Scientists are redesigning bacteria like these to “speak” a new language.

All living things pretty much use the same language to read their genes. That is about to change.

Scientists in Boston are close to teaching a strain of bacteria a new dialect of the genetic code. In combination with some work done by a different group in 2010, we are now getting to the point where we can actually think about (re)designing life. Which is a big step from what we have been able to do up until now.

The genetic engineering we have done in the past has been pretty crude. We have mostly added pre-existing genes to cells to give the cells new properties or to have the cells make something for us.

So we add a human gene to bacteria so they will make insulin for us. Or we add a gene from bacteria to a plant to make the plant resistant to an herbicide like Round Up. Or we even add two genes to cause rice to make vitamin A like in golden rice.

Now we aren’t always this unsophisticated. We have managed to do some pretty elegant things with genes in mice. There we have tinkered with mouse genes to slightly change how they work or to control how they are expressed.

But these new experiments are different. This is changing the language of life so we can make a living thing do things nothing living has yet been able to do. Maybe this is even the start of intelligent design…

A big reason this is all possible is because nature has given us a very simple template to work with. Not only does the genetic code have just four letters and 64, three letter words, but many of its words also have the same meaning. It is this last point that has allowed researchers to futz with the code.

The researchers plan to teach bacteria a new language by co-opting one of the words in the genetic code and giving it a new meaning. There are two things scientists need to do to make this happen.

The first is to replace all instances of one word in the bacteria’s genes with an equivalent word. Now the bacteria’s genes all still code for all the same things but a word has been freed up so it can be given a new meaning.

The second step is to redefine the replaced word. This will probably be done by mutating the cell’s reading machinery using some pretty well established genetic techniques.

Church’s group has nearly finished the first step. They managed to create four strains of bacteria each with ¼ of all 314 instances of TAG changed to TAA. They are now in the process of combining these four strains in such a way to generate a single strain with no functional TAG’s. After this first step is done (which should be soon), this group of researchers will be ready to teach these bacteria a new language.

An easy first thing they can do is to change the definition of the TAG so it means the same thing as one of the other words. So the TAG will no longer mean STOP but instead will mean Met or Lys or some other amino acid. (The genetic words or codons really just tell a cell which amino acid to put where in a protein.)

Done correctly, this would probably make the bacteria immune to viral infection.* Which would be a boon for the biotech industry as it loses millions of dollars every year because of infected bacterial strains.

This is pretty pedestrian stuff though. The cool thing will be when they redefine TAG as a word that isn’t already in the genetic code. Then we’ll be able to easily create different proteins with properties useful as medicines, industrial enzymes or who knows what else. At least that is the hope.

And this is just one word. There are another 30-40 codons that may be able to be freed up and given new meanings as well.

We are stepping into a whole new area of research. We are retraining life to do what we want. Let’s hope we know what we’re doing…

*This is because viruses use a cell’s machinery to read its own genes. If the machinery changes, the virus will misread its own genes and die.

Mono Lake, the source of the bacteria that can incorporate arsenic, rather than the usual phosphorus, into its DNA.

Mono Lake is on the east side of the Sierra Nevada Mountains, about 300 miles by car from San Francisco. It is an amazing landscape; the lake is set against the backdrop of the snow-capped mountains. There are crispy shrubs nearby, but no trees. Crusty white towers, called tufas, rise up from the water.

The water in the lake is snowmelt and rainwater runoff from the mountains. It enters the lake via streams. But the lake is a closed basin and has no drainage—water can only leave by evaporation. The water evaporates, but the salts and minerals, like arsenic, are left behind. As a result, the lake is very salty—twice as salty as the ocean—and is very alkaline, or basic.

That super-salty water may not seem very hospitable, but in fact the lake is full of life. In addition to the now-famous bacteria, the lake is home to brine shrimp and the larvae of alkaline flies. During the summer, the brine shrimp number in the trillions. They feed on algae that grow green at the lake’s surface. The brine shrimp are food for the two million migratory birds that stop at Mono Lake to feed each year, and the nesting populations of California Gulls and Snowy Plovers.

