New Genes | A Science Explainer with Dennis Venema

Stump:

Welcome to Language of God. I’m Jim Stump.

Hoogerwerf:

And I’m Colin Hoogerwerf.

Stump:

So there’s this somewhat recent science story in the news that we’re going to talk about today. When I first came across it, I sent it over to you.

Hoogerwerf:

And I said, “I don’t get why this is exciting.”

Stump:

So we decided to make an episode about this thing you didn’t think was very exciting.

Hoogerwerf:

Yeah, well, the thing is, I understood that some people were excited about it, and I think I wanted to be excited about it, but it was also buried in this layer of complexity that I just couldn’t grasp it. But I thought it’d be a good challenge to try to unbury it a bit and let the excitement out and pass that on to listeners.

Stump:

All right. Here’s a new genre of podcast for us, the Explainer Audio.

Hoogerwerf:

Where an ecologist and a philosopher explain things they were never trained in.

Stump:

I suppose we need some help. This one’s about genetics. So we turned to a good friend of BioLogos, Dennis Venema. He wrote some great articles for us about the basics of evolution back in the early days of BioLogos. He was on the podcast a couple of years ago, right along with Michael Peterson. But in that conversation, we didn’t get him going fully on his real specialty, which is genetics.

Venema:

Well, thanks for the opportunity to get back in the saddle a bit.

Hoogerwerf:

Let’s start with a summary of the study that came out in the Journal Science, right?

Stump:

Right. This is the pinnacle of scientific publication to get something in Science. The title of the article was “Human Gene Linked to Bigger Brains was Born from Seemingly Useless DNA.”

Venema:

Okay, yeah. It was an interesting study for a number of reasons. It’s kind of the confluence of two interesting topics to biologists and also to lay people in general. One of the things of general interest about what it means to be human is just how are we different from other organisms that we’re related to? Of course, a bigger brain, a more heavily folded brain, is something that we’re interested in, and how that came about in our evolutionary history is something that we’re fascinated with, so that’s kind of the one part.

Hoogerwerf:

Okay. There’s two different aspects of this study. We’re going to take them one at a time. One part has to do with how human brains are different than other brains and how they came to be different. Let’s hold onto that. We’ll get back to it.

Venema:

Then the other part of it is, oh, how do new genes come into being? We’re interested, biologists are interested, in how new genetic information comes into existence and the different mechanisms by which it comes into existence.

Stump:

What we’re talking about here is the development of new genes.

Hoogerwerf:

More specifically what scientists call this process De novo gene birth, genes coming from nothing.

Stump:

They’re actually coming from something, that’s what this study is about, it’s just that they’re not coming from the places that we expected them to come.

Hoogerwerf:

Yeah, so after reading this, it was pretty clear that scientists were pretty excited about this. The excitement seems a little bit dependent on having some background knowledge on what a gene actually is, what we expect of them. I’m at least 15 years out of my last cells and genetics class, and even then I was pretty happy to think about genes in this abstract way, just something inside of you that controls what characteristics come out.

Stump:

Right, so we need some vocabulary here. Those characteristics are phenotypes in the scientific language, which is just a fancy word from the Greek for house, something looks or appears. It’s usually contrasted with the genotype, which is the set of genes, the instruction book, according to which our bodies are built.

Hoogerwerf:

But where genes come from wasn’t really ever on my radar.

Stump:

Right. Let’s step back, do some basic cells and genetics biology here.

Hoogerwerf:

Yeah, sounds good. We can probably start with DNA.

Stump:

Which is made up of four different chemicals called nucleotides.

Hoogerwerf:

The As, Cs, Gs, and Ts.

Stump:

Yes, but it’s probably good to point out that our DNA doesn’t actually have letters in it. That’s taking the metaphor of language a little too far. The As, Cs, Gs, and Ts are our symbolic representation of those chemicals that are strung together in DNA.

Hoogerwerf:

The DNA has that double helix structure we often see, two long strands of those nucleotides twisted around each other, and the nucleotides on each strand are linked in pairs, A with T, G with C, and all those strands are coiled up inside the nucleus of every cell in your body. That DNA in the nucleus is then transcribed into RNA segments, which are copies of shorter sections of DNA.

Venema:

The metaphor is we take DNA, a sequence of letters, we transcribe it, we make a copy in the same language, which is what that metaphor transcription’s about, and then that transcript is then taken out of the nucleus of the cell where the DNA is stored, and it goes to what’s called the cytoplasm, the outside of the nucleus.

