Time Travel with the Molecular Clock

CULTURE & SOCIETY_Personal Portrait

Migration isn’t a new phenomenon, but new insights suggest that modern-day Europeans actually have at least three ancestral populations. This finding was published by Johannes Krause and his colleagues in September and was prominently featured on the cover of Nature. As it happens, the paleogeneticist himself is currently thinking about migrating, and will henceforth travel through time as a Founding Director of the Max Planck Institute for the Science of Human History in Jena. For him, looking back millennia into the past seems to be no problem.

TEXT CATARINA PIETSCHMANN

he air is abuzz with chatter Almost two years have passed since Jo- from New Zealand who conducts, and clinking glasses. It’s a hannes Krause applied for a professor- among other things, linguistics research hot July afternoon in Tübing- ship in Kiel in connection with the MPI – would jointly set up the new institute. en and it seems like half the in Plön. “I wasn’t really suited for the It’s a future-oriented concept for town is out and about today position, to be honest.” And the twelve looking back into the past. It’s about –T in search of a table in the shade in Max Planck Directors who interviewed the history of mankind. About the evo- front of the historic, newly restored city him thought so, too. But then some of lution of language and of Homo sapiens, hall. Today, Johannes Krause decided to them asked him a question that took the anatomical modern human. They leave his institute, which is within walk- him by surprise: Since you’re already will apply their respective methods to ing distance, earlier than usual. If you here – could you see yourself setting up reconstruct – or disprove – the annals were to see him sitting here in the café a new institute for us? of human history. After all, linguistics – rebellious curls, gray T-shirt, boyish and genetics aren’t as different as they appearance, with a tangible enthusiasm A FUTURE-ORIENTED LOOK may seem at first glance. in his voice – you might easily mistake INTO THE PAST “Migration and merging are reflect- him for a college student in his senior ed not just in genetics, but also in lan- year, or at most a doctoral candidate. A What Krause didn’t know was that, at guage,” says Krause. “Russell Gray de- biologist, perhaps, or a philosopher. that time, the Max Planck Society was velops evolutionary trees of language The indolence of college life? That’s already planning to realign the MPI for families that show signs of merging as something the 34-year-old professor of Economics in Jena and was looking for well as splitting. This allowed him to archaeo- and paleogenetics at the Insti- a new Director. The members of the in- identify the time frame in which the In- tute for Archaeological Sciences doesn’t terview panel were aware of his excel- do-Germanic languages diversified.” have much time for. Especially now lent scientific career profile, which he While not a single word has been that he is about to leave for Jena to had built up under the guidance of his passed down to us from the prehistor- take on his position as one of the two mentor, Svante Pääbo, at the MPI for Evo- ic age, archaeologically proven migra- Founding Directors of the new Max lutionary Anthropology. And so it was tion patterns could serve as calibration Planck Institute for the Science of Hu- soon decided that he and Russell Gray – points. And since language (similar to man History. At the moment, Krause is a molecular biologist from Tübingen a genome) undergoes certain “muta- the youngest Max Planck Director – in- who focuses on the analysis of ancient tions” over time, models based on his-

credible! How is this possible? DNA, and an evolutionary biologist torical, archaeological and linguistic Photo: Sven Döring