In addition to its cool geology and important role in North American bird ecology, Mono Lake is at the center of a water supply saga. Water levels in the lake were historically much higher. To get an idea of previous water levels, take a look at the tufas. They were formed while underwater. They’re made of calcium carbonate, which precipitated as fresh water bubbled up from the bottom of the lake. Thousands of years ago, the lake was as much as 900 feet deep, perhaps covering parts of Utah and Nevada. In recent history, the lake was about 170 feet deep.

Beginning in the late 1800s, the freshwater streams that fed the lake were diverted by settlers so they could irrigate their farms. The water level started dropping. In 1941, four of the five streams that flowed into Mono Lake were diverted to the Los Angeles Aqueduct. Supplying the growing city of Los Angeles with water involved intrigue and duplicity and scandal, which were well documented in the book Cadillac Desert. Between 1941 and 1982, because of the reduced freshwater input, the water level in Mono Lake dropped by 45 feet.

The drop in water level was bad for the migratory and resident birds, particularly the California Gulls, which nested on islands in the lake. As water evaporated, some islands become connected to the shore. The birds were no longer protected from roaming coyotes. And, more exposed shoreline meant that the wind kicked up alkaline dust storms. In addition the lake got saltier—at one point it was nearly three times as salty as the ocean.

In response to these changes, the Mono Lake Committee, the National Audubon Society, and other conservation groups have begun to restore Mono Lake. It is now mandated that more water flow into the lake, and the water level has started to rise. The habitats and ecological processes of the lake are recovering. Additional discoveries, like the bacteria that can use arsenic to make its DNA, will hopefully rise out of Mono Lake in the future.

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Scanning electron microscope image of the arsenic-loving bacteria GFAJ-1. (Credit: AAAS/Science)

Reported for KQEDnews.org.

A Bay Area biochemist has found a new strain of bacteria living in the briny shores of Mono Lake that can eat and thrive on arsenic, a substance highly toxic to most organisms. The discovery may lead to a significant shift in how scientists search for extraterrestrial life.

“All life that we know of requires carbon, hydrogen, oxygen, nitrogen, sulfur and phosphorus,” said Felisa Wolfe-Simon, the lead author of the study and a NASA Astrobiology Research Fellow in residence at the U.S. Geological Survey in Menlo Park. “We discovered an organism that can substitute one element for another,” she added.

Those six major elements comprise the building blocks of key components of living cells, such as DNA, RNA and proteins – the molecular switches which power the cells and instruct them to perform tasks critical for cellular growth and survival. Researchers know of no other microbe that can consume arsenic let alone substitute it for phosphorus, thereby expanding the definition of what constitutes life on Earth and elsewhere in the universe.

“As someone who regularly gives lectures in which I state, ‘every living thing uses phosphorus to build its DNA’, the idea that I’m sitting here today discussing the possibility that that’s not true is quite shocking,” said James Elser, a professor at Arizona State University who participated in a NASA teleconference convened today to discuss the findings.

The discovery of the arsenic-loving microbe also “opens new doors” to explore what life may look like in other reaches of the solar system, on environments such as Mars or the moons of Jupiter and Saturn that have previously been thought to be too cold and harsh to support life.

Felicia Wolfe-Simon of the NASA Ames Research Center and USGS collects samples from a sediment core extracted from the shores of Mono Lake in eastern California. (Credit: Henry Bortman)

“We still don’t know everything there is to know about what might make a habitable environment on another planet or a satellite of another planet,” said Pamela Conrad, an astrobiologist at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. “Perhaps arsenic is not an essential component for habitability or life but it may be one that can be tolerated and it opens our perspective to try and understand what other potential components may be tolerated or perhaps even essential that we presently haven’t thought of,” she added.

A paper describing the finding appears in this week’s edition of the journal Science Express.

But before the embargo on the paper was lifted on Thursday, a flurry of speculation was set off earlier in the week that NASA had discovered proof of alien life, fueled by an ambiguous press release issued by NASA on Monday which trumpeted “an astrobiology finding that will impact the search for evidence of extraterrestrial life.” In fact, the embargo was lifted roughly two hours earlier than planned because reports of the finding, some of them erroneous, were already beginning to appear online in publications like The Huffington Post and the Guardian.

At the end of NASA’s Thursday teleconference, Mary Voytek, director of the Astrobiology Program at NASA headquarters in Washington, D.C. responded to a question from a USA Today journalist about the disappointment felt by its readers that in fact, NASA would not be pulling E.T out of a hat.