Hoogerwerf:

There in the cytoplasm, outside of the nucleus, the RNA meets up with a ribosome, at least in most cases, which reads off the letters and organizes some amino acid to form a protein.

Stump:

Right. Then proteins form cells, cells form tissues, tissues form organs, and organs form creatures like us.

Hoogerwerf:

All right. DNA, made of nucleotides, transcribed into RNA in the cell, and then translated into a protein out of the cell by a ribosome. Where does a gene fit into all of this?

Stump:

The simple answer is that a gene is just a section of the DNA that codes for a protein through that process you just described.

Hoogerwerf:

But things are never quite as simple as the simple version are they?

Venema:

Gene is one of those sort of fuzzy concepts in biology, but there are many genes that we know of that are not translated where the function of the gene itself is just the RNA transcript that does the job. Ribosomes, for example, the complex that makes proteins, the enzymatic core of a ribosome is strictly RNA that has enzymatic function. The genes for those components are just used at the RNA level. You don’t have to be made into protein to be considered a gene.

Stump:

Okay, so not every gene goes through that process we just described, but you do have to do something to be a gene.

Hoogerwerf:

Gene is a section of DNA that has some kind of specific function doing something, most of the time it’s making a protein, and genes can be different lengths of nucleotides. I even learned that genes aren’t always exclusive to their places on the DNA.

Venema:

It is possible to have genes overlap and share sequences so sometimes they are kind of nested either within each other, or you can have a gene on one side of the double helix and a gene in the other direction on the other side of the helix. That’s possible too.

Stump:

We start to see more of this fuzziness in genes, but there are also many parts of DNA that don’t correspond with a gene at all.

Venema:

It’s often surprising to non-biologists how little of our DNA is actually made into proteins. It’s on the order of about 2 to 3% that’s actually coding, making proteins in that way. That’s often surprising to people. There’s this huge amount of our DNA that doesn’t seem to be used for this making protein type of function.

Stump:

We’re going to start moving back toward this study and what was so interesting there, but maybe first let’s figure out what the rest of DNA is doing, because to say that a gene is something with a function doesn’t necessarily mean that non-genes aren’t doing anything.

Venema:

The evidence that we have is that a large amount of it does not have a sequence-specific function. In other words, there might be some functionality with the fact that there’s sort of stuff there in broad sense, but that it doesn’t have a sequence specific function. We can see those sequences change over evolutionary time and it not have a significant impact on the organism.

Hoogerwerf:

All right. I think this is helpful. I just want to make sure I’m getting it. Part of the reason we know that at least some of these non-coding sections aren’t important to actually building our bodies is because we have evidence of all kinds of changes happening in those sections of DNA and no changes happening in the creature. Whereas with other parts, the coding parts, if there’s a change there, there’s going to be a change in the creature, a phenotype is affected.

Stump:

Yes. Those sections have been very helpful in determining common ancestry of different species because they can be compared to each other and their differences, which are the mutations that have accumulated in them, those differences let scientists create family tree with a high degree of confidence.

Venema:

But another thing that we found out in the last decade or so is that a large amount of our genome, even though it isn’t made into a protein coding gene, a large amount of it is actually transcribed. Because a large amount of our genome is transcribed into these long RNA copies, it becomes this available pool of things that could potentially become protein coding genes if certain changes came into place, even though these sequences are being transcribed but are not being taken out of the nucleus to where they could be translated into a protein.

Stump:

What we’ve got is a stretch of DNA that seemed for a long time it wasn’t being turned into a protein and not because it wasn’t being transcribed, it was, and not because it didn’t have a good recipe for protein, it did have a good recipe, but because it was stuck in the nucleus and couldn’t pass the recipe onto the chef out in the cytoplasm of the cell?

Hoogerwerf:

Yeah. Okay. I think I’m following here. In the long strands of DNA, a bunch is being made into RNA copies. Some of those copies are leaving the nucleus and turning into proteins, and some of the RNA copies are just stuck in the nucleus, whether or not they have good recipes for proteins. But why can some RNA leave and other RNA is stuck?

Venema:

One of the ways that it can happen is that they lose these signals that are keeping them inside the nucleus. What these researchers were interested in, they looked at a large number of these and did some fun, cool computational analyses, basically to look for things that are features in common for what’s keeping things in the nucleus and what’s allowing them to get out of the nucleus.

Stump:

In all those RNA strands, remember built from nucleotides, there are some specific sequences of nucleotides that become markers to distinguish them.