70 MaxPlanckResearch 4 | 14 The spiral shape suits the expert on ancient DNA: Johannes Krause on the way to the top – inside the institute’s old building in Jena. Free-flowing dialog: Johannes Krause (left) and his Director colleague from New Zealand, Russell Gray, an evolutionary biologist with a passion for linguistics, have already set their sights on a number of joint projects. facts can help compute the time periods ple is the Austronesian expansion. Gray in Tübingen. He teaches classical ar- in which languages are likely to have studies (linguistically) the settlement of chaeologists the foundations of genet- split. “Over the course of the past 1,000 Polynesia via Southeast Asia that oc- ics. To him, it comes as no surprise that to 2,000 years, there are several exam- curred 3,000 to 4,000 years ago. “As a this approach would work out well; af- ples of populations that merged but result of the colonization that took ter all, he spent many years of his sci- adopted the language of the new loca- place over the past 500 years, many ge- entific career at the Leipzig-based Max tion. By contrast, the colonization of netic patterns have been overwritten. Planck Institute for Evolutionary An- America resulted in the language of the That’s why we’re currently trying to re- thropology, which follows a similar in- indigenous people becoming complete- construct the early settlement process terdisciplinary approach. ly displaced,” Krause explains. They using very old human DNA samples Paleogenetics is a young scientific have met only a few times so far, yet taken from that region,” Krause ex- field that didn’t came about until the the scientist from Tübingen is already plains, outlining their first plans. 1980s. Only a small number of labora- enthusiastically incorporating the re- He himself is particularly interested tories worldwide have the equipment search findings of his soon-to-be col- in how modern humans spread out and experience to analyze DNA sam- league from the other side of the globe across Europe. “Did they come in waves ples taken from mummies or ancient into joint project ideas for the new in- because of the recurring ice ages? We skeletons. Even the process of merely stitute. He and Gray plan to tackle don’t know.” isolating DNA from ancient remains is many endeavors together. A third department is also planned highly complicated, as not every shard For example, the Migration Period for the institute. “Since Gray and I have of bone that is thousands of years old that began around 375 A.D., when the a very empirical approach to historical still contains usable genetic material. Huns invaded Eastern Central Europe, research, we need someone to conduct And if it does, the DNA is usually high- and lasted until the 6th century: What that research directly – a historian or an ly degraded and contaminated with the really happened? Archaeological finds archaeologist.” In fact, the underlying genetic traces of bacteria, fungi and from that era are typically rare and idea of the institute’s guiding concept plants that were flushed into the po- have often been subject to vague inter- marks the renaissance of a scientific rous material by rainwater. Later, ar- pretations. Who fled where and merged field: “More than 100 years ago, the chaeologists and museum employees with whom? Genes don’t lie. They can natural sciences and the humanities left traces of their own genetic materi- provide precise data even when all that drifted apart. Here in Jena, we want to al behind on the bone. “Five percent of historians and archaeologists can some- try to bring them back together.” That’s authentic human DNA – that would be

times do is hypothesize. Another exam- precisely what Krause is already doing considered quite a substantial amount Photo: Sven Döring

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» The genome of the Neanderthal differs from that of modern-day humans by 0.1 percent.

in an ancient bone sample,” Krause em- netic variation is shared between mod- evolution, Krause also focuses on his- phasizes. The result is usually just a tiny ern human populations. Genetically torical pathogens and their co-evolu- amount of DNA weighing no more speaking, every form of racism is an ab- tion with humans. Several years ago, he than a few nanograms – billionths of a solute joke. Human populations are used a small number of teeth that were gram. Today, in order to prevent the re- mostly the same. recovered from a London cemetery to searchers from leaving further traces be- reconstruct the genome of Yersinia pes- hind on the material samples, the DNA HITCHING A RIDE ACROSS tis: the pathogen of the Black Death isolation and sequencing preparations THE ATLANTIC that wiped out nearly half of Europe’s are conducted exclusively in clean- population back in the Middle Ages. rooms by staff members wearing sterile Teeth, incidentally, are the best source What traces were left behind in hu- protective clothing. of ancient DNA. As a kind of “time cap- man genes when our ancestors came “Ancient DNA is highly degraded. sule within a time capsule,” they often into contact with pathogens? Along The individual fragments are only about still contain dried blood and nerve cells which routes and with which host did 50 base pairs long, and at the ends of – and with a little bit of luck, even the the plague or the tuberculosis bacillus these fragments, cytosine has often genetic fingerprint of a nasty little travel around the globe? “Tuberculosis been chemically altered into uracil,” germ. The pathogens that cause lepro- already existed on the American conti- Krause explains. “That’s a shame, but sy, tuberculosis and bubonic plague, for nent before Columbus set foot on it,” it’s also a sure sign that the DNA frag- example, like to cling to nerve ends. Krause reports. “Using 1,000-year-old ments being examined are, in fact, an- Apart from ancient DNA and human skeletal samples from Peru, we were able cient genetic material.” After the sample is pulverized, the protein remnants Just 400 milligrams of powder drilled from a bone shard is enough for the researchers to sequence are enzymatically degraded and the re- the genome of the sample (top right). They reconstruct it by using a camera that registers the differently maining genetic material is isolated. stained bases in the DNA fragments (left). At night, the cleanroom laboratories are decontaminated The resulting DNA extract is a complex with UV light to make sure that any trace DNA left behind by the staff is destroyed (bottom right). mixture containing genetic material from various organisms. The ancient human DNA is subsequently fished from that DNA soup – a process that re- quires a “fishing rod.” “And that often takes the form of genetic material of modern-day humans,” reveals Krause, as he talks about a trick that seems sim- ple enough. “One million single-strand- ed DNA fragments fixed on a small glass slide recognize their counterpart in the DNA extract from early Homo sapiens and bind to it.” Now all the researchers have to do is pull the DNA that is bound to the glass slide out of the mix, decode their sequence, and analyze them using bioinformatics methods. The Neanderthal genome, which Johannes Krause helped reconstruct, differs from that of 21st century humans by only 0.1 percent. Modern populations from around the globe have even fewer genetic differences in their DNA. A person’s phenotype – the color of their skin, eyes, hair, and so on – is determined by a few dozen of our

