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The genetics of regeneration: Study uncovers genes that control process of whole-body regeneration
news.harvard.edu/gazette ^ | March 14, 2019 | By Peter Reuell Harvard Staff Writer

Posted on 03/15/2019 6:16:58 AM PDT by Red Badger

When it comes to regeneration, some animals are capable of amazing feats. If you cut off a salamander’s leg, it will grow back. When threatened, some geckos drop their tails to distract their predator, only to regrow them later.

Other animals take the process even further. Planarian 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 pull off the feat, along the way uncovering a number of DNA switches that appear to control genes for whole-body regeneration. The study is described in a March 15 paper in Science.

Using three-banded panther worms to test the process, Srivastava and Andrew Gehrke, a postdoctoral fellow working in her lab, found that a section of noncoding 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.

“What we found is that this one master gene comes on [and activates] genes that are turning on during regeneration,” Gehrke said. “Basically, what’s going on is the noncoding regions are telling the coding regions to turn on or off, so a good way to think of it is as though they are switches.”

For that process to work, Gehrke said, the DNA in the worms’ cells, which normally is tightly folded and compacted, has to change, making new areas available for activation.

“A lot of those very tightly packed portions of the genome actually physically become more open,” he said, “because there are regulatory switches in there that have to turn genes on or off. So one of the big findings in this paper is that the genome is very dynamic and really changes during regeneration as different parts are opening and closing.”

Before Gehrke and Srivastava could understand the dynamic nature of the worm’s genome, they had to assemble its sequence — no simple feat in itself.

“That’s a big part of this paper,” Srivastava said. “We’re releasing the genome of this species, which is important because it’s the first from this phylum. Until now there had been no full genome sequence available.”

It’s also noteworthy, she added, because the three-banded panther worm represents a new model system for studying regeneration.

“Previous work on other species helped us learn many things about regeneration,” she said. “But there are some reasons to work with these new worms.” For one thing, they’re in an important phylogenetic position. “So the way they’re related to other animals … allows us to make statements about evolution.” The other reason, she said, is, “They’re really great lab rats. I collected them in the field in Bermuda a number of years ago during my postdoc, and since we’ve brought them into the lab they’re amenable to a lot more tools than some other systems.”

While those tools can demonstrate the dynamic nature of the genome during regeneration — Gehrke was able to identify as many as 18,000 regions that change — what’s important, Srivastava said, is how much meaning he was able to derive from studying them. She said the results show that EGR acts like a power switch for regeneration — once it is turned on, other processes can take place, but without it, nothing happens.

“We were able to decrease the activity of this gene and we found that if you don’t have EGR, nothing happens,” Srivastava said. “The animals just can’t regenerate. All those downstream genes won’t turn on, so the other switches don’t work, and the whole house goes dark, basically.”

While the study reveals new information about how the process works in worms, it also may help explain why it doesn’t work in humans.

“It turns out that EGR, the master gene, and the other genes that are being turned on and off downstream are present in other species, including humans,” Gehrke said.

“The reason we called this gene in the worms EGR is because when you look at its sequence, it’s similar to a gene that’s already been studied in humans and other animals,” Srivastava said. “If you have human cells in a dish and stress them, whether it’s mechanically or you put toxins on them, they’ll express EGR right away.”

The question is, Srivastava said, “If humans can turn on EGR, and not only turn it on, but do it when our cells are injured, why can’t we regenerate? The answer may be that if EGR is the power switch, we think the wiring is different. What EGR is talking to in human cells may be different than what it is talking to in the three-banded panther worm, and what Andrew has done with this study is come up with a way to get at this wiring. So we want to figure out what those connections are, and then apply that to other animals, including vertebrates that can only do 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 what the switches are for regeneration, we are looking at the switches involved in development, and whether they are the same,” Srivastava said. “Do you just do development over again, or is a different process involved?”

The team is also working on understanding the precise ways that EGR and other genes activate the regeneration process, both for three-banded panther worms and for other species as well.

In the end, Srivastava and Gehrke said, the study highlights the value of understanding not only the genome, but all of the genome — the noncoding as well as the coding portions.

“Only about 2 percent of the genome makes things like proteins,” Gehrke said. “We wanted to know: What is the 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 noncoding regions … but it has been underappreciated for a process like whole-body regeneration.

