Epigenetics is the study of how specific genes can be turned on or off without changing the underlying DNA sequence. This can happen in response to the environment, such as what a person eats or whether they smoke.
Some epigenetic changes can be passed down from one generation to the next. That means that if your parents had a certain gene turned off, that gene might also be turned off in you. Researchers have found that this can happen up to three generations down.
According to the findings of the research study that was just recently published, an epigenetic modification can be passed down via sperm not only from parents to offspring but also to the subsequent generation, which is also referred to as “grand offspring.”
This is called “transgenerational epigenetic inheritance.” It happens when epigenetic marks (attached to chromosomes) are changed. This leads to different gene expressions in offspring and grand offspring.
Epigenetic modifications are changes that can happen to genes without changing the code in the DNA. This can affect an organism’s health and how it develops. The idea that these changes in gene expression can be passed down from parents to children was once considered very strange. But now there is more evidence to support it. Even so, we do not yet understand all the mechanisms involved.
Following an exciting hypothesis, researchers at the University of California, Santa Cruz, have published a new study demonstrating how a common type of epigenetic modification can be passed on to grand offspring in some cases.
They hypothesized that if a particular configuration of DNA packaging is preserved in the germline (a lineage of germ cells, each of which descended or developed from earlier cells in the lineage and which is considered to continue through successive generations of an organism), it has the potential to be passed down through a significant number of generations.
This type of epigenetic inheritance may explain how the experiences of a person’s parents and grandparents can affect that person’s health and development later in life.
The sperm of worms
So far, the research is centered around the sperm of nematode worms (Caenorhabditis elegans, or C. elegans), but the scientists say it applies to every multicellular animal, including human beings.
The findings of this study were presented in a paper published in the Proceedings of the National Academy of Sciences (PNAS). The paper focused on a specific modification of a histone protein that alters how DNA is packaged within the chromosomes. This epigenetic mark, known as H3K27me3, has been studied extensively because it is known to turn off, or “repress,” the affected genes.
According to the study’s corresponding author, Susan Strome,
“This seems like a conserved feature of gene expression and development in animals, not just a weird worm-specific phenomenon,” she said.
Testing science on animals
The scientists were able to conduct remarkable genetic experiments on C. elegans that would not be possible for them to carry out on humans, and the findings of these experiments have the potential to have far-reaching implications for the biology of other organisms.
Their research findings establish a cause-and-effect relationship between sperm-transmitted histone marks and gene expression and development in offspring and grand offspring.
The primary proteins responsible for packaging DNA within the chromosomes are known as histones. The methylation of a specific amino acid in the histone H3 is what is meant when people talk about the epigenetic mark known as H3K27me3. Because of this, the DNA ends up being packaged more densely, making it more difficult for the genes in that region to be activated.
Using C. elegans embryos to carry out research
To investigate epigenetic inheritance, researchers created embryos of the worm C. elegans that inherited egg chromosomes that were properly packaged with the epigenetic mark H3K27me3 and sperm chromosomes that lacked the mark. These embryos were passed on to the next generation.
What the scientists did and the potential implications of their findings
In the most recent research, a particular histone mark was removed from the chromosomes of C. elegans sperm. These sperm were then utilized to fertilize eggs that had their chromosomes completely marked.
A histone mark is a chemical modification to a histone protein that can affect how the DNA wrapped around the histone is expressed. A histone protein is a protein that helps to package and organize DNA in cells. In the study, the researchers removed a histone mark from the sperm of a species of worm called C. elegans. They then used those sperm to fertilize eggs that had all of their histone proteins marked. The researchers found that the eggs fertilized with unmarked sperm could not develop properly.
In the offspring that were produced as a result of this experiment, the researchers discovered abnormal patterns of gene expression. Specifically, they found that genes on the paternal chromosomes (inherited from the sperm) were “upregulated” or turned on, despite the absence of the repressive epigenetic mark.
Consequently, tissues expressed genes that they would not have normally expressed under normal circumstances. For example, gene expression that is normally only found in neurons was found in germline tissue, which is the tissue that produces eggs and sperm.
According to Strome, aberrant gene expression was found in all of the tissues the researchers examined. However, different genes were found to be upregulated in each of the tissues, demonstrating that the context of the tissue determined which genes were turned up.
An examination of the chromosomes in the germline tissue of the offspring revealed that the upregulated genes had not yet regained the repressive histone mark. In contrast, the mark had been reinstated on the genes that had not been affected by the upregulation.
Strome explained that in the germline of the offspring, some genes were abnormally turned on and remained in the state of lacking the repressive mark, while the rest of the genome regained the mark. This pattern was passed on to the grand offspring, and it continued in the same way.
The researchers observed various developmental effects in the grand offspring, including some completely sterile worms. This was one of the more concerning findings. The research is perhaps suggesting that sterility can be tracked to grandparents and triggers in their environment. This potentially has enormous implications for what we know about how to treat infertility.
This variety of outcomes is caused by how chromosomes are distributed during the cell divisions that produce sperm and eggs. As a consequence, there are a great number of distinct chromosome combinations that can be passed on to the following generation.
It is often the case that when scientists alter the DNA of animals, offspring can be sterile, but in other recent scientific research, other scientists have recently made a breakthrough in creating mutant rats that can breed.