Venema:

You can kind of think of it as a baggage tag. It’s like, “Okay,” so the cell looks at this baggage tag and says, “Okay, this one stays here.” Then in the absence of that, it’s like, “Oh, okay, we can let it go.” You can think of it as sort of like a baggage tag, a sorting tag.

Stump:

That brings us to our specific sequence that was found in this study. The sequence started as one of these stay here baggage tags, but somewhere along the way, it gained a new baggage tag that let it get out.

Hoogerwerf:

A De novo gene is born.

Venema:

Yeah. It’s something that’s coming into being as a protein coding gene from a non-coding source.

Stump:

As opposed to how we’ve mostly understood our genes to come about, which is through tweaks to already existing genes.

Venema:

Part of the thing that we need to keep in mind is that a lot of the things that make us different from our relatives will be tweaks to existing things, things that we all share, genes that chimpanzees have, that rhesus macaques have, protein coding genes, and finding those tweaks on our lineage, the subtle changes of those genes that also contributed to what makes us human, those are going to be harder to find. These ones are easier to find because they stand out like a sore thumb. Here’s something brand new. Let’s test it and see i.e. where it came from and also what effect it might have.

Stump:

How’s all this sitting with you?

Hoogerwerf:

Good. I think I’m at a place where I understand this aspect of the study, and really what scientists are excited about is simply that we learned about some new way that genetic information comes about. We’ve known about the DNA to RNA to protein process for a long time, and we’ve known that tweaks in those genes are one of the main sources of genetic change over time but it turns out there are other ways that genetic change can come about, and this way turns out to be a lot faster. There’s still a few details that confound me, like how the sequence changed baggage tags and who’s actually checking the baggage tags, but I think it just has to do with the complexity of genetics and maybe also something to do with how small this all is, and probably also that the metaphor only goes so far.

Stump:

Yeah. Well, let’s move on to the next part of the study.

Hoogerwerf:

Right, so the title of this paper is “Human Gene Linked to Bigger Brains was Born from Seemingly Useless DNA.” We’ve dealt with the second part of that title, about how this gene came from something that seemed to not have a function, and probably lots of genes could come about this way, but the particular gene these researchers studied seems to be related to something pretty interesting.

Venema:

I don’t think that this particular mechanism would’ve got on the radar with the public in the same way if it hadn’t been something that was so interesting to us about human uniqueness.

Stump:

One of the things that might distinguish us from other animals is our brains. Before an argument starts about what’s really unique about us, let’s acknowledge that there are a lot of ways to measure brains and none of them are perfect. An obvious measurement is to look just at brain size by weight.

Hoogerwerf:

The biggest, heaviest brain goes to the sperm whale.

Stump:

Or you could look at the total amount of neurons in a brain.

Hoogerwerf:

Winner in that category? The elephant.

Stump:

It’s not too surprising that we don’t win on those measures since whales and elephants are so much bigger than we are. This is where the encephalization quotient is often cited, which is the ratio of brain size to body size. There, ours is really big compared to other animals, but not quite the biggest.

Hoogerwerf:

The biggest turns out to be any guesses? The shrew.

Stump:

You can look at the folding of the brain or the surface area, which is what this study is about.

Hoogerwerf:

Dolphins actually have one of the most complex brains when it comes to surface area and folding. But what’s clear is one simple brain statistic like this isn’t going to tell us why we’re doing podcasts and whales, elephants, shrews, and dolphins aren’t.

Stump:

On the other hand, when we find out that at some point in our evolutionary history a change came along that made our brains more heavily folded, that might be at least part of the story of what has given us cognitive superpowers and made us uniquely unique.

Hoogerwerf:

We’re still saying that?

Stump:

I think we are. I just did.

Venema:

The big takeaway here is that there are going to be a lot of those sort of changes that shifted our lineage towards a more heavily folded brain. It’s all about packing more neurons into that relatively fixed space. Our skull can only be so large because of our biology. We got to fit through a pelvic canal so the way you get smarter with those constraints is you increase the surface area of what’s inside by folding it.

Hoogerwerf:

What the researchers did was they took this gene, they did a bunch of experiments with cell cultures grown in labs or organoids that can simulate what would be happening in the human brain.

Venema:

They can take the gene away and see what happens. They can over-express the gene, they can give those organoids more of that protein than they would normally have and see what the effects are. They can mutate certain aspects of the gene and then put it in and see what its effects are.

Stump:

Then they take it a step further and they actually engineer the gene into mice and watch to see what changes in the brains of mice.