“I guess what I would say is that while being able to announce the discovery of an extra-terrestrial would be an incredible announcement, from our perspective, this is a phenomenal finding. It will require some paragraphs in textbooks to be rewritten,” said Voytek. “It will fundamentally change how we define life and how we look for it, maybe we’ll be able to find E.T. now because we’ve got more information about what we might be looking for,” she added.

The research team, led by Wolfe-Simon, discovered the new strain of bacteria, GFAJ-1, in muddy sediment cores extracted from the shores of Mono Lake, located in eastern California, near the Sierra Nevada mountains. The 70 square-mile inland lake is highly salty and alkaline with high concentrations of naturally-occurring arsenic. It has been separated from freshwater for 50 years and teems with brine shrimp and algae. It also serves as a major stop-over point for migratory birds.

Wolfe-Simon chose to investigate how GFAJ-1 responded to arsenic because of the toxic compound’s chemical similarity to phosphorus. She pointed out that arsenic lies just below phosphorus on the periodic table and that their atoms are roughly the same in size. But arsenic is highly toxic to most living organisms because it disrupts metabolic pathways in the cells which take up arsenic readily, given its chemical similarity to phosphorus.

So Wolfe-Simon took the muddy samples containing the bacteria and grew them in petri dishes in a watery solution containing sugar and high levels of arsenic, while reducing the amount of phosphate salt the bacteria were fed. Eventually, the bacteria were fed only a diet of arsenic.

“It grew and it thrived, and this was amazing. Nothing should have grown,” said Simon.

In just six days, the bacteria multiplied twenty-fold as it wolfed down the arsenic.

Simon and her colleagues used radiolabeled arsenate, a form of arsenic, to track the movement of arsenic inside the bacteria. With the aid of additional laboratory techniques, they found that the bacteria’s cellular machinery of lipids, proteins, even its DNA, were now made up of arsenic. So the bacteria were able to fully substitute phosphorus, which provides the chemical backbone of DNA, for arsenic and still function and grow just fine.

Mono Lake, located in eastern California, next to the Sierra Nevada mountains, is highly saline and has high concentrations of arsenic. (Credit: Henry Bortman)

"We know that some microbes can breathe arsenic, but what we've found is a microbe doing something new — building parts of itself out of arsenic," said Wolfe-Simon.

And according to Professor Elser at Arizona State University, the discovery of a microbe that thrives on arsenic may have value beyond the lab and academic papers. Elser mused on the possibility of using GFAJ-1 to clean up naturally-occurring arsenic, which can pollute groundwater and lead to failure of organs such as the kidneys and liver if ingested.

Then there’s the burgeoning field of biofuels, the next generation of which include algae. But algae and other plants being cultivated for renewable fuels require phosphorus to grow.

“So what if someone was clever enough to be able to develop a bioenergy creature, a microorganism, based on this metabolism that doesn’t need phosphorus, so you don’t need to drain the fertilizer supply in order to solve the bioenergy problem,” said Elser. “It’s pretty exciting to think about the possibility of organisms that may be able to live without phosphorous,” he added.

For Felisa Wolfe-Simon, the discovery of the arsenic-loving bacteria is an important milestone in astrobiology, a discipline which combines chemistry, astronomy, biology and other sciences to understand the evolution of life and the future of life – on Earth and beyond.

“We’ve cracked open the door to what’s possible for life elsewhere in the universe and that’s profound and to understand how life has formed and where life is going,” she said. “And what else might we find, what else might we want to look for?”

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Life was easier back before I produced this piece. Now everywhere I look and everything I touch seems to be made of plastic.

I don’t know why I didn’t think about plastic before I produced this story about plastic from around the world that’s gathering and collecting in the Pacific Ocean. But now, everywhere I look and everything I touch seems to be made of plastic: this keyboard, pen, desk, the monitor in front of me, my water bottle, the phone to the left of me, the stacks of video tapes in plastic containers to the right, even the plastic office chair holding me up. But I’m not just struck by the fact that everything’s made of petroleum products. I’m stunned by the fact that I knew all the time that I was surrounded by plastic, but I’d found ways to ignore it, accept it and live with it.