Photos: Frank Vinken (3) 20,000 genes. However, most of our ge-

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» Sometimes paleogenetics can help tell the long-lost story of archaeological finds.

to show that the local pathogen is close- Krause smiles, “which means they can the government of the former German ly related to the tuberculosis pathogen hardly read the ‘molecular clock’.” Fur- Democratic Republic (GDR), which that affects modern-day sea lions. It thermore, ancient mutations also hold tried to counteract these sentiments in likely originated in Africa around just clues about the functions or structures the 1960s by building his home town 5,000 years ago, and finally made its that the pathogens used to adapt to the a socialist planned city that offered way to the indigenous peoples in South human host and that new drugs could 4,000 jobs. With moderate success – America.” How was this possible? “You potentially target. The fact that paleo- “some 50 percent of the inhabitants could say the germ ‘hitchhiked’ across geneticists like Krause know more have since moved away, because a cot- the Atlantic on the sea lions. We as- about the historical pathogens of the ton mill in central Europe doesn’t sume the Native Americans in Peru plague, syphilis, leprosy and tuberculo- make much sense.” contracted the disease by ingesting sis than microbiologists and doctors do Some of his family lived directly in contaminated seal meat.” about their modern “descendants” is a the border region between the two Ger- Just like humans, germs, too, under- bitter truth. All the more reason for manys. Visiting them meant having to go evolutionary changes. By comparing Krause to delve deeper into this re- file an application for a visitation per- the genomes of ancient and modern- search field in Jena. mit and walking past fences and guard day pathogens, scientists can determine dogs. Johannes Krause was ten years old the rate at which these germs undergo REVISITING HIS PERSONAL PAST when the Berlin Wall came down, and mutations. “The leprosy pathogen, for the socialist state into which he had example, changes very slowly, whereas For Johannes Krause, making a new been born suddenly became little more the tuberculosis pathogen changes start in Thuringia also means returning than a controversial chapter in the much more rapidly. This knowledge home. He grew up in Leinefelde in the country’s history books. “A good exam- helps us keep a better lookout for cer- Eichsfeld region in western Thuringia, ple of a social experiment that failed tain pathogens, because germs that which is nestled in a hilly countryside, miserably,” says Krause, who no longer change rapidly also become resistant to surrounded by people with close ties to has any illusions. “If it wasn’t possible antibiotics more quickly.” Medical ex- their homeland. “I like comparing it to even in central Europe, then how is it perts and microbiologists hardly ever the village that Asterix and Obelix supposed to work in other regions of concern themselves with historical come from,” he chuckles. This Catho- the world?” pathogens. Why is that? “They don’t lic enclave in the otherwise Protestant He vividly remembers his first trip make use of the concept of time,” state of Thuringia was too religious for to the nearby town of Göttingen, in the West. The different smells wafting through the supermarket, the yoghurt shelves stocked with a seemingly end- less range of flavors. He had stood in front of the toy shelves in the Karstadt department store with his mouth agape. “Sometimes I think back to the GDR and it somehow reminds me of North Korea.” Not just because of the monot- onous range of available goods, but also because of the drills children had to per- form in kindergarten and in school. His parents weren’t able to pursue their desired careers for having made remarks criticizing the state system. It was therefore also unlikely that Jo- hannes Krause would have been allowed to attend university. However,

