"What Makes Us Human? The Answer May Be Found in Overlooked DNA"

Well…this may be a little more exciting than the other recent “junk DNA” thread.

“Instead of studying living humans and chimpanzees, we used stem cells grown in a lab. The stem cells were reprogrammed from skin cells by our partners in Germany, the USA and Japan. Then we examined the stem cells that we had developed into brain cells”, explains Johan Jakobsson, professor of neuroscience at Lund University, who led the study.

Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways, which appears to play a considerable role in the development of our brains.

“The part of our DNA identified as different was unexpected. It was a so-called structural variant of DNA that were previously called “junk DNA”, a long repetitive DNA string which has long been deemed to have no function. Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are – which only makes up about two percent of our entire DNA – and examined the proteins themselves to find examples of differences.

The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18 . ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis -acting structural variation establishes a regulatory network that affects human brain evolution.

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The new findings thus indicate that the differences appear to lie outside the protein-coding genes in what has been labelled as “junk DNA”, which was thought to have no function and which constitutes the majority of our DNA.

Why do people keep saying this obviously wrong thing?

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The lay article is even worse than the other.

  1. Title: if the DNA is “overlooked,” why did the researchers find it?

  2. “The new findings thus indicate that the differences appear to lie outside the protein-coding genes…” The lay author is falsely conflating “junk DNA” with noncoding DNA.

  3. “…in what has been labelled as “junk DNA”…” We don’t just label. DNA that has no known function is labeled that way. Note that creationist researchers aren’t doing this work.

  4. “Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are – which only makes up about two percent of our entire DNA – and examined the proteins themselves to find examples of differences.” That’s completely false.

We don’t overlook it and we treat the label “junk” as provisional. We fully expect to find function in a tiny fraction of it. That’s why the researchers didn’t overlook those repeats.

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Disagree. It’s not DNA that has no known function. It’s DNA that we have good reason to believe has no function, notably DNA whose sequence is not conserved. Conserved DNA without known function would never be considered junk.

Now of course it comes as no surprise that many of the relevant differences between humans and chimps are in regulatory sequences rather than protein-coding sequences.

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Fair enough.

It’s a quote from the paper’s author. He’s on Twitter. Someone want to ask him?

https://twitter.com/JakobssonLab?t=wMmNhrZHzoDsBk5QzFMrOA&s=09

Then why is it that the researchers who are interested in getting recognition for their work keep mentioning junk DNA? He also seemed surprised at the results in some of the quotes from the article.

And what does this do for @swamidass explanation for why evolution is true based on math, if they keep finding these kinds of differences of function in the non-coding DNA between us and great apes?

What makes us human? This is entirely a matter of human social convention.

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It does nothing for or against that explanation. Why would you think it relevant?

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Actually the bit I quoted was not from the paper’s author, it was from the author of the release. The original author was quoted as saying

It was a so-called structural variant of DNA that were previously called “junk DNA”, a long repetitive DNA string which has long been deemed to have no function.

Which is also wrong. Calling something junk is not the same as determining it to have no function.

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Ook!!!

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I see that I looked at the wrong section. But his quote is not necessarily misleading, as “deemed” could just be the general understanding, rather than a determination.

One website disagrees with you.

All these definitions seems to disagree with you. [Edit: I forgot this website link initially]

It seems like popular use is it’s junk by default until someone finds a function.

I think I’m just confused. :joy: It happens a lot. Apologies @swamidass

But does anyone think the science is cool?

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There is much misinformation on the web. That one was especially bad. I suggest avoiding that web site, if that page is any guide to accuracy.

That’s not actually what even the definition you cite says. I suppose it depends on just what “no apparent function” means.

It’s a little bit cool. It’s just that the hype around it isn’t.

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No, it’s junk if it’s not conserved and has no known function.

Somewhat, but waaaaay overhyped. The fact that it waspublished in Cell Stem Cell, not Cell, tells you that editors and peer reviewers agree that it is only somewhat cool.

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Cell Stem Cell makes me think of Duck-Duck-Goose. Or, of course, of Cell, Eggs, Sausage and Cell.

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It is cool for reasons that underline how wrong the article’s implications about junk DNA are.

The reason more work has been done with coding regions is because they represent regions of large effect. Break a protein and something big happens, which is nice because it is easy to see and understand. But break a regulatory region, and the impact is likely to be very small. Also, you may not actually ‘break’ it, since regulatory regions operate more on motifs than specific sequences meaning changes are likely to modulate rather than stop the regulation in question. And when you start talking about trans-acting or otherwise highly distal regulation, the exact type of regulatory element you expect to find in junk regions, the effect sizes tend to be extremely small.

But again, smaller effects are harder to study, and historically that has meant ‘almost impossible to study’. So while people have always expected there to be small bits of function scattered throughout, actually finding them has been outside the scope of the available techniques. But now we have more powerful methods for both producing and analyzing data, and so we are finding these things. Rather than ‘debunking junk DNA!’, these studies are confirming what has always been said about junk DNA!

But that doesn’t sound as interesting, so people say silly things.

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What is considered “hype” here?

It had a review date and the other page included definitions from medical dictionaries even though they weren’t recent. So if your definition is the accepted one, then cite a source. But if it’s not in the literature then some science org ought to propose a new accepted definition.

I was defending you. :sweat_smile:

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Not to mention Spam, Spam, Spam, eggs, sausage, Cell, Stem Cell, and Spam.

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The part about nobody previously looking at or thinking about non-coding DNA and the part about junk DNA being a myth.

Here, read this. To quote:

If you read the whole article it might be a useful corrective for the silly web sites you’re looking at.

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“Cell, eggs, sausage and cell 'asn’t got much cell in it.”

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Blockquote differences appear to lie outside the protein-coding genes in what has been labelled as “junk DNA”,

What is wrong with these people? I like how Dan Graur put it.

My problem is that junk DNA does not equal noncoding or nontranscribed DNA, and I am sort of sick to see junk DNA being buried , dismissed , rendered obsolete , eulogized , and killed twice a week.

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