by Pbo, Svante
Chapter 22
A Very Unusual Finger
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On December 3, 2009, I was attending a meeting on the rat genome at the Cold Spring Harbor Laboratory. I was there to describe a project on artificial domestication in rats that my group had been working on for the last few years. As I walked from the dining hall to the lecture hall after breakfast, my cell phone rang. It was Johannes Krause calling from Leipzig and he sounded strangely excited. I asked him what the matter was. He asked me if I was sitting down. When I said no, he said I’d better sit down before hearing what he had to tell me. Starting to worry that something terrible had happened, I sat down.
He asked me if I remembered a small bone that we had gotten from Anatoly Derevianko in Russia (see Figure 22.1). Anatoly is the president of the Siberian branch of the Russian Academy of Sciences and one of Russia’s foremost archaeologists. He had started his career back in the 1960s and was not only very influential in the Russian academic world but also politically well-connected. Over the past several years that we had worked with him I had come to appreciate him more and more, also as a friend. Anatoly has a very warm smile and I have found him always polite and open to collaboration. He is also a very experienced field archaeologist and physically active. In the large lake close to his institute in Novosibirsk he was known to go for kilometer-long swims. Although very different in appearance from my professor of Egyptology, Rostislav Holthoer, who was of Russian descent, Anatoly shares with him the great capacity for friendship and loyalty I find typical of Russians. I count myself very fortunate to collaborate with him.
Some years previously, Anatoly had visited our laboratory and given us a few small bones in plastic bags. They had been excavated in a spot called Okladnikov Cave in the Altai Mountains in southern Siberia, where Russia, Kazakhstan, Mongolia, and China meet. These bones from Okladnikov Cave were too fragmentary to tell what type of human they had come from, but we extracted DNA from them and showed that they contained Neanderthal mtDNA. Together with Anatoly, we then published a paper in Nature in 2007 that extended the range where Neanderthals had lived by at least 2,000 kilometers further east of what had been commonly believed.{62} Prior to our paper, no Neanderthal had been confirmed east of Uzbekistan.
In the spring of 2009 we received another bone fragment from Anatoly. His team had discovered that fragment during the previous year in Denisova Cave, another cave in the Altai region located in a valley that connects the Siberian steppes in the north to China and Mongolia in the south. The bone was minuscule, and I hadn’t attached very much importance to it, thinking only that we would see whether it contained any DNA at some point in the future when there was time. Perhaps it would prove to be Neanderthal, which would enable us to gauge the extent of mtDNA variation among the easternmost Neanderthals.
Figure 22.1. Anatoly Derevianko with colleagues. Photo: Bence Viola, MPI-EVA.
Johannes had now found the time to extract DNA from the bone; and Qiaomei Fu, a talented young graduate student from China, had made a library and used a method that Adrian Briggs, the British graduate student in our lab, had developed to fish out mtDNA fragments from the library. They found a very large amount of mtDNA—in total, 30,443 fragments, which enabled them to assemble the complete mitochondrial genome with a very high degree of accuracy. In fact, each position in the mtDNA was seen an average of 156 times, unusually high for an old bone. That was good news, but it wasn’t why Johannes asked me to sit down. He had compared the mtDNA sequence of the Denisova bone to the six complete Neanderthal mtDNA sequences that we had previously determined as well as to mtDNA sequences from present-day humans from around the world. Whereas the Neanderthals differed from modern humans at an average of 202 nucleotide positions, the Denisova individual differed at an average of 385 positions—almost twice as much! In a tree analysis, the Denisova mtDNA lineage branched off well before the modern human and Neanderthal lineages shared a common ancestor. When Johannes calibrated the rate of substitutions by assuming that humans and chimpanzees split 6 million years ago, then the Neanderthal mtDNA split from the human lineage about half a million years ago—just as we had previously shown—and the mtDNA of the Denisova bone branched off approximately 1 million years ago! I could hardly believe what Johannes was telling me. This was neither a modern human nor a Neanderthal! It was something else, entirely.