Life was easier back before I did this piece. I didn’t think of albatross stomachs when I saw cigarette lighters for sale. I didn’t have to worry what to do with the plastic lid on the recycled paper cup after I drank my fair trade organic coffee. I didn’t get strange looks from the corner sandwich shop lady until I recently removed a lunch from the plastic bag she provided. I had to explain to her why I didn’t want the plastic bag she so carefully and skillfully packed with my chicken salad sandwich, cheddar cheese chips and juice (in an actual glass bottle).

I told her how plastic doesn’t go away for centuries, how it breaks down into smaller and smaller pieces, even nano-sized particles. I went on about how it could get into the food chain. She didn’t have an answer when I asked her if she knew what we’re doing to the ocean and the planet and our children. Plastic was the enemy and it was everywhere!

I knew I was getting carried away. But then I started thinking maybe I should get carried away. Maybe we all should get carried away, you know, talk about it, get informed about it, get angry about it, write our senators and members of Congress. But being a TV producer who’s always faced with making difficult cuts in the edit room, I knew when less was more. So I chilled out, gave her what I owed for the food and time and left a hefty tip, and started to leave. Her smile made me pause. She thanked me for telling her all about plastic. She said she’d speak to the owner about replacing the plastic bags.

Watch the Plastic in the Pacific television story online.

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Often at the California Academy of Sciences, you will see docents out on the floor of the museum with an example from our live animal collection.

You've probably heard of this bacteria before, as an unpleasant bug that sometimes finds its way into high-protein foods such as meat, fish, and eggs. It is also naturally found on and in many reptiles, and does not usually make the animals sick, but if passed to humans– particularly young children, the elderly and infirm — it can cause a serious infection called Salmonellosis.

But selecting the right anti-microbial was not as easy a choice as we thought it would be.

Food and Drug Administration published reports question the use of antibacterial soap and hand sanitizers, saying that it found no medical studies that showed a link between a specific consumer antibacterial product and a decline in infection rates. Plus, regular soap kills 90% of bacteria and leaves little impact on the environment.

Additionally, anti-bacterial products like Purell use synthetic polymers known as Triclocarban and triclosan to kill off bacteria. Triclosan is known to promote the growth of resistant bacteria, including E. coli, and both pose environmental toxicity risks; after washing your hands or washing the dishes they can get into the waste water system. Because they do not break down or get filtered out during waste water treatment, up to 75 percent of the original amount gets into the Bay. Once in the environment, these products have been known to disrupt the health of marine life and other wildlife.

So Academy scientists went in search of an alternative product that does not contain the above 2 agents, and has recommended Vionex Antimicrobial Soap for our public programs. Commonly used in the medical, dental, and law enforcement industries, Vionex uses a different antimicrobial agent called PCMX, or parachlorometaxylenol, which is considered significantly less toxic to humans and other mammals that Triclocarban and Triclosan.

What you can do at home

Even if you are not handling reptiles daily like we are, you can take action to reduce exposure to toxic anti-microbials. Whenever possible avoid products that are labeled “anti-bacterial.” Products that are likely to be anti-bacterial are most hand-sanitizers, hand wipes, cleaning products, and dishwasher detergent. If you must use hand-sanitizers, consider natural ones such as Hand-Sanz (found at Whole Food or Bristol Farms).

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UCSF biologist Jeff Tabor holds up an ecoli culture designed to display the shape of a squid.

Synthetic biology portends big changes in our lives by ushering in a dizzying array of applications in everything from medicine to biofuels, environmental remediation to agriculture. Though many of these applications haven’t yet come on line, researchers are hard at work to synthesize new drugs and devices made from genetic parts.

For example, there’s an enzyme that exists in plants which makes methyl halides, a molecule which can be catalytically converted into gasoline and other chemicals. Imagine if you could put this enzyme-making gene into yeast, then you could brew the yeast to churn out the methyl halides and after some optimization of the production pathway, you could scale up production to pump out this carbon neutral gasoline precursor for use in today’s automobiles. This is the idea behind an innovative biofuels project that has taken off in the lab of Chris Voigt at UCSF’s School of Pharmacy.

