Image: Henadzi Pechan/Canva

I was gobsmacked to learn that who I am, is not, in fact, composed of half Mom and half Dad. Neither are you. Those high school biology classes that slogged through Mendelian inheritance now feel like a sham, as if I had lost the shell game.

Gregor Mendel, the father of modern genetics, began the body of research that later scientists, including Theodor Boveri and Walter Sutton, expanded to arrive at the chromosome theory of inheritance. Each offspring receives 23 chromosomes from Mom and 23 matching chromosomes from Dad. Fifty-fifty right? We’re frequently reminded of this fact by gushing relatives. You said that just like your father. You smile just like your Mom.

You do have equal numbers of genes from both parents, but that’s not the whole story. It turns out there’s a stop code, running interference inside you, called imprinting. Imprinting is a process that basically flags the gene, so it becomes a mere placeholder, never contributing to the offspring’s development. So if Mom carries all the stop codes, she has fewer expressed genes — those that actually make stuff happen — in the end product, which is you. Same if Dad holds the stop codes.

The effects of these stop codes can determine whether someone develops certain diseases, with a growing awareness among scientists that they might even explain common mental health issues.

Silence of the genes

As recently as a few decades ago, few people imagined that genetic influences existed beyond what was already programmed in our inherited DNA. But when researchers at the University of Cambridge attempted to breed mice that carried two complete copies of only the male’s 20 chromosomes or two full copies of only the female’s 20 chromosomes — giving each mouse the 40 chromosomes needed to live — all the mice died.

The scientists realized there was more at play in developing a healthy mouse than a complete set of 40 chromosomes. There must be some interplay between Mom’s and Dad’s genetics that results in robust offspring. This and further breakthroughs eventually led to the discovery of imprinting.

Imprinting is a process that happens beyond genetics, and is therefore called epigenetic. An epigenetic event can change the expression of a cell’s gene without changing the basic genetic code. During imprinting, one or more molecules are added to the gene, acting as a stop code. These molecules tag the DNA and prevent it from being transcribed into proteins, therefore blocking the expression of that gene.

Imprinting adds a level of complexity to Mendelian genetics because it means inheritance is about more than 46 chromosomes. Genomic imprinting has overturned some of the most basic tenets of biology.

Scientists have identified approximately 90 genes that are imprinted. This delicate balance between gene expression and gene silencing from imprinting is necessary for healthy offspring and shapes who you are. But imprinting, out of necessity, will cause the unequal representation of Mom’s and Dad’s genes in the offspring.

Drum roll… who has the edge, Mom or Dad?

Studies in mice suggest that there is indeed an imbalance in gene expression (as imprinting would predict), and it favors fathers. An investigation published in Nature Genetics found that imprinted genes from the mother were 1.5 times more likely to be silent than those from the father. An earlier study in PLOS ONE produced similar findings. In the brain, the majority of active imprinted genes came from the father.

If these findings turn out to be true in humans, then a greater percentage of your father’s genes were expressed when you developed. Dad wins the gene game.

Which parent rules your brain?

By studying imprinted genes, researchers have uncovered clues about how our parents’ genes influence our brains. Certain regions are controlled almost entirely by the mother’s genes and other areas by the father’s. These conclusions came from several groundbreaking studies, one in which scientists developed mouse embryos comprised of solely paternal or only maternal chromosomes. This resulted in fetuses with mostly paternal or maternal expressed genes.

The mice with mostly paternal influence had smaller brains and larger bodies. Brain cells grew abundantly in the hypothalamus and septum, areas that maintain energy balance and mediate instinctual behaviors such as food seeking, mating, emotional expression, and social aggression.

Conversely, mice bred with mostly maternal influence had smaller bodies and larger brains — especially forebrains and regions involved in intelligence, complex emotional responses, planning, and problem-solving.

“The maternal influence is more on language and social executive function aspects of the brain, which are, in a sense, more complex,” says Janine LaSalle, a medical microbiologist at the University of California Davis, who was not involved in those studies but whose lab focuses on imprinting. The paternal influence seems more focused on survival.

That may be why more of Dad’s genes are expressed, I mean, if he’s the survival guy, I’m all in on that. But both are needed for the development of a whole brain.

“You need both Mom and Dad in order to get a normal brain,” LaSalle says. “We’re really at the beginning of understanding what that means.”

Imprinting errors explain several developmental syndromes.

When imprinting problems develop, the delicate balance between silent and expressed genes can go haywire, leading to disease and potentially death.

A rare developmental disorder like Prader-Willi syndrome can result, which affects one in 10,000 to 25,000 people. Irregular imprinting on chromosome 15 with the loss of needed paternal gene expression is the cause. Children with Prader-Willi syndrome have pituitary gland anomalies, a small brain stem, and atrophy in the cerebral cortex.

Other disorders like Beckwith-Wiedemann syndrome caused by the loss of maternal imprinting on chromosome 11 can develop when stop coding is messed up. Agnelman syndrome results from a reduction of maternally expressed proteins in a small section of chromosome 15. In other words, Dad’s genes were silenced as usual, but Mom’s genes were also imprinted and flagged for silence by mistake. These children have numerous issues, including hyperactivity and discoordination, and many develop autism.

Scientists are beginning to suspect that imprinting errors are responsible for more than just rare developmental disorders and could lead to illnesses like schizophrenia, Alzheimer’ disease as well as autism spectrum disorder.

For example, a recent study at the University of Pittsburgh that analyzed 14,400 samples from patients with dementia found that changes in two imprinting genes (DLGAP2/rs6992443; GPR1/rs16838070) were associated with increased risk for late-onset Alzheimer’s Disease. Another group which published their findings in Molecular Biologydetermined that a specific gene, GABRB2 appeared to be imprinted in schizophrenic offspring and may play a possible role in the development of the disease.

If scientists discover when and how imprinting goes awry, better therapies could be developed that focus on manipulating gene expression to prevent or offset imprinting errors. For example, RNA interference treatment, which allows doctors to dial down the expression of a targeted gene, such as a growth-related tumor gene, is being tested in several clinical trials.

In addition, the U.S. Food and Drug Administration approved two drugs for blood cell disorders, decitabine, and azacitidine, that prevent methyl groups (the stop code) from being added to genes in blood cells,

Now we know less than we thought we did

Though you may have always wanted to consider yourself expressing half Mom, half Dad, an even-stevens representation of their genetic codes, that isn’t the case. Be glad. If an interplay between your parents’ genes didn’t take place (imprinting), leading to an unequal gene expression, you wouldn’t be here.

The basic tenets of inheritance have been forever changed. A century’s worth of study in genetics, developmental biology, and neuroscience was based on inheritance concepts that are no longer true, which means that we understand far less than we thought we did.

“We’ve got a bunch of new stuff that, fundamentally, we don’t even know how to get our minds around,” says Jon Wilkins, Phd, an evolutionary theorist formerly with the Santa Fe Institute. But we can no longer consider ourselves as rough composites of our parents but rather as complex puzzle pieces crafted from thousands of maternal and paternal pieces over generations.