Epigenetic changes are transmitted through many generations
A new mechanism of epigenetic inheritance
may change our understanding of evolution
However, recent studies have shown that the reality is much more complicated: genes can be "turned off" in response to the environment and other factors, and sometimes these changes can also be transmitted from generation to generation.
The phenomenon, called epigenetic heredity, remains insufficiently studied and understood. Geneticist from the University of Maryland (UMD) Antony Jose, PhD, and two of his graduate students are the first who decided to find out the specific mechanism by which parents can transmit silent genes to their offspring. As the researchers found, this suppression, or silencing, of genes can persist for several generations – in their experiments in more than 25.
The study by Anthony Jose and his colleagues, published in the early online edition of Proceedings of the National Academy of Sciences (Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing), can significantly change our understanding of animal evolution, as well as help in the development of treatments for a wide range of genetic diseases.
"Scientists have long been interested in how information from the environment is sometimes transmitted to the next generation," says Dr. Jose, associate professor of cell Biology and Molecular Genetics at UMD. "This is the first mechanistic demonstration of how this can happen. This is a level of organization that we didn't know existed in animals before."
The researchers worked with the roundworm Caenorhabditis elegans, a species often used in laboratory experiments. Genetically modifying the nerve cells of worms, they "forced" them to synthesize double-stranded RNA (dsRNA) molecules corresponding to a specific gene. (RNA is a close relative of DNA and is represented in the body by many different variants, including dsRNA.) dsRNA molecules are known to move between the cells of the body (any cells except germ cells that produce eggs and spermatozoa) and can silence genes if their sequence "fits" to the corresponding part of the DNA of the cell.
The most significant discovery of Dr. Jose and his colleagues was that dsRNAs can move from somatic to germ germ cells and suppress genes in the latter. Even more surprisingly, this silencing can persist in more than 25 generations of C. elegans. This means that if such a mechanism exists in other animals (possibly including humans), then in response to the environment, a biological species can evolve in a completely different way.
The mechanism of gene silencing in C.elegans. Neurons (shown in purple) can export double-stranded RNA (orange arrow) corresponding to a specific gene (green) to germ germ cells, which leads to suppression of the expression of this gene in them (black). This silencing can persist in more than 25 generations of animals. (Figure from the press release New mechanism of inheritance could advance study of evolution, disease treatment – VM.)"This mechanism gives the animal a tool for much faster evolution," explains Dr. Jose.
"We still need to find out if this tool is actually used in this way, but it is at least possible. If animals use this kind of RNA transport to adapt, it will mean a new understanding of how evolution happens."
The long-term stability of the silencing effect is very important from the point of view of developing methods for the treatment of genetic diseases. The key to these techniques is a process known as RNA interference - the suppression of gene expression by dsRNA. As a potential method of gene therapy, this process has been studied for more than a decade, because it makes it possible to target the corresponding dsRNA gene of any disease. But the main obstacle here has always been the instability of silencing, which entails the need to reintroduce high doses of dsRNA to the patient.
"As a method of therapy, RNA interference is very promising, but the effectiveness of treatment decreases over time with each new cell division," explains Dr. Jose. "It is possible that this particular dsRNA, from C.elegans nerve cells, has some chemical modifications that ensure stable silencing for many generations. Further study of this molecule may help solve the problem of the effectiveness of RNA-based interference therapy."
Dr. Jose recognizes the big differences between a roundworm and a human. Unlike simpler animals, mammals know the mechanisms that reprogram silent genes in each new generation. At first glance, this would seem to exclude the possibility of epigenetic inheritance. And yet, the already available data suggest that the environment can cause a kind of transgenerational effect in mammals as well. Dr. Jose believes that his group's work offers a promising path to understanding how this happens.
"This is a fruitful area of research that will provide us with work for the next 10 or even more years," the scientist summarizes. "The goal is to achieve a very clear understanding –in simple terms – of all the tools that an animal can use for evolutionary development."
Portal "Eternal youth" http://vechnayamolodost.ru05.02.2015