“I think we’ve only just scratched the surface,” he continued. “We’ve looked at some of these switches, but there’s a whole other aspect of how the genome is interacting on a larger scale, not just how pieces open and close. And all of that is important for turning genes on and off, so I think there are multiple layers of this regulatory nature.”

“It’s a very natural question to look at the natural world and think, if a gecko can do this, why can’t I?” Srivastava said. “There are many species that can regenerate, and others that can’t, but it turns out if you compare genomes across all animals, most of the genes that we have are also in the three-banded panther worm … so we think that some of these answers are probably not going to come from whether or not certain genes are present, but from how they are wired or networked together, and that answer can only come from the noncoding portion of the genome.”

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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 at UC Berkeley, the Marthella Foskett Brown Chair in Biological Sciences, and the Howard Hughes Medical Institute.


TOPICS: Business/Economy; Health/Medicine; History; Science
KEYWORDS: andrewgehrke; blindness; business; cryptobiology; deafness; dna; genes; genome; godsgravesglyphs; health; helixmakemineadouble; immortality; longevity; mansisrivastava; regeneration; science; spinalcord
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To: Moonman62

I needed one 30 years ago!................


21 posted on 03/15/2019 6:51:36 AM PDT by Red Badger (We are headed for a Civil War. It won't be nice like the last one....................)
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To: Cvengr

Rofl

Oh wait, you are serious arent you? :)

It’s a free country and that’s why we love it!


22 posted on 03/15/2019 7:14:41 AM PDT by dp0622 (The Left should know if.. Trump is kicked out of office, it is WAR!)
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To: Red Badger

No obstacles that a little gene splicing can’t fix/s


23 posted on 03/15/2019 7:19:34 AM PDT by Mariner (War Criminal #18)
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To: Cvengr

“FWIW, the same group of occultic studies into genetics and secreting away of giants from archeology and reportedly war zones, is also associated with Nephilim and attempts to resurrect demons.”

What is your source?


24 posted on 03/15/2019 7:21:49 AM PDT by Mariner (War Criminal #18)
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To: Mariner

Now, all they have to do is check the Human genome for those same sequences. .....................


25 posted on 03/15/2019 7:24:25 AM PDT by Red Badger (We are headed for a Civil War. It won't be nice like the last one....................)
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To: Red Badger
Just a few years ago, the talk was about "junk" DNA and now "non coding" DNA.

This sounds like the script from a ST Voyager episode, where a retrovirus (and probably a transporter accident) de-evolved members of the bridge crew.

Do you want ants to wipe out our species? Because this how you wipe out our species.

26 posted on 03/15/2019 7:25:50 AM PDT by NativeSon ( Grease the floor with Crisco when I dance the Disco)
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To: Red Badger

LOL. I could use one now, but I think in the future it’s going to be a life or death issue.


27 posted on 03/15/2019 7:29:06 AM PDT by Moonman62 (Facts are racist.)
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To: Red Badger
Other animals take the process even further. Planarian worms, jellyfish, and sea anemones can actually regenerate their bodies after being cut in half.

I knew a guy who was head-on side-swiped by a truck when riding his motorcycle.

It sheared off the entire left half of his body.

He's all right now...

28 posted on 03/15/2019 7:34:01 AM PDT by null and void (If socialism is so grand, why are Guatemalans coming here instead of going to Venezuela?)
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To: null and void

I see what you did there..........................


29 posted on 03/15/2019 7:36:45 AM PDT by Red Badger (We are headed for a Civil War. It won't be nice like the last one....................)
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To: Cvengr

These days intent is always suspect.


30 posted on 03/15/2019 7:36:49 AM PDT by null and void (If socialism is so grand, why are Guatemalans coming here instead of going to Venezuela?)
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To: Red Badger
Sorry, Sorry, Sorry, Sorry, Sorry, Sorry, Sorry,
31 posted on 03/15/2019 7:38:16 AM PDT by null and void (If socialism is so grand, why are Guatemalans coming here instead of going to Venezuela?)
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To: Moonman62

If this technology ever get applied to humans, the effects on the economy would be unimaginable.

Imagine if you could do every kind of vice or dangerous behavior and just regen a new body when you had worn yours out or damaged it to the point of being unuseable.................


