Genetic Switch For Organ Regeneration Discovered By Scientists
Organ regeneration is a fascinating process which has enticed scientists for ages to research in the same field. Kingdom Animalia has species that are capable of regeneration, the leg of a salamander if cut will grow back, when threatened, some geckos shed their tails as a distraction and regrow them later.
As per the study published on March 15 in Science Journal, A team of Researcher Under Supervision of Assistant Professor of Organismic and Evolutionary Biology Mansi Srivastava is shedding new light on how creatures pull off the feat and uncovered a number of DNA switches that appear to control genes for whole-body regeneration.
Using three-banded panther worms to test the process, Postdoctoral fellow Srivastava and Andrew Gehrke working in their lab found that a section of non-coding DNA controls the activation of a “master control gene” called early growth response, or EGR. Once active, EGR controls a number of other processes by switching other genes on or off
Gehrke stated that – What they found was a one master gene comes on…and that’s activating genes that are turning on during regeneration. Basically, the non-coding regions are telling the coding regions to turn on or off, so to say in a more precise way they are working as switches.
Gehrke further stated that For that process to work, a change has to be made in the DNA worms’ cells, which is normally tightly folded and compacted making new areas available for activation.
He also said a lot of those very tightly packed portions of the genome actually physically become more open, because there are regulatory switches in there that have to turn genes on or off. One of the major findings in this paper is that the genome is very dynamic and really changes during regeneration as different parts are opening and closing.
But before understanding the dynamic nature of the worm’s genome Gehrke and Srivastava had to assemble its sequence–no easy feat in itself.
Srivastava stated that the biggest part of this study was released the genome of the species which is important because it is the first from this phylum.
And it is also noteworthy, she explained, because the three-banded panther worm represents a new model system for studying regeneration.
She stated- Previous work on other species helped us understand several things about regeneration, but there are some reasons to work with these new worms, one of which is they’re in an important phylogenetic position, so the way that they’re related to other animals allows us to make statements about development.
She continued further stating that another reason is they are really fantastic lab rats. She collected them in the area in Bermuda a few years ago during her post-doc, and since is was brought them to the lab they’re amenable to a lot more tools than a few other systems.
And while these tools can demonstrate the dynamic nature of the genome during regeneration, 18,000 regions were identified by Gehrke that changed
The results, she said, show that EGR acts as a power switch for regeneration–once it is turned on, other procedures can occur, but without it, nothing happens.
Srivastava stated they were able to reduce the activity of this gene and they found that if you don’t have EGR, nothing happens the animals just can not regenerate.
On one hand, the study reveals new details regarding how the method works in worms and on the other hand it also can help explain why it does not work in humans.
Gehrke stated that- It turns out that the master gene is EGR, and the other genes which are being turned off and on downstream are present in different species, including humans.
Post Doc Srivastava stated that- The reason they called this gene in the worm’s EGR is when you look at its sequence, it is very similar to a gene that has already been studied in humans and other animals.
Raising an interesting question Srivastava stated further If individuals can turn on Egr and not just turn it on but do it when our cells are injured, why can’t we regenerate? The answer could be that if EGR is the power switch, we believe the wiring differs. So they would figure out what those connections are, and then apply that to other animals, including vertebrates that could only do more restricted regeneration.
Moving forward, Srivastava and Gehrke stated that they are looking forward to investigating whether the genetic switches activated during regeneration are the same as those used during development and to continue working to better understand the dynamic nature of the genome.
Srivastava stated that- Now that they have understood what switches are for regeneration, they are looking at the switches involved in evolution, and if they are the same.
The group is also working on understanding the precise way that EGR and other genes trigger the regeneration process, both for three-banded panther worms, also for other species also.
At last together Srivastava and Gehrke stated that the analysis highlights the value not only in understanding the genome but understanding each of the genomes which include the non-coding as well as the coding portions.
Gehrke stated that Only about two percent of the genome makes proteins. They wanted to know about the role of other 98 percent of the genome doing during whole-body regeneration. People have known for some time that many DNA changes that cause disease are in non-coding areas but it’s been underappreciated for a procedure like whole-body regeneration.
He continued stating that they have only just scratched the surface. They have looked at a number of these switches, but there is a whole other part of how the genome is interacting with a larger scale, not just how bits open and shut, and all of that is essential for turning genes on and off, so I presume there are numerous layers of this regulatory nature.
Srivastava stated that – It’s a very natural question to look at the natural world and think if a gecko can do this why can’t they. He also said that there are many species that can regenerate and many can not but it turns out in case you compare genomes across all animals, the majority of the genes that we have are also in the three-banded panther worm.so they thought that some of those answers are probably not likely to come from whether or not certain genes exist, but from how they’re wired or networked together, and that answer can only come from the noncoding portion of the genome.
Read More: “Acoel genome reveals the regulatory landscape of whole-body regeneration” Science (2019).