When it comes to regeneration, some animals can have amazing performances – if you cut the leg off a salamander, it will grow back. When threatened, some cakes release their tails as a distraction and regain them later.
Other animals take the process even further. Planar worms, jellyfish and sea anemones can actually regenerate the entire body after cutting in half.
Headed by Assistant Professor of Organic and Evolutionary Biology Mansi Srivastava, a team of scientists spreading new light on how animals pull off, and revealed a number of DNA switches that seem to control genes for whole-body regeneration. The study is described in a March 15 paper in Science .
Using three-band panther worms to test the process, Srivastava and Andrew Gehrke, a graduate student working in her lab, found that a section of non-coding DNA directs the activation of a "master control gene" called early growth response. or EGR. Once active, EGR controls a number of other processes by switching on or off other genes.
"What we found is that this main gene comes on … and it activates genes that turn on during regeneration," says Gehrke. . "What happens is that the non-coding regions say the coding regions should turn on or off, so a good way to think about it is as if they were switching."
In order for the process to work, Gehrke said, DNA in the mask's cells, which is normally properly folded and compressed, must change, making new areas available for activation.
"Many of the very tightly packed parts of the genome are actually physically more open, because there are regulatory switches where that must be turned on or off," he says. "So one of the great results in this document is that the genome is a lot dynamically and truly change during regeneration when different parts are opened and closed. "But before Gehrke and Srivastava could understand the dynamic nature of the mask's genome, had to mount its sequence ̵
" a large part of this paper – we release the genomes of this species, which is important because it is the first of this phylum, "Srivastava said." So far there had been no complete genome sequence available. "
And that is also remarkable, she said, because the three banded panther mask represents a new model system for studying regeneration.
"Previous work with other species helped us learn m steam things about renewal, "she 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 how they are related to other animals … lets us make statements about evolution.  "The second reason is that they are really good lab rats," she continued. "I collected them in the field in Bermuda a few years ago during my postdoc and since we have taken them into the lab, can be used for much more tools than any other system."
And while these tools can demonstrate genome's dynamic nature during Regeneration – Gehrke was able to identify as many as 18,000 regions that are changing – what's important she said is how much meaning he could derive from studying them.
The result, she said, shows that EGR acts as a switch for regeneration – when it is turned on, other processes can occur, but without it, nothing happens.
"We could reduce the activity of this gene and we found it If you don't have Egr, nothing happens," says Srivastava. "The animals just can't regenerate. All of these downstream genes will not turn on, so the other switches will not work, and the whole house will go dark, basically. "
While the study reveals new information on how works work 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 downstream are present in other species, including humans," says Gehrke.
"The reason we called it This gene in the worms Egr is that when looking at the sequence, it resembles a gene that has already been studied in humans and other animals, says Srivastava. "If you have human cells in a dish and stress them, if it's mechanical or you put toxins on them, they will express Egr immediately."
"But the question is: If people can beat Egr and not just put it on, but do it when our cells are damaged, why can't we regenerate?" Srivastava said. "The answer may be that if EGR is the switch we think What the EGR is talking about in human cells can be different from what it speaks in the three-band panther mask, and what Andrew has done with this study has come up with a way to get that lead. want to find out what these connections are and then apply it to other animals, including vertebrates that can only do more limited regeneration. "
Forward, Srivastava and Gehrke said that they hope to investigate whether the genetic switches are activated during regeneration are the same as those used during development and continue to work to better understand the genome's dynamic nature.
"Now that we know what the switches are for regeneration, we look at the switches involved in the development, and whether they are the same," says Srivastava. "Are you just developing again, or is it another process involved?"
The team is also working to understand the exact ways in which EGR and other genes activate the regeneration process, both for three-band panthermas and for other species.
In the end, Srivastava and Gehrke said that the study highlights the value, not just to understand the genome, Without understanding the whole genome – the non-coding and the coding parts. "" Only about two percent of the genome does things like proteins, "said Gehrke." We wanted to know: What are the other 98 percent of the genome being done throughout body regeneration? People have long known that many DNA changes that cause disease are in non-coding regions … but it has been undervalued for a whole-body generation process.
"I think we've just scratched the surface," he continued. "We have looked at some of these switches, but there is a completely different aspect of how the genome interacts on a larger scale, not just how bits are opened and closed, and all that is important for turning on and off genes, so I think that there are several layers of this regulatory framework. "
" It is a very natural matter to look in the natural world and think if a gecko can do this, why can't I, Srivastava says. "There are many species that can regenerate and others who cannot, but it turns out that you compare the gene over all animals, most of the genes we have are also found in the three banded panthermasks … so we think some of these answers will probably not to get rid of if certain genes are present, but from how they are linked or networked together, and that answer can only come from the non-coding part 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 Institute of Health, the Biomedical Major Education Program, UC Berkeley , Marthella Phosphorus Brown Chair in Biological Sciences, and Howard Hughes Medical Institute.