Voigt and his team surveyed the genetic database for the presence of the gene that encodes for the enzyme that makes methyl halides. Lo and behold, the gene exists in plants as diverse as ice plant, which dots the northern California coast, bok choy and pinot noir grapes. After building a library of about 100 enzymes from these diverse plants, the researchers had to determine which of these would function best in the yeast. They zeroed in on an enzyme from ice plant and then used the tool of DNA synthesis to translate the gene for the enzyme that makes methyl halides into something that would work in yeast.

The remarkable thing about this project is that the researchers never actually touched any of the plants. They simply “Googled” a genetic database to find all the genes out there in plants that produce the enzyme that makes methyl halides. As Professor Voigt says, “it’s incredible that synthetic biology is something that could really unlock the potential of using organisms in order to produce fuels.”

Watch the video made by the Voigt Lab demonstrating the combustible property of their synthetically derived methyl halides:

QUEST on KQED Public Media. Video courtesy of
Prof. Chris Voigt, UCSF School of Pharmacy

Watch the Decoding Synthetic Biology television story online.

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The swine flu virus, up close (and colorized!)
Credit: C. S. Goldsmith and A. Balish, CDC

Swine Flu has been blanketing the news as of late. On April 29th, the Centers for Disease Control and Prevention (CDC) reported the first US fatality occurring in Texas. The CDC has determined that this swine influenza A(H1N1) virus is contagious and spreading from human to human. Yet at this time, they do not know how easily the virus spreads between people. At our museum, we have taken this very seriously and staff has been asked to stay home if symptoms arise.

CDC is recommending that those who come down with flu-like symptoms stay home from work in order to decrease the rate of infection. The Swine Flu is a viral infection rather than a bacterial infection, which makes it harder to treat. Much of the care for viruses is preventive; viruses are hard to treat after they have entered a living host.

Many people do not know the difference between a viral infection and a bacterial one and consider them interchangeable. Yet they are quite different. Viruses are sub-microscopic particles ranging in size from 20 to 300 nanometers (about 1000 times smaller than the width of a human hair). Viruses must have a living host to function. They remain dormant until they infect a living cell. Within a cell, they then change the genetic material of the cell to replicate the virus. AIDS and Influenza are both created by this process of taking over the normal function of a cell in order to replicate viral cells.

Bacteria do not take over cells. Bacteria are much larger than viruses, usually 10 to 100 times bigger than a virus. Their shapes include curved rods, spheres, rods and spirals. They are known as intercellular organisms because they live between cells. All viruses are harmful to the host because they alter cells, but bacteria can be beneficial (like the species that live in our guts and help us digest our food).

Harmful bacteria in the body create infections like Strep throat or Small Pox. Bacteria can grow and reproduce in both living and non-living environments. Antibiotics are used to treat harmful bacterial growth and infection in the body. Antibiotics; however, are ineffectual against treating viruses.

Because the Swine Flu is a virally spread disease, it is even more important to practice prevention. The CDC sees this disease being spread like a common flu – mainly from person to person through coughing or sneezing by people with influenza. People can also become infected by touching something with flu viruses on it and then touching their mouth or nose. Taking simple precautions like washing your hands and covering your mouth when sneezing is effective prevention. Working in a museum,we take this extra seriously considering how often we come in contact with lots of people and their germs. Many of my co-workers, myself included, have hand sanitizer at our desks, wash our hands often, and carry tissues. It is a simple way to combat an evasive illness.

For more about how to protect yourself from swine flu, check out this podcast from the CDC.

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Scientists gather samples on the ocean floor.
Credit: Roger Linington.

What's different about the work being done at the UC Santa Cruz Chemical Screening Center is that it a) looks to a largely unexplored medical resource: the ocean, and b) uses robots, rather than "forlorn-looking grad students" (to quote Center director Scott Lokey) to run the tests.

Here's a video I shot of one of those robots in action, with Lokey narrating.

One thing that didn't make it into the piece is that these researchers — including Lokey and Roger Linington — aren't just studying every disease they can think of. They focus on the diseases that commercial drug companies tend to neglect because there's so little profit in treating them – things like African sleeping sickness and cholera. So far, they're seeing progress on both, as well as breast cancer.

Listen to the Medicine from the Ocean Floor radio report online and check out images from this story in an online slideshow.