My head was spinning. What extinct human group could have split off from the human lineage a million years ago? Homo erectus? But the oldest H. erectus fossils outside Africa were found in Georgia and were about 1.9 million years old. So H. erectus were supposed to have left Africa and thus to have split from the lineage leading to present-day humans almost 2 million years ago. Homo heidelbergensis? But they were thought to be the direct ancestors of Neanderthals and would then presumably have diverged from the modern human lineage at the same time as Neanderthals. Was this bone from something totally unknown? A new form of extinct human? I asked Johannes to tell me everything about this bone.
The bone was indeed tiny, the size of two grains of rice put together. It came from the last phalanx of the little finger (see Figure 22.2), the outermost part of a pinky, from what was probably a young individual. Johannes had used a dentistry drill to remove thirty milligrams of material from the bone, and from this tiny amount of bone powder he had extracted the DNA that Qiaomei had used to make the library. Given how much mtDNA she and Johannes found, the DNA preservation in the bone must be exceptionally good. I would be back in Leipzig in three days and I told him that we would meet then and decide what to do.
After I hung up, I couldn’t bring myself to listen to presentations about how the genomes of different rat strains differed from each other. It was a sunny and snowless winter day in the New York area. I spent the morning walking along the windy beach below Cold Spring Harbor and thought about the young person who had died far away in a Siberian cave many thousands of years ago. All that remained of that life was a tiny speck of bone, but it was enough to tell us that she represented something unknown to us, a group of humans who had left Africa before the ancestors of the Neanderthals but after Homo erectus. Could we find out what this group was?
When I got back to Leipzig I sat down with Johannes and the others to discuss our next steps. The analyses of the Neanderthal genome were drawing to a close, so people had time on their hands to think about these startling findings. The first thought was whether there could be something wrong with the DNA sequence Johannes had reconstructed. Qiaomei and Johannes had retrieved thousands of mtDNA fragments and much less than 1 percent of them carried substitutions that were suggestive of contamination. Since the mtDNA looked quite different from present-day human mtDNA, it couldn’t be contamination from anyone today. Earlier in my career I had often worried about fragments of mtDNA that thousands or millions of years in the past had become integrated on a cell’s nuclear chromosomes. Such mtDNA fossils could sometimes be mistaken for an actual mtDNA sequence. Fortunately, the circular shape of the mtDNA enables us to separate nuclear mtDNA fossils from real ones. The DNA sequence Johannes had reconstructed from overlapping fragments must have derived from a circular molecule. I didn’t see how our findings could be wrong. Nevertheless, Johannes and Qiaomei would do a separate, independent DNA extraction from some powder that was left of the bone sample and repeat what they had done. But this was more of a formality. I was certain he would get the same results.
Figure 22.2. The small finger bone discovered in 2008 by Anatoly Derevianko and Michael Shunkov in Denisova Cave. Photo: MPI-EVA.
I turned to the question of what this unusual person could have been. If there were more bones in the cave, that could help us figure this out. I was told that Anatoly Derevianko had given us only a portion of the bone so there must be a bigger piece still in Novosibirsk. Perhaps there were also other bones that would give us a hint of what this person could have looked like or that we could use to extract more DNA. We clearly needed to visit No
vosibirsk.
I immediately e-mailed Anatoly and said that we had some very unexpected and exciting results and that I wanted to present these to him in person as soon as possible. I said that we would also be very interested in further analyzing the other part of the bone, and perhaps to date it. Anatoly answered the next day and asked for more details about the results. I summarized them for him and we arranged for me to visit Novosibirsk, along with Johannes as well as Bence Viola, a jovial archaeologist of Hungarian descent, in mid-January 2010. Bence specializes in Central Asian and Siberian paleontology, and we had often worked with him in the past. I had just succeeded in convincing him to come to Leipzig from Vienna to work with us and the paleontologists at our institute. A fourth person who would join us was Victor Wiebe. He had done his PhD in Novosibirsk in the ’70s and knew Anatoly and several other people there from that time, and he had been working with me for twelve years. On this trip he would serve as a much-needed interpreter. I had studied Russian thirty-five years earlier, during my military service in Sweden, but by that point I remembered only crude questions one would pose to prisoners of war. They were not suited for scientific discussions.
After a stopover in Moscow and a long overnight flight on to Novosibirsk, we landed in the early morning of January 17. A digital display at the airport terminal showed the time as 6:35 a.m. Then it switched to the temperature: −41°C. When our luggage arrived I opened my bag and put on all the clothes I had. The air outside the terminal was very dry and the snow was like powder swirling around our feet as we quickly made our way to the car. When I breathed in, the sides of my nose tended to freeze to the septum.
