If we peek under the hood of the “sticky notes and highlighters” analogy, we are actually looking at a highly coordinated chemical process involving two main players: Small Non-Coding RNAs (sncRNAs) and DNA Methylation.
Here is exactly how an experience in the brain physically alters the DNA in a reproductive cell.
The Messenger: Small RNAs (sncRNAs)
When you think of RNA, you usually think of messenger RNA (mRNA). The molecule that reads your DNA and builds proteins. But the body also produces non-coding RNAs. When brain cells (neurons) fire together during a highly stressful event, they manufacture a specific type of sncRNA.
To get out of the brain, these sncRNAs are packaged into tiny protective bubbles called extracellular vesicles (or exosomes). Because they are safely packaged, they can survive the journey out of the brain, cross the blood-brain barrier, travel through the bloodstream, and pass through the barrier of the reproductive system to enter the sperm or egg cells.
Finding the Right Gene: Sequence Homology
How does the RNA know where to put the sticky note? The human genome has over 20,000 genes. If you learn to fear the smell of lavender, how does the RNA know to target the lavender receptor and not a gene for your liver?
It works through a matching system called sequence homology. The sncRNAs generated during the trauma are essentially mirror images of the active genes that were firing at the time (in this case, the specific olfactory receptor). When the sncRNA enters the reproductive cell, it floats along the massive strand of DNA until it chemically locks onto the exact matching sequence. The specific gene for that exact smell receptor.
The Sticky Note: DNA Methylation
Once the RNA has found its target, it recruits an enzyme called a DNA methyltransferase. This enzyme attaches a tiny chemical molecule, a methyl group (CH3) directly onto the cytosine bases of the DNA.
This process, known as DNA methylation, physically changes the shape of the DNA strand. It can cause the DNA to coil tighter (hiding the gene so it produces less of its receptor) or uncoil (exposing the gene so it produces more of its receptor).
In the famous cherry blossom experiment, researchers found that the specific gene responsible for detecting that scent (Olfr151) was chemically altered in the father’s sperm. When the offspring was born, that altered gene caused their brains to over-produce the receptors for that exact scent, leading to the oversized sensory reaction.
Reference:
- Dias, B. G., & Ressler, K. J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience
- Rechavi, O., Minevich, G., & Hobert, O. (2011). Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell