The tale of how humans lost their tails

A tail as old as time...
01 March 2024

Interview with 

Itai Yanai, NYU Grossman School of Medicine

APE

An ape

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Humans, chimpanzees, gorillas and orangutans do not have tails. It sets us apart from other primates, but suggests that our shared evolutionary ancestors had them. So why did we lose them, and how? Itai Yanai is a geneticist and systems biologist at NYU Grossman School of Medicine, and the way this study began was literally as a pain in the arse for one of his colleagues…

Itai - The story starts with a student in my lab, his name is Bo Xia. Bo got injured while sitting in a car. So he moved over and he sat unfortunately on a belt buckle and he injured his tailbone. It all sort of culminated in a very simple question, how did we lose our tail? The chimpanzee, they don't have a tail, the gorilla doesn't have a tail. But if you go to something more distantly related like the macaque monkey, the macaque monkey of course still has a tail.

Chris - Is one way to try and find out why we even had a tail historically and how these other animals have a tail. Is it, you go and look at them and ask, well, what genes have they got that might make them have a tail? Because then you can, you can ask, well, are they different in us?

Itai - Right. So what Bo did is he studied the genome using a genome browser that allows him to see very conveniently, what does our genome look like? And particularly what does it look like when you compare it to the genomes of other animals like the macaque, like the gorilla and the chimpanzee. And what he saw is that there is a particular element that's in a region that doesn't look like it would be important. It doesn't look like it would be very disruptive. However, it had three interesting things about it. One, it was in this gene that was known for a very long time that it's responsible for the tail. Two, it's an element that we could see at the right time. Why is it at the right time? Because all the animals that have this change don't have a tail. And all the animals that do still have a tail lack this element. So it was the right pattern. And three, knowing molecular biology, Bo could see that that actually would be highly disruptive. So now Bo had a hypothesis, this change is how we lost our tail.

Chris - So in summary then you home in on this region of the DNA, which we know is linked to animals having tails or tail function. And that in animals that appear not to have a tail, there is a region of that gene which has a change in it, and it's in all the animals that don't have a tail. And it appears in such a way that it would disrupt or affect how that gene would work, which does look like a smoking gun genetically then.

Itai - Exactly. So now the question is what do you do with this? Bo and I sat down together and we designed this experiment where we would generate mice that have exactly the same kind of mutation that we saw that we have. And the prediction would be that if you make mice like that, they would also lose their own tails.

Chris - And do they? If you introduce this same change into a mouse, do you end up with mice with truncated or absent tails?

Itai - You know, they do and I still get goosebumps every time I think about it. They do. They're born without a tail. And although it took years of work, four years of generating mice and studying them, what we saw was that there's a correspondence between how much disruption we put in and the length of the tail.

Chris - Now most things that get fixed in evolution confer some kind of advantage. So on the one hand we lose a tail and gain 'taillessness'. So what would've been the advantage that would've meant this was so strongly selected for in the group of animals that were our ancestors back in history?

Itai - It was 25 million years ago, so we'll never know for sure. The way we speculated is that actually it could very well be that this mutation was the fundamental mutation that led to us sitting down here and talking on The Naked Scientists podcast that facilitated us to come down from the trees and have a life on the ground where we now stand on our two feet.

Chris - One issue though is that that part of the body, how we form the backbone and the spinal cord that overlays it, there is a small group of unfortunate people in the population who suffer neural tube defects. The condition spina bifida where the tube that forms the spinal column doesn't close up properly at one end, the tail end. Now does this link up with, or is that associated with, this particular gene and is there therefore a risk if you disrupt it that you're going to get more of that happening?

Itai - Yeah, you know, this was a completely unexpected aspect of this project that when we made the mice with those mutations, some of them were born with a condition that looked remarkably similar to the human condition that you mentioned with neural tube defects. And I think now it could lead to a series of new studies that promise to make some kind of advancements on how we treat this disease. And yet that's the magic of science, that if you let people follow their curiosity, it will lead to interesting places that are just unpredictable.

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