The drive to Akademgorodok took an hour. As the name suggests, Akademgorodok is a city that was built solely for scientific pursuits in the 1950s by the Soviet Academy of Sciences. At its heyday, it housed more than 65,000 scientists and their families. After the collapse of the Soviet Union, many scientists left Akademgorodok and most institutes there had declined. But by 2010, the Russian governments and several large companies had been investing money in the city for almost ten years, and there was a sense of tentative and cautious optimism around the city.
We were housed at the Golden Valley Hotel, which had been converted from a typical Soviet nine-story apartment building. I had visited the hotel once before; one of my most vivid memories from that visit was the lack of hot water, which drove me every morning to walk a good half-hour through the birch forests to swim in a nearby reservoir called the Ob Sea. That, however, was in summer, and I was more than a bit concerned about whether the heating system would work now. I needn’t have worried. When Johannes and I arrived at our room, we found not only was there hot water in the tap but the radiators were so hot that the temperature in the room was unbearably warm—about 40°C. There was no valve to turn the heating down, so we ended up opening the windows and letting in outside air that was almost 80° colder. We kept that window open for the duration of our stay.
We arrived on a Sunday, and our meeting with Anatoly wasn’t until the next day, so after a nap the four of us decided to take a walk. We were amazed to find a small ice cream vendor open for business. Feeling certain that this was the one and only time I would ever have an ice cream when it was −35°C out, I approached the shack. The woman who sold me the ice cream realized that I wasn’t local and urged me to eat the ice cream fast: once it reached ambient temperature, it would be rock-hard and impossible to eat. After quickly eating the ice cream we walked through the frosty forest to the beach where I had swum during warm summer mornings two years earlier. We were the only ones there. The sky was clear but the pale sun provided not even a trace of warmth. Fortunately there was no wind. Even the tiniest bit of air that made it into our clothing had a chilling effect. In fact, by this point my toes were numb and we quickly retreated to our overheated hotel rooms.
The next day we met with Anatoly in the spacious office he enjoyed as head of the Institute of Archaeology and Ethnography. Michael Shunkov, the archaeologist who led the excavations at Denisova Cave, was also present, as were some of their associates. Johannes presented his and Qiaomei’s findings, and everyone was taken aback. Was this a new form of extinct human, perhaps some form that was present only in Siberia or only in the Altai Mountains? There were in fact several plant and animal species endogenous to the Altai area, so the idea was certainly plausible. Over a lunch of delicious Russian cold cuts washed down with vodka, all served in Anatoly’s office, we excitedly discussed what we might have found. After some time, when the atmosphere was both animated and relaxed, I pointed out that the ultimate answer to our questions would be found in the nuclear genome. If we could sample the remaining, larger piece of the finger bone we would be able to sequence the nuclear genome and get a more complete picture of how this individual was related to people today and to the Neanderthals whose genomes we had just sequenced. At first I didn’t understand Anatoly’s answer to this request, which I blamed on my bad Russian and inebriated condition. But I was still puzzled after Victor’s translation. Anatoly was apparently explaining that he no longer had the other piece of the bone since he had given it to my “friend” about a year ago. Bewildered, I looked questioningly at Victor, Bence, and Johannes. What friend of mine? Did one of them already have it? But they looked as stunned as I was. Then Anatoly clarified. He had given it to “my friend Eddy, Eddy Rubin, at Berkeley.”
I have no idea how I looked or what I said after that. I knew that Eddy had been trying to get his hands on bones to sequence the Neanderthal genome ahead of us. But here we were learning that, for almost a year, he had had a much larger piece than we did of this particular bone that contained so much endogenous DNA that it would be possible to sequence the nuclear genome in a matter of a few weeks, without technical tricks or many hundreds of runs on sequencing machines. And we were still weeks from even submitting our Neanderthal paper to Science, let alone its publication. My recurring worst worry suddenly seemed about to come true: before we could publish there would be a paper from Berkeley presenting the genome of another extinct form of humans, sequenced to even higher coverage than the Neanderthal genome. Who would then care about our years spent painstakingly working on extraction techniques, on enriching for endogenous DNA, on teasing out the Neanderthal DNA from the vast excess of bacterial DNA? All these details would be important in the long run for use on the hundreds of bones that weren’t as miraculously well preserved as this one, but in terms of getting the genome of an extinct human relative, Eddy would have done it faster and better, simply because he got lucky.