Tübingen University maintains a collection of ape skulls and reconstructions to help students visualize the evolution of primates. Photo: Catarina Pietschmann

74 MaxPlanckResearch 4 | 14 Chatting with a close relative: This ape skeleton displayed in the basement of Tübingen University has already been eyed by many generations of students, while the human skulls dating back to the Middle Ages are stored in cardboard boxes, inventoried according to site of the find.

he doesn’t regret having grown up in a socialist state. “My political views are rather left-wing and liberal. Had I grown up in the West, I’m sure my left- wing views would be much more ex- treme. What I learned is that real so- cialism and the human factor simply aren’t compatible.” Yet even a child growing up in the GDR was, first and foremost, just that – a child. Like all young boys, Jo- hannes went through a “dinosaur phase,” treasuring one of the precious few books that dealt with this topic and had been published in Prague at the time. “That was my Bible,” he says, the passion still audible in his voice. “I was able to talk my father into collect- ing fossils with me. We went to all sorts of stone quarries in Thuringia and cracked open rocks.” While he didn’t come across any dinosaurs, he

Photos: Catarina Pietschmann (2) did find hundreds of ammonites that

4 | 14 MaxPlanckResearch 75 Johannes Krause inside the Vindija Cave in Croatia, where the most recent fossilized bone fragments of Neanderthals in central and eastern Europe were discovered. Krause was part of the team headed by Svante Pääbo that used one of the fragments to reconstruct the first genome sequence of a Neanderthal. soon found a new habitat in the fam- nology was being developed at break- his position as a student assistant stip- ily’s garden. Shortly after the fall of the neck speed. “I’ve always been interest- ulated a 19-hour work week, but he Berlin Wall, castles and ruins in the ed in the natural sciences, so why not ended up spending almost all of his border region became his next hunt- biochemistry? I wasn’t even sure what spare time at the laboratory. First he ing grounds. “Overgrown, enchanted that was about, exactly, to be honest,” worked on genetic studies involving fairytale castles that had remained un- he says today. The sheer amount of chimpanzees, then cave bears. The link disturbed for decades – it was just like chemistry soon started to worry him, between genetics and archaeology – eu- in an Indiana Jones movie!” and he was all but ready to voluntari- reka! Johannes Krause had found his re- What would have become of him if ly drop out of his university in Leipzig. search field. the Berlin Wall hadn’t come down? But then he spent a year abroad in In his thesis, he elucidated the famil- “I often asked myself that question. Cork, Ireland. He was riveted by the ial relationships between mammoths Maybe a craftsman like my father? Or lectures delivered by his enthusiastic and African and Asian elephants. His a forest ranger?” He completed his com- genetics professor, and that was when thesis was published in the renowned munity service imposed in lieu of mili- Krause decided “to give biochemistry journal NATURE – pretty cool for a junior tary service at the Eichsfeld Hainich one more chance.” scientist. Krause established a new meth- Werratal nature reserve, and really en- od for reconstructing the entire genome joyed working deep in the woods. But STARTING OUT HIS CAREER AS AN sequence of ancient mitochondrial was that reason enough to spend the ASSISTANT IN LEIPZIG DNA. And then Svante Pääbo offered rest of his life there? No. He had been him the opportunity to help sequence toying with the idea of becoming an ar- When he returned to Leipzig in 2003, the genome of the Neanderthal …. chaeologist or an anthropologist for he contacted a number of laboratories Up until a few years before this, it quite some time, but his career pros- in search of a job as a student assistant. had seemed downright impossible to pects were bleak. Things were to take a That’s how he met Svante Pääbo at the isolate prehistoric DNA, let alone use it rather unexpected turn. MPI for Evolutionary Anthropology. to reconstruct a complete genome. And Around the year 2000 – Johannes The timing couldn’t have been better: the endeavor did, in fact, turn out to be Krause was 20 at the time – the Human Pääbo had only just moved into the extremely challenging. “In the end, we Genome Project made everything and new institute building – there were new succeeded because we always bet on the everyone believe they could soon re- job openings, numerous project ideas, right horse.” lieve mankind from all evil. The bio- and lots of space to put them into prac- The Neanderthal project was com-