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There is an awful lot of DNA stuffed into every cell.

Let's start out with people. Each human cell has around 6 feet of DNA. Let's say each human has around 10 trillion cells (this is actually a low ball estimate). This would mean that each person has around 60 trillion feet or around 10 billion miles of DNA inside of them.

The Earth is about 93 million miles away from the sun. So your DNA could stretch to the sun and back 61 times. That is one person’s DNA.

The best estimate I could find of the world’s population of people is around 6.7 billion. When we multiply 10 billion miles of DNA by 6.7 billion, we end up with, well, a really big number. Something like 6.7 X 10¹⁹ or 67 quintillion miles. That is too big a number so let’s convert this to light years.

A light year is around 6 X 10¹² miles. So all human DNA would stretch 11.2 million light years. The closest star to Earth (besides the sun) is around 4.2 light years. So we shoot way past that! The Andromeda galaxy is about 2.5 million light years away from us so human DNA could stretch there and back two or three times.

What if we add the rest of the DNA on the planet? It would obviously be much farther but it is hard to calculate because we don’t know how many plants, animals, bacteria, fungi, etc. there are on the planet. We also don’t have detailed information about every species on Earth.

Let's add bacteria to the mix. I decided on this because we know how many cells are in a bacterium—one.

One number I saw was that there are 5 X 10³⁰ bacteria on Earth. Bacterial DNA tends to be a lot smaller than human DNA so there will be less of it per cell. Let's say on average there is 4 million base pairs of DNA/bacterium (this number could be off by a very lot). This translates to around .05 inch of DNA per bacterium which means you need to scrape together around 1.3 million bacteria to get a mile of DNA. So all the bacteria in the world have about 3.5 X 10²⁴ miles of DNA.

How far is 3.5 X 10²⁴ miles of DNA? Well, it is about 640 billion light years of DNA. The end of the observable Universe is about 14 billion light years away. So if we stretched out bacterial DNA it would go to the end of the Universe and back around 23 times. Of course it would be incredibly thin and so actually doesn't take up much space in the Universe.

So that's just human and bacterial DNA. (Well, mostly bacterial since human is so piddly in comparison.) I haven't added all of the rest of the DNA out there. I'll leave that to you.

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This photomicrograph shows Cyanobacteria (green) found
in a common pond. Image source: Wayne Lanier

A billion years ago or so, mitochondria were free living bacteria. Then our ancestors hijacked them and now they do our bidding. And mitochondria aren't the only cells that got hijacked. So did the chloroplast’s ancestors.

Chloroplasts are the part of a plant cell that turns sunshine into sugar. Every green plant that we’ve looked at has them. And chloroplasts were almost certainly once free living cyanobacteria.

Both mitochondria and chloroplasts still have many bacterial qualities including having their own DNA. But they don't have a lot of their old DNA left. Most of it has migrated to where the rest of our DNA is kept—the nucleus. Or at least that's the theory.

Do scientists have any proof that DNA can move in a cell from compartment to compartment? As a matter of fact they do. At least with the chloroplast.

Scientists used their ability to put DNA specifically into a chloroplast or mitochondrion to design an experiment to look for cells where DNA had migrated. What they did was put some DNA into a chloroplast that could only be read in the nucleus. (Remember, chloroplasts and mitochondria are different enough that nuclear DNA doesn't work there and vice versa.)

The DNA they put in made the plant resistant to a poison IF the DNA could be read. One way the plant could survive was if the DNA they put in the chloroplast ended up moving from there to the nucleus. And it did.

In fact, it was pretty common in their experiment. The DNA moved in something like 1 in 16,000 pollen cells. A rate like this suggests that, for example, different cells on the same leaf might have different amounts of chloroplast DNA in their nuclei.

So DNA can move from the chloroplast to the nucleus. And probably from the mitochondrion to the nucleus too. The evidence is less direct for this but there is plenty of DNA in the nuclei of lots of different plants and animals that looks very mitochondrion-like.

This all fits in with our understanding that DNA is not as stable as a lot of people think. DNA changes between generations and within an organism. Chromosomes can get rearranged, genes copied or deleted, small DNA changes can happen and who knows what else. And these changes are a big part of the motor that drives evolution.

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