I struggled to regain my composure and to say something that wouldn’t give my feelings away. But I managed only some mumblings about scientific collaboration. We soon left the meeting with a plan to meet our hosts for dinner later at the House of Scientists, the social center of Akademgorodok. Walking back to the hotel room, I didn’t feel the cold anymore. Johannes tried to console me. He tried to make me see that we should just continue doing the best work we could and forget about the competition. He was right, of course. But obviously we shouldn’t drag our feet. Now, more than ever, we had to be fast.
Dinner was an ebulliently friendly affair, as were all the dinners I have enjoyed with Anatoly. The food was excellent: salmon, herring, and caviar were followed by several delicious main courses. Toasts with good vodka were frequent throughout the evening and, as is customary in Russia, each dinner participant took his turn proposing a toast to some commonly appreciated theme, such as collaboration, peace, our teachers, our students, love, women, and so on. When I had first started traveling in the Soviet Union, I had loathed this custom, feeling immensely embarrassed when I had to mumble my way through a speech on a theme I didn’t enjoy talking about in front of a large dinner crowd. With time, though, I had gotten used to it and had even come to appreciate the fact that it allowed all participants at the dinner, even those whose social standing would not normally have allowed them to be heard, let alone dominate the conversation, to com
mand everyone’s undivided attention for a short time.
Undoubtedly I also had come to appreciate this custom thanks to the fact that, deep down, I’m a very sentimental person, a trait that alcohol often helps bring to the surface. And sentiments are what these toasts are about. I toasted, first, to our very fruitful collaboration and then to peace, pointing out how I had grown up in capitalist Sweden, and had been conditioned to regard a huge war in Europe as a likely scenario and Russia as our natural enemy. Since Sweden was officially neutral, the potential enemy I had been trained to face during my military service was officially and euphemistically named “the superpower,” but tellingly, the language spoken with prisoners during our war games was Russian. But the war everyone planned for never came. We never had to face each other as enemies. Instead we were sitting here as friends, working together and discovering amazing things together. Thanks to the alcohol, I was moved by my own words. As one of the youngest at the dinner, Johannes appropriately chose to toast his teachers. I realized how inebriated I was when he brought tears to my eyes by saying that he had two fathers in science: me, who had introduced him to molecular evolution and ancient DNA, and Anatoly Derevianko, who, during two field trips to the Altai and Uzbekistan, had introduced him to archaeology. In fact, I was so moved because these were truths that we wouldn’t normally share with each other.
We walked to our hotel after dinner along the main street of Akademgorodok. The night was very cold and dark, and the stars unbelievably bright due to the fact that the ice-cold air could hold hardly any humidity. But I didn’t notice. The tension from earlier in the day had caused me to down shots of vodka faster than I normally would have. In fact, I had the feeling that I hadn’t been so drunk since my teens. But as we unsteadily made our way down the snowy street, Bence told me something that instantly penetrated even my intoxicated mind. Earlier in the visit, Anatoly had given him a tooth that had been found nine years earlier in Denisova Cave. It was a molar (see Figure 22.3), probably from a juvenile, but it was huge. Bence said that he had never before seen a similar tooth, seeming unlike both Neanderthal and modern human teeth. In fact, he said, if he hadn’t known where it had been found, he would have thought that it had come from some much older human ancestor, maybe Homo erectus in Africa, or Homo habilis, or maybe even Australopithecus. It was the most amazing tooth he had ever seen. In our drunken state, we were sure that it must have come from the same person as the finger bone, and we felt certain this creature must really have been something we hadn’t seen before. In the Altai, there have long been rumors of mountain-dwelling snow men called Almas. As we made our way toward the hotel, we shouted that we had found an Alma! We joked that, if we could get a radiocarbon date from the tooth, we might find it to be just a few years old. This would explain why it contained so much DNA. Maybe these Yeti-like creatures were still living somewhere on the border between Russian and Mongolia. I don’t quite remember finding our hotel room and getting into bed that night.
