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Where DNA Degrades, Proteins Might Persist. So Scientists Are Looking to Fill in Early Human History Using Some Very Old Amino Acids

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Where DNA Degrades, Proteins Might Persist. So Scientists Are Looking to Fill in Early Human History Using Some Very Old Amino Acids ANCIENT PROTEINS TELL THEIR TALES Where DNA degrades, proteins might persist. So scientists are looking to fill in early human history using some very old amino acids. BY MATTHEW WARREN ome time in the past 160,000 years or retreated again, and all that was left behind so, the remains of an ancient human was a bit of jawbone with some teeth. The ended up in a cave high on the Tibetan bone gradually became coated in a mineral SKULL ADAPTED ADAPTED SKULL Plateau in China. Perhaps the individ- crust, and the DNA from this ancient ancestor Sual died there, or parts were taken there by was lost to time and weather. But some signal its kin or an animal scavenger. In just a few from the past persisted. years, the flesh disappeared and the bones Deep in the hominin’s teeth, proteins lin- started to deteriorate. Then millennia dripped gered, degraded but still identifiable. When HOMO FLORESIENSIS FROM WORLD HISTORY ARCHIVE/ALAMY HISTORY FROM WORLD by. Glaciers retreated and then returned and scientists analysed them earlier this year, ©2019 Spri nger Nature Li mited. All ri ghts reserved. 27 JUNE 2019 | VOL 570 | NATURE | 433 NEWS FEATURE they detected collagen, a structural support from ancient fossils has transformed scientists’ the types of animal they came from. In this protein found in bone and other tissues. And understanding of human evolution. Analysis specific approach, called zooarchaeology by in its chemical signature was a single amino- of the similarities and differences in the DNA mass spectrometry or ZooMS, researchers ana- acid variant that isn’t present in the collagen of of different hominin groups has allowed lyse one kind of collagen. The mass of collagen’s modern humans or Neanderthals — instead, researchers to map out the tangled family components differs in various groups and spe- it flagged the jawbone as belonging to a mem- tree in a way that was previously not possible. cies, providing a characteristic fingerprint that ber of the mysterious hominin group called And genetic material has led to some major allows researchers to identify the bone’s source. Denisovans1. The discovery of a Denisovan finds, such as the discovery of Denisovans in ZooMS was used in a 2016 paper3 to identify in China was a major landmark. It was the the first place. one hominin bone among thousands of frag- first individual found outside Denisova Cave But glaring gaps remain in that picture. DNA ments from Denisova Cave — a bone that DNA in Siberia, where all other remains of its kind has been sequenced from just three groups of analysis would later show belonged to a hybrid had previously been identified. And the site’s hominin: Neanderthals, Denisovans and Homo individual, nicknamed Denny, with a Nean- location on the Tibetan Plateau — more than sapiens, mostly from specimens that are less derthal mother and a Denisovan father. Even 3,000 metres above sea level — suggested that than 100,000 years old (a notable exception is with that result alone, ancient protein analysis Denisovans had been able to live in very cold, a pair of 430,000-year-old early Neanderthals had already substantially expanded our view low-oxygen environments. from Spain2). Go a few hundred thousand years of human evolution, says population geneticist But the finding also marked another mile- further back, and things get much murkier. Pontus Skoglund at the Francis Crick Institute stone: it was the first time that an ancient hom- This was a time period when a lot of exciting in London. Katerina Douka, an archaeologist inin had been identified using only proteins. things were happening, says Frido Welker, a at the Max Planck Institute for the Science of It is one of the most striking discoveries yet molecular anthropologist at the University of Human History in Jena, Germany, is now using for the fledgling field of palaeoproteomics, in Copenhagen. It’s when Denisovans and Nean- the technique to search through 40,000 uniden- which scientists analyse ancient proteins to derthals branched off from the lineage that tified bone fragments from Asia in the hope of answer questions about the history and evolu- would become modern humans, for example. uncovering more ancient hominins. tion of humans and other animals. Proteins, But it remains a hazy part of human history. which stick around in fossils for much longer Researchers don’t know, for instance, whether than DNA does, could allow scientists to the ancient hominin Homo heidelbergensis, explore whole new eras of prehistory and use which lived around 700,000–200,000 years “I THINK THAT YOU molecular tools to examine bones from a much ago, was an ancestor of both H. sapiens and broader part of the world than is currently Neanderthals or part of only the Neanderthal CAN BASICALLY possible, according to the field’s proponents. branch, as some have suggested. “A lot of that Previously, scientists had recovered proteins happens beyond the reach of ancient DNA,” UNLOCK THE from 1.8-million-year-old animal teeth and a says Welker. 