The Genes Who Came in for the Cold

Groups of people living in cold parts of the world have had thousands of years to adapt to the climate. And adapt seems to be what they’ve done! Among other genes, there’s one that seems to particularly make a difference . It’s called TRPM8, it’s part of controlling how you feel the cold, and research from UCL’s Aida Andrés seems to show that it’s helped us evolve to live in northern latitudes. Aida spoke to Phil Sansom... 

Aida - We studied a gene that encodes for a cold receptor. And what we found is that this gene has helped humans adapt to living in parts of the world where it's cold.

Phil - So this is a receptor for the cold that's in our skin?

Aida - Yeah. So it's in the nerves and it will tell your brain that it's cold.

Phil - What's the gene called?

Aida - TRPM8.

Phil - TRPM8...

Aida - Yes. So what we see in this gene is that there's a genetic variant that shows really large frequency differences between people that live in different places in the world. And this is something that is really unusual.

Phil - So if I live in, for example, Finland, I have a much higher chance of having one version of the gene; and if I live in Saudi Arabia, I guess I have a much higher chance of the other version?

Aida - Yeah, that's exactly right.

Phil - Aida, this sounds like a big pattern! Why did no one notice this before?

Aida - I think one of the reasons is that: the really striking thing about this particular gene is that you have correlations with latitude, and you really have to go after this pattern in order to see it. And when we looked at the frequencies in a map - that is when we saw the correlation with latitude. Plus, there's something else that is very interesting about this gene, and it's that this variant is not in the gene itself. It's in the regulatory part of the gene - it changes how the gene is expressed.

Phil - So if you look specifically at the TRPM8 bit, you're going to miss this change, because it's actually slightly further up the genome in the bit that's controlling which genes get actually turned into real, useful stuff?

Aida - That is correct. So the protein itself shows no differences between people in different populations. And what you have is this bit that is right before the gene, and that affects how it is expressed.

Phil - Okay, if I live somewhere northern, does my version of how this gene works - does it make me more sensitive to the cold, or less? Because I would think less, right?

Aida - So if your ancestors are from very high latitudes, you have most likely higher sensitivity to cold, actually.

Phil - I sense the cold more!

Aida - You do.

Phil - Why?

Aida - I know! I have to say, this is not very, very strong evidence, so the studies are small. But if the current studies are confirmed, I think that what tells you is that if you live in Finland... well, maybe it matters really very much if it's starting to get cold, that you notice that that's the case, and then your body can adapt, and maybe your behaviour even can adapt.

Phil - You're saying it's possible that because it's so important that we sense the cold - I mean, we don't want to die of cold - that if your ancestors came from your wintry place, then they need to be able to sense the cold really well so that they can go inside and put a fur on or something?

Aida - That's exactly right. I think that it's possible what they are telling us is that something that was not a very strong, selective pressure in some parts of the world, became a very strong, selective pressure. You really need to be able to feel the cold coming, and then you adapt to that.

Phil - Does that fit with our kind of colloquial myths of someone from a hot country coming to, I don't know, to Scotland and going, "oh my God, it's so cold here. How do you stand it?"

Aida - I think that what is happening here is that we're talking specifically only about genetic changes, right? Then on top of that, you have all of the physiological adaptations to cold temperature that people have through their lifetime. That's why we can move from one place to another and adapt also - because we're all so flexible.

Scientists have just broken the record for oldest DNA ever sequenced - using some mammoth teeth that are over a million years old. That’s so long, in fact, that the DNA inside has mostly broken down into tiny scraps, many of which are indistinguishable now as being from a mammoth. But thanks to some amazing techniques, Love Dalénand his colleagues have not only pieced the scraps together, but also uncovered part of the mammoth family tree, as well as some hints about when they got their woolly fur. Love told Phil Sansom the story...

Love - We managed to recover DNA from three mammoth specimens that are more than 1 million years old. And this is the oldest DNA ever recovered.

