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We Use DNA to Predict Our Medical Futures, But it May Have More to Say About the Past


We Use DNA to Predict Our Medical Futures But it May Have More to Say About the Past MIT Technology Review

Source: http://www.technologyreview.com/review/5...

Pääbo’s tale is part hero’s journey and part guidebook to shattering scientific paradigms. He began dreaming about the ancients on a childhood trip to Egypt from his native Sweden. When he grew up, he attended medical school and studied molecular biology, but the romance of the past never faded. As a young researcher, he tried to mummify a calf liver in a lab oven and then extract DNA from it. Most of Pääbo’s advisors saw ancient DNA as a “quaint hobby,” but he persisted through years of disappointing results, patiently awaiting technological innovation that would make the work fruitful. All the while, Pääbo became adept at recruiting researchers, luring funding, generating publicity, and finding ancient bones.

Eventually, his determination paid off: in 1996, he led the effort to sequence part of the Neanderthal mitochondrial genome. (Mitochondria, which serve as cells’ energy packs, appear to be remnants of an ancient single-celled organism, and they have their own DNA, which children inherit from their mothers. This DNA is simpler to read than the full human genome.) Finally, in 2010, Pääbo and his colleagues published the full Neanderthal genome.

That may have been one of the greatest feats of modern biology, yet it is also part of a much bigger story about the extraordinary utility of DNA. For a long time, we have seen the genome as a tool for predicting the future. Do we have the mutation for Huntington’s? Are we predisposed to diabetes? But it may have even more to tell us about the past: about distant events and about the network of lives, loves, and decisions that connects them.

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DNA encodes history:

Such breakthroughs made it possible to answer one of the longest-running questions about Neanderthals: did they mate with humans? There was scant evidence that they had, and Pääbo himself believed such a union was unlikely because he had found no trace of Neanderthal genetics in human mitochondrial DNA. He suspected that humans and Neanderthals were biologically incompatible. But now that the full Neanderthal genome has been sequenced, we can see that 1 to 3 percent of the genome of non-Africans living today contains variations, known as alleles, that apparently originated with Neanderthals. That indicates that humans and Neanderthals mated and had children, and that those children’s children eventually led to many of us. The fact that sub-Saharan Africans do not carry the same Neanderthal DNA suggests that Neanderthal-human hybrids were born just as humans were expanding out of Africa 60,000 years ago and before they colonized the rest of the world. In addition, the way Neanderthal alleles are distributed in the human genome tells us about the forces that shaped lives long ago, perhaps helping the earliest non-Africans adapt to colder, darker regions. Some parts of the genome with a high frequency of Neanderthal variants affect hair and skin color, and the variants probably made the first Eurasians lighter-skinned than their African ancestors.

Ancient DNA will almost certainly complicate other hypotheses, like the ­African-origin story, with its single migratory human band. Ancient DNA also reveals phenomena that we have no other way of knowing about. When Pääbo and colleagues extracted DNA from a few tiny bones and a couple of teeth found in a cave in the Altai Mountains in Siberia, they discovered an entirely new sister group, the Denisovans. Indigenous Australians, Melanesians, and some groups in Asia may have up to 5 percent Denisovan DNA, in addition to their Neanderthal DNA.

In a very short amount of time, a number of ancients have been sequenced by teams all over the world, and the growing library of their genomes has facilitated a new kind of population genetics. What is it that DNA won’t be able to tell us about the past? It may all come down to what happened in the first moments or days after someone’s death. If, for some reason, cells dry out quickly—if you die in a desert or a dry cave, if you are frozen or mummified—post-mortem damage to DNA can be halted, but it may never be possible to sequence DNA from remains found in wet, tropical climates. Still, even working with only the scattered remains that we have found so far, we keep gaining insights into ancient history. One of the remaining mysteries, Pääbo observes, is why modern humans, unlike their archaic cousins, spread all over the globe and dramatically reshaped the environment. What made us different? The answer, he believes, lies waiting in the ancient genomes we have already sequenced.

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