32 posted on 03/15/2019 7:40:52 AM PDT by Red Badger (We are headed for a Civil War. It won't be nice like the last one....................)
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To: Red Badger

Now would be good...


33 posted on 03/15/2019 7:41:48 AM PDT by null and void (If socialism is so grand, why are Guatemalans coming here instead of going to Venezuela?)
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To: Cvengr

Why are you spreading this nonsense?

Are you insane?

Or something else?


34 posted on 03/15/2019 7:42:03 AM PDT by ifinnegan (Democrats kill babies and harvest their organs to sell)
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To: NativeSon
Just a few years ago, the talk was about "junk" DNA and now "non coding" DNA.

One of the hard truths of evolutionary studies. What was useless yesterday becomes super important today, but the theory is still good.

Vestigial organs used to be touted as proof of evolutionary change, and were a main component of biology textbooks for many years. Then all of the vestigial organs were found out to be doing some very important things and were NOT vestigial. However, nobody ever re-looked the theory once the supports were knocked out, because the theory is more important than its sum parts.
35 posted on 03/15/2019 7:52:29 AM PDT by wbarmy (I chose to be a sheepdog once I saw what happens to the sheep.)
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To: ClearCase_guy

Turning Heathen Liberals into the Gods they think they are.


36 posted on 03/15/2019 7:54:49 AM PDT by carmen2017
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To: ifinnegan
I've heard reports of odd things in Iraq, a passenger in a car with tapetum, the driver nearly too terrified to talk to the GIs at the checkpoint, a huge 'man' in a no-go zone carrying a cow, and literally walking away from a .50 cal hit, and a few other such stories.

Are they true? Beats me, but the reports are there.

And there is no shortage of reports of non-human entities in the Bible, and other cultures' holly books as well. Do you doubt the Bible? (This agnostic asks...)

There are scores of giants in Native American lore. Are they all lying? What about the giant skeletons found in the Lovelock caves in Nevada? (Two rows of teeth, is that human?)

Every culture has demons. It seems either we as a species met genuine evil big creatures, or something in our DNA makes every culture imagine it. What survival benefit would this have as a fantasy to preserve in in our shared genome?

Are you absolutely certain it's nonsense?

An earlier generation was absolutely certain that the reports of the inferior people in Africa of a giant ape was nothing more than the deluded tribal fantasies of primitive near sub-human superstitious ignorant savages.

Then 'credible' Europeans saw gorillas and brought back remains...

37 posted on 03/15/2019 8:01:02 AM PDT by null and void (If socialism is so grand, why are Guatemalans coming here instead of going to Venezuela?)
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To: Red Badger

My undergrad advisor was involved in this exact type of research 40 years ago. He was working with red spotted newts. They can grow legs back after they would be amputated. As I loved newts, even as a little kid, some of the extra newts found their way into my own aquarium, gifts from his graduate students. I also did a senior high school science project on the newts’ shedding of their skin and what triggered it, with this professor as my advisor. Later, he became my college undergrad advisor. This current research uses technology that was not available to my advisor at that time. Many labs have been working on regeneration for years. I just wanted folks to know that this research is not a new idea, although it uses different organisms and different techniques.


38 posted on 03/15/2019 8:16:00 AM PDT by EinNYC
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To: wbarmy
I have no doubt about the importance of the theory or in this case, the study. The development of our knowledge & capabilities within biological sciences and genetics is staggering to consider.

I do have more than a casual concern that a lab with the tools will presumptively move on what is currently understood. And tools of the trade are more readily available now.

A century ago, a poorly constructed hypothesis or incomplete 'theory' was an embarrassment. Today? CRISPR

39 posted on 03/15/2019 8:19:14 AM PDT by NativeSon ( Grease the floor with Crisco when I dance the Disco)
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To: null and void

Two things.

One, what you addressed. Is this cryptozoology, weird phenomen, etc...real?

That’s a fair question and in my opinion the reports and beliefs in these things upon examination is nonsense.

Two, what this has to do with studies of biological properties of worms.

This second one makes zero sense.

And, I think there is a three. It always ends up being anti-Christian.


40 posted on 03/15/2019 8:24:07 AM PDT by ifinnegan (Democrats kill babies and harvest their organs to sell)
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