Human-plant hybrid cells reveal truth about dark DNA in our genome

Which part of our genome really matters? Some argue that since most of our DNA is active, it must be doing something important. Others say that even random DNA will be very active. This has now been tested by studying human cells containing huge chunks of plant DNA. New scientist can exclusively reveal – and essentially random plant DNA was indeed almost as active as human DNA.

The discovery shows that much of the genome's activity is just noise rather than having any purpose, and thus adds to evidence that much of the human genome is junk.

“A large number can be explained simply by background noise,” says Brett Adey at the University of Auckland in New Zealand. “This seems generally consistent with the idea of ​​junk DNA.”

The main function of DNA is to store the recipes for making proteins, the molecular machines that do almost all the work in cells. DNA recipes are copied to create messenger RNAs, which pass the recipes to ribosomes, the cell's protein factories.

It was originally thought that almost all DNA was made up of recipes for making proteins, but we now know that only 1.2 percent of the human genome codes for proteins. So what should the rest of us do?

Since the 1960s, many biologists have argued that it's mostly trash. Yes, a small percentage of non-protein-coding DNA is really important, and we probably keep opening pieces who have been doing useful things for decades, but such discoveries, they say, will not change the big picture that the vast majority of non-coding DNA is junk.

For example, a 2011 study found that Only about 5 percent of the genome is retained for a long time – evolution doesn't seem to care about the rest. Junk Camp biologists also note that genome sizes vary greatly among species. Why onions need five times more DNA than humansFor example? Why lungfish have 30 times more of them?

But other biologists have focused on whether human DNA does anything—for example, turns into RNA—even if that RNA has no known purpose. In 2012, a large project called ENCODE concluded that more than 80 percent of the human genome was active in this sense and argued that this shows that it is not trash after everything. Some biologists in this camp use the term “dark DNA” to refer to non-coding DNA, the idea is that it is important for reasons we don't yet understand.

In response to ENCODE's 2013 claim. Sean Eddy at Harvard University proposed a random genome project. “Suppose we put a few million bases of completely random synthetic DNA into a human cell and run Project ENCODE on it,” he wrote.

Will we still see all ENCODE actions being heralded as proof of functionality? “I think so,” Eddie concluded.

“You can't draw any conclusions just by measuring activity. And that's the genius of Sean Eddy's random genome idea: what we really need is a baseline,” says Austin Ganleyalso at the University of Auckland. “Without that baseline, everything you're looking at doesn't make sense in terms of choosing between function and garbage.”

However, producing synthetic DNA is expensive. So far the only attempts at a random genome project involved small pieces of DNA no longer than approximately 100,000 base pairs.

But when Ady and Ganley learned that researchers in Japan created hybrid human and plant cells containing 35 million base pairs of watercress DNA (Arabidopsis Taliana), they realized that this could be considered the largest random genome project to date.

Eddie, who was not involved in the study, agrees. Plants and animals descended from a common ancestor at least 1.6 billion years agotherefore, during this time the mutations “effectively randomized” the non-coding DNA into A. Taliana. “Each site mutated several times,” Eddie estimated when asked about this approach.

After initial studies to verify that plant DNA was indeed random as far as human cells were concerned, Adey and Ganley then measured the number of starting points for DNA to RNA conversion per 1000 base pairs of non-coding DNA.

If conversion of DNA to RNA is truly a sign of function, then it is unlikely that any plant DNA should be converted to RNA. In fact, Adey and Ganley found only slightly less activity: the number of start sites per kilobase of noncoding information was about 80 percent higher. A. Taliana DNA versus non-coding human DNA.

In other words, this strongly suggests that almost all of the activity observed by ENCODE is noise.

“This is a great demonstration of how noisy biology is,” says Chris Ponting at the University of Edinburgh in the UK. “The biochemical activity occurring within this [plant] the sequence clearly has no function in the human cell.”

“This very elegant study was needed,” says Dan Graur at the University of Houston, Texas. “It offers even more experimental evidence to confirm what has been obvious for years: most of the human genome is junk. The term 'dark DNA' is laughable nonsense, made up by people with a bad case of physics envy.”

A perfectly designed system would have no noise, Ganley says, but evolution doesn't create perfect designs. AND noise can have benefits. “If you have these imperfect systems that have a lot of noise in them, that noise can actually create interesting things that can then be discovered through selection,” he says.

So far, the team can't explain why human DNA activity was 25 percent higher. “All we can say is that it requires an explanation,” Ganley says.

It's possible that some of the additional RNAs do have functions—that wouldn't change the unhelpful conclusion—but there are other potential explanations. Researchers are now using machine learning to see if they can find ways to distinguish potentially meaningful activity from background noise.

The team plans to publish the results but has not yet written a paper.

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