Venema:

That’s the main change we see in mice is we see increased folding. We get more packed into a fixed skull space.

Hoogerwerf:

If you’re wondering if more folds in the brain actually lead to the kind of changes in intelligence that we’re talking about, well, the mice did show some evidence of that and so I ask the natural question, “Are we creating a race of super genius mega mice?”

Venema:

Well, in one of these studies, when you put that particular gene into mice and they run them through some learning tests later on it, they do show some improvement, so yeah. Which isn’t too surprising because they’ve got more neuronal capability, they’ve got more neurons in there. I don’t think they’re about to take over the world though.

Stump:

But what we do learn from this is that the genetic change might possibly have led to creating a race of very special primates that did take over the world.

Hoogerwerf:

The kind who can figure out how to make vibrating coils of wires, send symbolic language across the globe into the small handheld boxes we keep in our pockets.

Stump:

How did we do?

Hoogerwerf:

Well, I can speak for myself and say that this is more interesting to me than when I first read the abstract you sent over, and it definitely helps to have dug in a bit to some of the basic science of genes and brains.

Stump:

Well, let’s hear your summary then.

Hoogerwerf:

Is this a quiz or something?

Stump:

Let’s call it a comprehension assessment tool.

Hoogerwerf:

Well, sounds like a quiz. That’s fine, I studied for this one. Scientists have found a way that parts of our DNA that weren’t coding for anything can start coding for something, something that wasn’t a gene becomes a gene, and the way that happens is some bits of RNA that are copied are stuck inside the nucleus. Lots of these are always stuck inside the nucleus, but some of them get some new luggage tags so that they can get outside the nucleus where they meet up with a ribosome and tell the ribosome how to assemble an amino acid that turns into a protein. One of these new genes that arose this way appears to build proteins in a way that makes our brains more heavily folded, making us smarter.

Stump:

I think that’s right. At least that’s what I learned from us too.

Hoogerwerf:

And from Dennis.

Stump:

Yes, especially from Dennis.

Hoogerwerf:

I might need some more folds in our brain before I can really understand this. Do you have any philosophical or theological reaction to this?

Stump:

Oh, now you’re speaking my language. No, not really. I guess it continues to show that scientists keep figuring out things about the mechanisms of evolution and that’s really cool. But I don’t really see this as the kind of scientific discovery that’s going to prompt me to rethink some core doctrine in theology or philosophy. It definitely, I guess, fits into the awe and wonder category we talk about sometimes.

Hoogerwerf:

I think it’s also helpful to put this into perspective of how revolutionary it all is.

Stump:

Yeah, this isn’t like we figured out nuclear fission overnight or something.

Hoogerwerf:

It’s not the kind of discovery that means a bunch of stuff we used to think is now wrong or upsets our previous understanding of evolution or something.

Stump:

Yeah, no, that kind of discovery is pretty rare. More often, science is figuring out what’s happening in the margins, and that doesn’t mean it’s not exciting.

Hoogerwerf:

Right. Science isn’t about making huge world shaking discoveries every day. More often it’s adding little bits of knowledge, building up our understanding of the world one piece at a time.

Stump:

But these pieces matter. They’re the foundation upon which we build the big ideas, the grand theories, and every now and then, one of these little bits turns out to be a key piece of a much larger puzzle.

Hoogerwerf:

This discovery is a good example of that. It’s not a game changer in the sense that it overturns our understanding of evolution or the human brain, but it does provide a fascinating glimpse into the process that helps make us who we are.

Stump:

All right. There you have it.

Hoogerwerf:

Thanks to Dennis Venema for helping us to understand what this is all about and why this is an exciting new discovery.

Stump:

If there are other scientific studies that you think need some unpacking or maybe just to be looked at through a philosophical or theological lens, send them our way. Or you can always send us feedback, questions, or comments at podcast@biologos.org. Thanks as always for listening.

Hoogerwerf:

Language of God is produced by BioLogos. It has been funded in part by the Fetzer Institute, the John Templeton Foundation, and by individual donors and listeners who contribute to BioLogos. Language of God is produced and mixed by Colin Hoogerwerf, that’s me. Our theme song is by Breakmaster Cylinder. BioLogos offices are located in Grand Rapids, Michigan in the Grand River Watershed. If you have questions or want to join in a conversation about this episode, find a link in the show notes for the BioLogos forum, or visit our website, biologos.org, where you will find articles, videos, and other resources on faith and science. Thanks for listening.