Phil - That isn't just the oldest DNA, right? That's by far the oldest DNA!

Love - This is by far the oldest DNA recovered to date. The previous record, if you wish, was approximately 650,000 years old. So we are nearly doubling that record with these mammoths.

Phil - What were the samples in this case?

Love - The samples were teeth - molar teeth - from three different mammoths from three different localities in Siberia. These specimens were actually found in the 1970s by a Russian palaeontologist named Andrei Sher. It actually took until 2017 until we felt that we had the technology and the know-how to do this. We had to use very new methods to identify which of all these billions of short DNA sequences we generated actually came from mammoth.

Phil - And what did you find inside? Because you said that the DNA... you had it in very short pieces?

Love - What we see in the data, once we get it, is the DNA is degraded into extremely small fragments. Normally a chromosome is well above 100 million base pairs or letters long, but in this case, our DNA sequences are on average between 40 and 50 base pairs long. So basically the genome is broken down into many, many millions of small pieces. And we also see that the vast, vast majority of DNA in these samples are not from mammoth; they are instead from bacteria; there is also DNA from plants in the sediments; and there's DNA from humans. Imagine that you have a puzzle with millions or even billions of small pieces that you have to piece together, and all we have to go by is the cover of the box. And in our case, that is the African elephant reference genome. But the problem here is that we don't only have one puzzle; instead, we actually have maybe 10 different puzzles, where the pieces have been mixed together. And the challenge here is to find the pieces that only belong to one of those puzzles, and then put them together in the right order.

Phil - Did you manage it though? Did you get the full jigsaw puzzle made for each of these three teeth?

Love - Yes and no. We managed to put together the puzzles as well as could possibly be done, but only for one of these mammoths do we have all the pieces in the puzzle. For the other two, we have partial genomes, but from a sort of population genomic perspective, that doesn't really matter; what matters is that we have enough data from each individual so that we can say something about their population history and relationship to other mammoths.

Phil - Right, so were they all very different kinds of mammoths?

Love - Well, one of them to our surprise came from a previously unknown type of mammoth that we didn't know existed. We refer to it as the Krestovka lineage.

Phil - Krestovka?

Love - Yes. The second specimen was actually what we expected to find; our expectation was that this one would be the ancestor of all wooly mammoths, and indeed that's what we find. And the third specimen is also interesting because it's a bit younger, it's about 700,000 years old, and this is actually one of the first known woolly mammoths.

Phil - Do you have any idea what this lost group of mammoths would've looked like?

Love - No, we didn't get enough genomic data to actually say anything about the sort of physical appearance about the Krestovka mammoth. We did get enough data from the other million year old mammoth, that was the ancestor of the woolly mammoth. This one is likely what we refer to as the steppe mammoth. Before this study it has been a bit unknown what they look like, because what we have are bones and teeth and so on from them, and tusks. So we knew they were big - they were much bigger than wooly mammoths - but what we now can see is that they actually appear to have had nearly all of these cold adaptations that we also see in woolly mammoths. They had woolly fur, adaptations for thermoregulation, and they probably also had this gene variant that made them slightly less sensitive to cold temperatures, which we also see in woolly mammoth.

Phil - I keep going back to the 1 million years old figure. Are we going to keep seeing these dates go further and further back? Or is that it, call it a day, 1 million - we're done!

Love - I don't think we're done at all. I mean, we can see in the data that the specimens are close to the limit, but they are not at the limit. So we know based on this data that we can go further back in time. The question is how far. These theoretical models basically say that there is no DNA at all left, the limit there is something like 7 million years. But at that limit the DNA is going to be broken down into very small fragments, like a few base pairs, and we can't work with that, because you can't prove that it comes from the animal in question. So the real question is: how far back in time can we go, and still be able to identify these fragments as being from mammoth or whatever animal we analyse? I think we can go beyond 2 million.