and-Hyde phenomenon raises an important question: Is genome rewriting necessary when gene expression alone can produce such drastic changes? Perhaps the centrality of genes in driving human health has been overstated.
Turn and Face the Strange
When discussing evolution, Charles Darwin is often the first name that comes to mind. However, Jean-Baptiste Lamarck, an 18th-century French naturalist and contemporary of Darwin, proposed a theory of "acquired characteristics."
Lamarck suggested that organisms could develop traits within their lifetimes and pass them to their offspring. Although the classic example of giraffes stretching their necks was used to discredit Lamarck's ideas, modern science reveals that he may have anticipated aspects of epigenetics.
Epigenetics is the study of heritable changes in gene expression that occur without alterations to the DNA sequence. The prefix "epi-" means "above" in Greek, indicating that epigenetic mechanisms act on top of the genetic code.
These changes determine whether genes are switched on or off and influence protein production. If the genetic code is considered the hardware of a computer, epigenetics functions as the software that controls the hardware's operations. Epigenetic changes regulate gene expression through several mechanisms:
The Sound of Silence: DNA Methylation
DNA methylation involves the addition of methyl groups to DNA bases, typically leading to gene silencing. This mechanism plays essential roles in:
X-Chromosome Inactivation: In females, one of the two X chromosomes is inactivated through methylation to prevent double expression of X-linked genes compared to males.
Cell Differentiation: Despite having nearly identical genetic material, somatic cells (skin, muscle, bone, nerve cells) exhibit different functions because specific genes are turned on or off via methylation.
The Packaging Problem: Histone Modification
Histone proteins, around which DNA is wrapped, can undergo chemical modifications that affect how tightly DNA is packaged. These modifications influence gene accessibility and expression.
The Hidden Orchestra: Non-Coding RNAs
Non-coding RNAs, such as microRNAs and long non-coding RNAs, can regulate gene expression post-transcriptionally by binding to messenger RNAs and preventing protein translation.
Leaving a Legacy
Notably, some epigenetic changes are transgenerational, meaning they can be passed down to future generations without changes to the DNA sequence or re-exposure to the original environmental factors. This inheritance occurs through the preservation of epigenetic marks during gamete formation and early embryonic development.
Epigenetics in Cancer Development
Epigenetic alterations are closely linked to cancer development. Two key phenomena characterize almost all human tumors:
Global Hypomethylation: Loss of methylation across the genome can activate oncogenes (genes that promote tumor formation), leading to uncontrolled cell growth.
Regional Hypermethylation: Increased methylation in specific regions can silence tumor suppressor genes, removing critical brakes on cell proliferation.
For example, cigarette smoke has been shown to:
Promote demethylation of metastatic genes in lung cancer cells, activating genes that facilitate cancer spread.
Induce hypermethylation of tumor suppressor genes, silencing their protective functions.
These findings indicate that inappropriate gene expression, rather than genetic mutations alone, increases the risk of tumor development.
Model Behavior
Given the crucial role of DNA methylation in humans, insights from genetic models lacking this epigenetic mechanism may not accurately reflect human biology. Epigenetic changes tend to be species-specific:
Saccharomyces cerevisiae (yeast) and Caenorhabditis elegans (roundworm): Do not exhibit significant DNA methylation.
Drosophila melanogaster (fruit fly): Displays minimal DNA methylation.
A 2018 study on C. elegans concluded that continuous expression of developmental growth genes contributes to aging. The authors suggested that these results could apply to humans. However, widespread DNA methylation in humans suppresses unnecessary gene expression during development.
Using models with similar epigenetic mechanisms is crucial when extrapolating findings to humans. Failing to account for gene expression may lead to incomplete or inaccurate disease and aging models, potentially resulting in adverse outcomes if applied to human gene editing experiments.
Rewrite the Story
Many determinants of gene expression are influenced by environmental and lifestyle factors within our control, including:
Diet and Nutrition: Nutrients like vitamin B12, folic acid, choline, and betaine act as methyl donors, affecting DNA methylation patterns.
Exercise and Lifestyle Choices: Physical activity and healthy habits can positively influence gene expression.
Sunlight Exposure and Circadian Rhythms: Natural light and sleep patterns impact epigenetic regulation.
Stress and Trauma: Psychological factors can induce epigenetic changes affecting mental and physical health.
Exposure to Pollutants: Environmental toxins, such as endocrine disruptors, can alter epigenetic marks.
Nutrigenomics: The Diet-Genome Connection
The interplay between nutrition and the genome has given rise to nutrigenomics, a field studying how dietary components affect gene expression and disease risk. Small changes in nutritional status, especially during critical development periods, can lead to significant differences in gene expression and physical characteristics in offspring.
Individuals are particularly susceptible to epigenetic influences during early developmental stages when epigenetic patterns are being established. Pregnant women can positively influence their children's epigenetic outcomes by:
Dietary Fortification: Consuming essential nutrients that serve as methyl donors supports proper DNA methylation.
Avoiding Harmful Substances: Abstaining from alcohol, tobacco, and exposure to pollutants reduces the risk of adverse epigenetic changes.
The interplay between genetics and epigenetics reshapes our understanding of human health and disease. While our genetic code provides the blueprint, gene expression and epigenetic regulation determine trait manifestation and disease susceptibility.
Recognizing that many factors influencing gene expression are within our control empowers individuals to make informed decisions that positively impact not only their health but also that of future generations.
Disclaimer: This article is intended for informational purposes and does not substitute professional medical advice. Always consult a qualified healthcare provider for personalized guidance.
This is the best article I've read on the subject. I finally understand all the jargon I had been plowing through, and can see real benefits from knowing epigenetics.
Thank you, Nita.
Really wonderful to read this information, and so well thought out. Brilliant.