黑料吃瓜资源

Transcript

AA: Hello again, everyone! I鈥檓 Andrea Alfano, and I鈥檓 of course joined again by my co-host, Brian Stallard.

BS: Hi, everybody! If you listened to our first two episodes, you know that on Base Pairs we like to look at the ways in which harnessing the power of genetic information has already shaped our world, and how genetic information is becoming an even more powerful tool today, as technology advances.

AA: So far, our stories have been set either in the past or the present. But today, we鈥檙e really going to straddle both鈥攂ecause we鈥檙e going to be talking about using DNA evidence to piece together the past.

BS: You鈥檙e talking about how we can trace DNA samples, CSI-style?

AA: That鈥檚 part of it, yeah. Except I鈥檓 not just talking about matching the DNA to a criminal, like you might have seen on Law & Order. I鈥檓 talking about forensic investigations that reach deep into humankind鈥檚 past, matching bits of DNA across thousands of years. But, our story does start out with a murder.

NOVA: 鈥淗e was found in a glacier, frozen in time for 5,000 years. An ancient murder mystery. You can鈥檛 help but ask, what is his story? Secrets hidden in his genetic code. We鈥檙e rewriting the history of humankind.鈥�

BS: Whoa鈥� who turned on the drama? What did I just listen to?

AA: Ha! I did warn you that we鈥檙e starting with a murder. What you just heard is from the trailer for a recent TV special called 鈥淚ceman Reborn鈥� from PBS鈥檚 NOVA series. And that mystery man goes by the name of 脰tzi these days. He was named after the place where he was found鈥攈igh up in the 脰tzal Alps, on the border between Italy and Austria. Some tourists found him sticking out of a glacier as they were hiking up a mountain back in 1991.

BS: I remember. 脰tzi was reportedly discovered by a pair of adventurers hiking those frozen peaks.

AA: You can just imagine how bewildered they must have been. One moment you鈥檙e admiring the beauty of a snowy mountain range, the next, you鈥檙e standing over a frozen corpse.

BS: An accident of global warming, perhaps? He was so well-preserved that they at first thought 脰tzi had died recently. But it turns out they鈥檇 stumbled upon the oldest intact mummy that anyone鈥檚 ever found.

LB: He鈥檚 got all of his parts, minus a few fingernails, but he鈥檚 got all of his internal organs.

AA: That鈥檚 Lindsay Barone. She鈥檚 an anthropologist who works over at the Cold Spring Harbor Lab鈥檚 DNA Learning Center.

LB: But, more interestingly, it appears that he was murdered. And so, trying to figure out what happened, he clearly didn鈥檛 die of natural causes, so what drove that? Why was he moving around the Alps with all of his belongings? He had an axe, he had clothing, he had a first aid kit鈥攈e had all of this stuff with him. So trying to reconstruct those movements and figure out what鈥檚 going on.

AA: Lindsay knows so much about 脰tzi because apart from the South Tyrol Museum in Italy鈥�(BS: which is near where 脰tzi was found)鈥攖he DNA Learning Center is the only place in the world where you can find an official 脰tzi replica.

BS: 鈥淩eplica鈥� really doesn鈥檛 do it justice. It was created by using an enormous 3D printer to make a mold, which was then filled with resin and painstakingly hand-painted. The artist even got to touch the real 脰tzi to make sure he got certain textures right.

KID: I saw the process on the television up there and it looked like it took a lot of work and effort. But I think it paid off because it looks really realistic.

AA: This class is one of many that has travelled to the DNA Learning Center to learn about 脰tzi.

KID: Science today is so advanced that it can just get DNA out of pretty much anything.

BS: Scientists have indeed sequenced 脰tzi鈥檚 DNA, and have been able to learn quite a bit about him from it.

KID: Also they can figure out everything like his eye color and his blood type, since obviously they didn鈥檛 find much blood. They could even find if he had heart disease or if he was lactose intolerant or not.

AA: But what鈥檚 really cool is that high school students also get to learn about 脰tzi themselves. For one activity, they get to sequence some of their DNA鈥�(BS: that sequence is made up of the chemical base pairs in DNA, known by their initials, A, T, C, and G)鈥攁nd compare their sequences to those of their classmates, other people from around the world, and ancient humans including Neanderthals and 脰tzi.

