When it comes to regeneration, some animals are capable of incredible feats: if you cut the leg from a salamander, it will grow back. When threatened, some geckos release the tail as a distraction, and grow back later.
Other animals continue the process. Planar worms, jellyfish and sea anemones can actually regenerate their bodies after being cut in half.
Led by assistant professor of Organismic and Evolutionary Biology Mansi Srivastava, a team of researchers is shedding new light on how animals bring out the enterprise and has discovered a number of DNA switches that seem to control genes for regeneration of the whole body. The study is described in a March 15 article on Science .
Using three-band worms to test the process, Srivastava and Andrew Gehrke, a post-doctor working in his laboratory, discovered that a non-coding DNA section controls the activation of a "control gene principal "called early growth response, or EGR. Once active, EGR controls a number of other processes by activating or deactivating other genes.
"What we discovered is that this main gene turns on … and this is the activation of genes that light up during regeneration," said Gehrke. . "Basically, what's happening is that the non-coding regions are telling the coding regions to turn themselves on or off, so a good way of thinking is as if they were switches."
For that process to work, Gehrke said, DNA in worm cells, which is normally folded and tightly packed, must change, making new areas available for activation.
"Many of these very narrow portions of the genome become more physically open, because there are regulatory switches that must activate or deactivate genes," he said. "So one of the great discoveries in this article is that the genome is very dynamic and really changes during regeneration while different parts open and close."
But before Gehrke and Srivastava could understand the dynamic nature of the worm genome, he had to assemble his sequence ̵
"This is an important part of this article – we are releasing the genome of this species, which is important because it is the first of this phylum," said Srivastava. "Until now there had been no complete genome sequence available."
And it is also noteworthy, he said, because the three panther worm represents a new model for the study of regeneration.
"Previous work on other species helped us learn a lot about regeneration," he said. "But there are some reasons to work with these new worms, one of which is that they are in an important phylogenetic position, so the way they are related to other animals … allows us to make statements about the evolution.  "The other reason is that they are really fantastic laboratory mice," he continued. "I collected them in the field in Bermuda several years ago during my post-doctorate, and since we took them to their laboratory "reusable with many more tools than other systems."
And while these tools can demonstrate the dynamic nature of the genome during regeneration – Gehrke was able to identify up to 18,000 changing regions – what is important said is the meaning that was able to derive from the study.
The results, he said, show that EGR acts as a power switch for regeneration: once switched on, other processes can take place, but without it, nothing happens.
"We have been able to decrease the activity of this gene and we have found it if you have no Egr, nothing happens," said Srivastava. "Animals can't regenerate, all downstream genes don't turn on, so the other switches don't work, and the whole house becomes dark in practice."
While the study reveals new information on how the process works in worms, it can also help explain why it doesn't work in humans.
"It turns out that Egr, the main gene and the other genes that are turned on and off in the valley are present in other species, including humans," said Gehrke.
"The reason we called this gene in Egr worms is because when you look at its sequence, it is similar to a gene that has already been studied in humans and other animals," said Srivastava. "If you have human cells in a dish and put them under stress, whether they are mechanical or that toxins, they immediately express Egr.
" But the question is: if humans can turn on Egr, and not just turn it on, but do it when our cells are injured, why can't we regenerate ourselves? "said Srivastava." The answer might be that if EGR is the power switch, we think the wiring is different. What the EGR is talking about in human cells may be different from what it is talking about in the panther's three-band worm, and what Andrew did with this study is to find a way to get this connection. So we want to understand what these connections are, and then apply them to other animals, including vertebrates that can only do a more limited regeneration. "
Going forward, Srivastava and Gehrke said, they hope to investigate 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.
"Now that we know which switches are for regeneration, we are looking at the switches involved in development, and If they are the same," said Srivastava. " Have you just done the development again, or is a different process involved? "
The team is also working on understanding the precise ways in which EGR and other genes activate the regeneration process, both for three-banded panther worms and for other species.
In the end, Srivastava and Gehrke they said, the study highlights the value not only of understanding the genome, but of understanding the entire genome – non-coding and coding portions.
"Only about two percent of the genome produces things like proteins", has said Gehrke. "We wanted to know: what is the other 98 percent of the genome during the regeneration of the whole body? People have known for some time that many DNA changes that cause the disease are in non-coding regions … but it has been underestimated for a process like regeneration of the whole body.
"I think we have just scratched the surface," he continued. "We examined some of these switches, but there is another aspect of how the genome is interacting on a larger scale, not just how the pieces open and close, and this is important to activate and deactivate. genes, so I think there are more levels of this normative nature. "
" It's a very natural question to look at in the natural world and I think, if a gecko can do this because I can't, "said Srivastava." There are many species that can regenerate, and others that cannot, but it turns out if we compare genomes through all animals, most of the genes we have are also in the panther three-stripe worm … so we think some of these These answers probably do not come from the fact that some genes are present or not, but from the way they are wired or networked, and this response can only come from the non-coding portion of the genome. "
This research was supported with funding from the Milton Fund of Harvard University, the Searle Scholars Program, the Smith Family Foundation, the National Science Foundation, the Helen Hay Whitney Foundation, the Human Frontier Science Program, the National Institutes of Health, the Biomedical Big Training Program, the UC Berkeley, the brown chair Marthella Foskett in Biological Sciences and the Howard Hughes Medical Institute.