3.8-million-year-old eggshell. Now, they hope Go back one million years or more, and WHOLE OF THE that palaeoproteomics could be used to provide things get even less clear. H. erectus, for exam- insights about other ancient hominin fossils ple, first emerged in Africa around 1.9 million HUMAN TREE.” that have lost all traces of DNA — from Homo years ago, but without DNA evidence, it erectus, which roamed parts of the world from remains uncertain exactly how it is related to about 1.9 million to 140,000 years ago, to Homo later hominins, including H. sapiens. But ZooMS paints a picture only in broad floresiensis, the diminutive ‘hobbit’ species that Ancient DNA has also left geographical brushstrokes. Once a bone is identified as lived in Indonesia as recently as 60,000 years blind spots. DNA degrades faster in warm belonging to a hominin, for example, other ago. By looking at variations in these proteins, environments, so although a 100,000-year-old techniques are needed to delve deeper. So oth- scientists hope to answer long-standing ques- specimen found in a cold Siberian cave might ers have turned to shotgun proteomics, which tions about the evolution of ancient human still harbour genetic material, a fossil that has aims to identify all the protein sequences in a groups, such as which lineages were direct spent that long in the heat of Africa or south- sample — its proteome. The composition of ancestors of Homo sapiens. “I think that you can east Asia generally will not. As a result, little the proteome depends on the kind of tissue basically unlock the whole of the human tree,” is known about the genetics of even relatively being examined, but will often include various says Matthew Collins, a bioarchaeologist at the recent hominins from these regions, such as forms of collagen. This method spits out thou- University of Copenhagen who has been at the H. floresiensis. sands of signals, which makes it much more forefront of the field since the 1980s, when it Now researchers are hoping that protein informative than ZooMS, says Douka, but also consisted of just a handful of researchers. analysis might begin to fill in some of those trickier to interpret. By matching these signals blanks. The idea is not new: as early as the to known sequences in databases, researchers A COMING OF AGE 1950s, researchers had reported finding amino can identify the exact sequences of collagen or Despite the excitement, some argue that acids in fossils. But for a long time, the technol- other proteins in their sample. researchers could struggle to paint a definitive ogy needed to sequence ancient proteins just Scientists can then compare this newly picture of human history from the information didn’t exist. “For most of my career, I honestly, determined protein sequence to the same that researchers can get out of proteins, which genuinely believed that we would not be able to protein from other hominin groups, looking is limited compared with that obtainable from recover ancient protein sequences,” says Collins. for similarities and differences in individual DNA. And many worry that palaeoproteom- That changed in the 2000s, after researchers amino acids that will help to place the homi- ics in general might be susceptible to spurious realized that mass spectrometry — a technique nin on the family tree. This is similar to how results, stemming from issues such as con- used to study modern proteins — could also be ancient-DNA researchers look at single-letter tamination. “You see very good research, and applied to ancient proteins. Mass spectrometry variations in genetic sequences. then you see people that publish things that essentially involves breaking down proteins are just very strange, because they don’t think into their constituent peptides (short chains FILLING IN THE GAPS critically about the methods,” says Philipp of amino acids) and analysing their masses to Although researchers had used protein Stockhammer, an archaeologist at the Ludwig deduce their chemical make-up. analysis alongside ancient DNA sequencing Maximilian University of Munich in Germany. Researchers have used this method to sift before4, the Tibetan Denisovan was the first Over the past two decades, DNA retrieved through hundreds of bone fragments to identify ancient hominin for which proteins alone 434 | NATURE | VOL 570 | 27 JUNE 2019 ©2019 Spri nger Nature Li mited. All ri ghts reserved. ©2019 Spri nger Nature Li mited. All ri ghts reserved. FEATURE NEWS were analysed — and others could soon HOMO DENISOVAN follow (see ‘Getting fossils to speak’). A look FLORESIENSIS TOOTH AND at the protein sequences from H.
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