LB: So what they鈥檙e looking for is whether or not they have the same base pairs or whether those base pairs differ. And the more base pairs the students have in common with the sequence they鈥檙e comparing to, the more similar genetically they are.

BS: It makes sense. Over time, the genome accumulates a bunch of random mutations. So if you鈥檙e only very distantly related to another person or another organism, you鈥檒l have more differences in your sequences even if you鈥檙e looking at a gene that you share.

LB: So 脰tzi is very, very similar to the modern European reference sequences. A lot of students tend to be very similar to Otzi as well.

AA: When the student compare their sequences to those of Neanderthals, though, they start to see more differences. Neanderthals and humans went their separate evolutionary ways around half a million years ago, and are considered a different species than the humans that are around today.

KID: List the differences between the Neanderthal and human skulls. I feel like their skull was bigger than the human鈥攜eah, bigger skull. And their ribcage was a little bit bigger. But they鈥檙e actually pretty similar.

BS: At the DNA Learning Center, models of human and Neanderthal skeletons stand side by side so that you can compare their physical features. And even after a half million years apart, the similarities are striking.

KID: It may seem old to us but for the history of like humans, it鈥檚 really not that old.

AA: He鈥檚 right. Half a million years isn鈥檛 all that long in evolutionary time. In fact, humans and Neanderthals weren鈥檛 even truly apart for that entire time鈥攕ince they were so similar, they could and sometimes did mate with one another. Most of us even have traces of these encounters in our DNA.

LB: Modern humans that are not of recent African origin tend to have between one and four percent of their DNA from Neanderthals. Depending on the ancestry of the student or the ancestry of the individual that is being compared to the Neanderthal, there might be a few more differences or not quite as many.

BS: Our textbooks tells us that modern humans鈥擧omo sapiens鈥攁nd Neanderthals are different species, but they鈥檙e still close enough to have offspring together. Then what makes them different species?

AA: That is a very good question.

AS: So this gets at a kind of a skeleton in the closet in evolutionary thinking.

AA: That鈥檚 Adam Siepel鈥�(AS: professor at 黑料吃瓜资源 and Chair of the Simons Center for Quantitative Biology)鈥攁nd I asked him that question about modern humans and Neanderthals.

AS: We don鈥檛 really know what a species is. We could argue about whether they really could be called separate species and some people indeed argue that they should all be considered members of the same species.

BS: Wow, even people who study this stuff for a living are confused about this.

AA: It can be confusing. But, all of that seemingly chaotic gene swapping鈥�(BS: you mean mating)鈥攜eah, all of this mating of modern humans and Neanderthals actually helped Adam and his team discover surprising new parts of the history of humankind.

AS: We found evidence of an earlier migration out of Africa, resulting in gene flow鈥� interbreeding鈥攂etween modern humans and Neanderthals some 50,000 years before people generally think of modern humans having emigrated out of Africa at all.

BS: So modern humans started out in Africa, and eventually migrated out and explored other parts of the world鈥攖hat鈥檚 the famous 鈥渙ut of Africa鈥� migration. And now Adam is saying that wasn鈥檛 the first time modern humans left Africa?

AA: Yep. The famous 鈥渙ut of Africa鈥� migration was about 50,000 years ago, but Adam and his team found evidence that some adventurous modern humans left way earlier than that鈥攁bout 100,000 years ago. And they were able to figure it out because early modern humans and a group of Siberian Neanderthals had children together around that time

BS: What kind of evidence? Ancient bones?

AA: Yes鈥攚ell, Adam鈥檚 team didn鈥檛 discover the ancient bones. They just work with genomes, and they were able to get the genome of a Siberian Neanderthal from another group of scientists. Adam鈥檚 鈥渓aboratory鈥� is essentially a collection of desktop computers in an office, connected to some very powerful supercomputers. He does experiments by gathering genome sequences and crunching numbers to compare them and learn about them.

AS: I鈥檓 also fascinated by the idea of using powerful statistical and mathematical and computational tools to sort of decode this hidden level of meaning in genome sequences to be able to get at these secret stories by being clever enough in the way we decode them.

