Written by Anna Zhebrun, Rutgers School of Arts and Sciences, Class of 2022.
Anna is majoring in Molecular Biology & Biochemistry and minoring in Chemistry.
From introductory science classes to general biology, we have been taught that all organisms are coded by deoxyribonucleic acid (DNA). Our grandparents gave a portion of their genetic code to our parents, our parents gave a portion of it to us, and we will provide some of that genetic code to our kids. Nothing more, nothing less; after all, Lamarck’s theory of passing down acquired characteristics has been shunned for nearly as long as it existed.
If you don’t know who Lamarck is, just think of giraffes. I’m sure that will trigger a distant memory, because Lamarck is the scientist most infamously known for his conclusion that giraffes evolved their long necks through continuous generations of giraffes reaching for leaves higher and higher above the ground. Over time, their necks got longer and longer and they passed on these elongated necks to their kids. After many generations, we now have very long-necked giraffes.
Of course, if you remember back to general biology, this is not how giraffes acquired their long necks, and with our current scientific knowledge, Lamarck’s theories seem absurd. Can you just imagine if we passed down any characteristic we acquired during our own lifetime? It would be cool, of course, for a child to have natural pink hair because at one point or another one of their parents dyed their hair pink. However, we all know that this does not happen. Still, it would be very unscientific to completely disregard an idea without exploring its every angle. Even if most acquired characteristics won’t be passed down to future generations, there might be significant exceptions.
There is now a variety of evidence that demonstrates that traumatic events during a parent’s lifetime can negatively impact their future children. One example of this is that the grandchildren of survivors of the Dutch famine of World War II seem to have lower than normal average weight. Many other studies show a variety of experiences that result in the acquisition of a heritable phenotype (visibly expressed characteristic resulting from genetic code) that wasn’t present in generations before the experience occurred. So, if DNA codes for everything we are, and we have effective ways of preserving it, how can the experiences of a parent affect the phenotype of their offspring? Well, it turns out that the way our DNA code is expressed is much more complicated than just translating the code into proteins.
In a cell, DNA is coiled around special proteins called histones. Different parts of the DNA can be packed around histones looser or tighter, allowing different parts of the DNA strand to be more or less accessible to the proteins responsible for transcribing the DNA into messenger ribonucleic acid (mRNA). This mRNA is then used as a template to build proteins. One modification could be the addition of a methyl group to certain parts of the histone by histone methyltransferases (HMTs). The methyl group regulates the level of access of the transcription machinery (the complex that synthesizes mRNA from the template DNA). Thus, HMTs affect the levels of mRNA synthesis, which directly influence the amount of proteins created. In that way, the phenotypes of genetically identical organisms may differ simply because of how their DNA is packaged.
Thus, understanding the inheritance of phenotypes is more than just a simple matter of looking at DNA. Cells have developed a variety of ways to regulate the expression of their DNA, such as the mentioned addition of methyl groups, and now there is evidence that such regulation could potentially be passed down through generations. For example, famine might trigger changes in gene expression that will continue to persist even in generations that have been brought up in times of surplus.
The idea that the modificational changes in the coiling of DNA around histones can be heritable, has created another field of genetics - epigenetics. Transgenerational epigenetic inheritance describes the passing of traits from parent to offspring that is affected not only by the DNA code, but by other markers that package it in one way or another. Understanding the ways in which such inheritance occurs requires time-consuming experimentation in research labs. One such lab is located here at Rutgers University: the Gu Lab. Their research focuses on studying the epigenetic inheritance in Caenorhabditis elegans, a type of microscopic nematode worm that is considered to be a model organism for studying genetic phenomena. Because of their small size and short generation times, experiments can be carried out across multiple generations within a reasonable time period.
Right now, the lab is focused on understanding how different proteins in the SET family that function like HMTs influence the establishment of transgenerational epigenetic inheritance. The C. elegans genome has been fully sequenced, meaning that we know all of the genes present in the organism. This allows for relatively easy modification of the worm genome using CRISPR/cas9 machinery. Using this machinery, the lab has modified multiple SET proteins to compare the phenotypes of worms who lose certain proteins to the phenotypes of their wild (naturally found) counterparts and exposed them to double stranded RNA that has been recognized as a trigger for transgenerational epigenetic inheritance. A lot of the experiments are being concentrated specifically on understanding the function of the protein SET-32, which has already been shown to play an important role in establishing epigenetic silencing at certain chromosome locations. This means that once silencing is established in one generation in response to a certain trigger, it persists for multiple generations even after the trigger is removed.
Thus, the little petri dishes holding these tiny worms might provide us with all the information we need to understand how different stimuli and experiences throughout a parent’s life can affect their offspring.
Photo Credits: (1) Pixabay; (2-4) Wikimedia Commons; (5) Anna Zhebrun.