tech industry was booming, and tech- tice. Krause’s employment contract for pleted in 2010 with a surprising result, Photo: Private collection

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» Reconstructing the entire genome turned out to be extremely challenging. In the end, we succeeded because we always bet on the right horse.

Teeth are the best source of ancient DNA because they still contain traces of dried blood, nerve cells or the genetic fingerprints of ancient germs, such as the pathogen that causes bubonic plague (right).

namely that a little bit of Neanderthal – dom from their countries of origin dur- Johannes Krause will initially be com- between 2 and 3 percent – can still be ing the colonial era. Important artifacts muting back and forth between the two found today in all people outside Afri- were scattered across the globe or dis- cities, because he will retain his profes- ca. This sparked a range of new proj- appeared in archives, unlabeled. As a sorship in Tübingen for the time being. ects. Krause was able to reconstruct the result, historical traces of entire peo- He has very little spare time. “Do such mitochondrial DNA extracted from a ples were inadvertently eradicated. moments even exist?” he laughs. But tiny knuckle bone discovered in the “But sometimes paleogenetics can also that doesn’t really matter. “By choosing Denisova Cave in the Siberian Altai help tell the long-lost story of certain this career, I am practically living my Mountains. He was able to show that finds.” The indigenous population of hobby.” And this “hobby” can be com- the Denisova hominins were an inde- Australia was uprooted so severely over bined with numerous other activities: he pendent population of the genus Homo, the past 200 years, for example, that enjoys traveling, hiking and fishing, and and that their mitochondrial DNA split the idea of genetically reconstructing tries to go jogging on a regular basis. Oh away from that of the Neanderthals their population structure is currently yes, and not to forget Argentine tango! and modern-day humans more than under discussion. If history has taught us anything, one million years ago. then it is the fact that it repeats itself. Instead of exploring castle ruins and REVIVING A VISIONARY IDEA Sometimes even for the better. It was stone quarries near his hometown, Jo- 17 years ago that the Max Planck Soci- hannes Krause now visits excavation Johannes Krause is passionate about his ety implemented a similarly visionary sites in the Middle East, Indonesia and research. He could talk for hours about idea, which included commissioning Africa, and travels all across Europe. He further history-related questions that Krause’s mentor-to-be, Svante Pääbo, also frequently finds what he’s looking could be answered using genetics. And with setting up the MPI for Evolution- for in museums around the world. Talk- that comes as no surprise, as this young ary Anthropology in Leipzig. Against ing the curators into giving you a few field of research is only just beginning the backdrop of the disastrous actions hundred milligrams of mummy or skel- to unfold. In Jena, he can now put his of anthropologists in the Third Reich, eton bone isn’t always easy. ideas into practice and stake a large this decision – which came 50 years af- The anthropological collections in “claim” for himself. The real work will ter the end of the Nazi dictatorship – Europe in particular are a real Eldora- begin there in early 2015. In the mean- was still a risky step to take. But the do for the researcher – albeit an ethi- time, faster data cables are being in- concept proved to be successful. Had cally questionable one, as many of the stalled in the buildings and a new lab- it not been, Johannes Krause wouldn’t

Photos: MPI for Evolutionary Anthropology (left), NIAID/Creative Commons License 2.0 items on exhibit were looted at ran- oratory will be constructed. be where he is today.

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