BS: It鈥檚 kind of like that activity the kids were doing before at the DNALC, where they compared their sequences to those of 脰tzi and Neanderthals to see where the base pairs differ. Adam鈥檚 work seems like that, but all grown up.

AA: Right, it鈥檚 a lot like that. So Adam and his team were working with this Siberian Neanderthal genome, and three other ancient genomes鈥攖wo are from Neanderthals who lived in Europe, and one from another species of ancient human that was also living in Siberia. And they compared these ancient genomes with sequences gathered from modern humans with different ancestries.

AS: What we do is we build what we call genealogies鈥攖hey鈥檙e sort of like family trees that are describing the relationships among these individuals across the genome.

BS: So Adam is building a family tree that goes back tens of thousands of years, but he鈥檚 only got a few family members within a giant family to work with. That sounds kind of impossible.

AA: It is pretty amazing. It鈥檚 important to keep in mind, though, that these family trees don鈥檛 show direct relationships between individuals, all of the mothers and fathers and children along the way. The individuals whose genomes Adam analyzed sort of served as representatives for large populations of humans.

BS: So it鈥檚 a tree that shows when different populations of humans separated from one another.

AA: Right. And they can tell how much time passed between these separation events by looking at the sizes of chunks of the genome that are similar between these individuals.

AS: We can use that as a clock when we try to date these ancient events. So, for example, your parents have fairly large chunks of DNA from your grandparents, right, but smaller chunks of DNA from your great grandparents and even smaller chunks of DNA from your great-great grandparents, and as you go back many, many generations, those chunks get smaller and smaller.

AA: When they compared the Siberian Neanderthal鈥檚 genome with those of modern humans from today, they saw something that really surprised them.

AS: We saw this strange pattern that we couldn鈥檛 explain, and that, to our knowledge, hadn鈥檛 been reported previously, indicating gene flow from modern humans into Neanderthals鈥�(AA: meaning chunks of modern human DNA in the Neanderthal鈥檚 genome)鈥攁nd affecting only this one Neanderthal sample, the one that was found in the Altai Mountains in Siberia

AA: And, the chunks of Neanderthal DNA that we see in the genomes of many modern humans today鈥�

BS: Like what Lindsay was talking about earlier, how students with certain ancestry had more similarities to Neanderthals.

AA: Right, those are a lot bigger, on average, than the chunks of modern human DNA that Adam and his team found in this Siberian Neanderthal鈥檚 genome.

BS: Ohhhh, so that means that the encounter that left modern human DNA in the Neanderthal genome happened a lot earlier than the encounter we already knew about鈥攖he one that left little bits of Neanderthal DNA in our own genomes today.

AA: Yep. Since this unexpected genetic trace of modern humans showed up only in these Neanderthals who lived in Siberia, Adam and his team proposed that a group of early modern humans, who are now otherwise lost to history, left Africa a lot earlier than the previously know 鈥渙ut of Africa鈥� migration 50,000 years ago. And that conclusion held up when Adam鈥檚 team put it to the mathematical test.

AS: These methods are quite intensive鈥攕ome of our programs will run for two weeks or more on a computer cluster involving hundreds of compute nodes.

BS: But if we know that humans and Neanderthals had children together at least a couple of times, does that mean it happened many more times that we don鈥檛 know about?

AA: That we can鈥檛 say for sure. But we do know that those human-Neanderthal hybrid children went on to live among humans and Neanderthals and seemed to be accepted just fine in both communities.

AS: What I think is really interesting about our finding is that it suggests both of these events occurred. Human-Neanderthal hybrids were absorbed both by modern human and by Neanderthal populations. I think it鈥檚 very interesting, and in some ways it鈥檚 sort of encouraging about us all being one big happy family, maybe more so than people have recognized.

BS: A big, happy, human family. That is pretty encouraging.

AA: Right? I think so. The students at the DNALC pick up on this, too, when they realize how genetically related we all are.

LB: It鈥檚 one of those things that I think really helps clarify their position with respect to all of these people that came before them, with respect to other people that are living now, with respect to the Neanderthals and other species鈥攜ou know, they get really excited about being able to make those connections for themselves.