Neanderthal DNA has subtle but significant impact on human traits 
 
 SHARELINES Tweet Hooked on cigarettes? Your Neanderthal DNA might be to blame 
 
 Tweet Neanderthal DNA linked to dozens of human traits and diseases 
 
 
 
 
 
 Since 2010 scientists have known that people of Eurasian origin have inherited anywhere from 1 to 4 percent of their DNA from Neanderthals. 
 
 The discovery spawned a number of hypotheses about the effects these genetic variants may have on the physical characteristics or behavior of modern humans, ranging from skin color to heightened allergies to fat metabolism…generating dozens of colorful headlines including “What your Neanderthal DNA is doing for you” and “Neanderthals are to blame for our allergies” and “Did Europeans Get Fat From Neanderthals?” 
 
 Now, the first study that directly compares Neanderthal DNA in the genomes of a significant population of adults of European ancestry with their clinical records confirms that this archaic genetic legacy has a subtle but significant impact on modern human biology. 
 
 “Our main finding is that Neanderthal DNA does influence clinical traits in modern humans: We discovered associations between Neanderthal DNA and a wide range of traits, including immunological, dermatological, neurological, psychiatric and reproductive diseases,” said John Capra, senior author of the paper “The phenotypic legacy of admixture between modern humans and Neanderthals” published in the Feb. 12 issue of the journal Science. The evolutionary geneticist is an assistant professor of biological sciences at Vanderbilt University. 
 
 Some of the associations that Capra and his colleagues found confirm previous hypotheses. One example is the proposal that Neanderthal DNA affects cells called keratinocytes that help protect the skin from environmental damage such as ultraviolet radiation and pathogens. The new analysis found Neanderthal DNA variants influence skin biology in modern humans, in particular the risk of developing sun-induced skin lesions called keratosis, which are caused by abnormal keratinocytes. 
 
 In addition, there were a number of surprises. For example, they found that a specific bit of Neanderthal DNA significantly increases risk for nicotine addiction. They also found a number of variants that influence the risk for depression: some positively and some negatively. In fact, a surprisingly number of snippets of Neanderthal DNA were associated with psychiatric and neurological effects, the study found. 
 
 “The brain is incredibly complex, so it’s reasonable to expect that introducing changes from a different evolutionary path might have negative consequences,” said Vanderbilt doctoral student Corinne Simonti, the paper’s first author. 
 
 According to the researchers, the pattern of associations that they discovered suggest that today’s population retains Neanderthal DNA that may have provided modern humans with adaptive advantages 40,000 years ago as they migrated into new non-African environments with different pathogens and levels of sun exposure. However, many of these traits may no longer be advantageous in modern environments. 
 
 One example is a Neanderthal variant that increases blood coagulation. It could have helped our ancestors cope with new pathogens encountered in new environments by sealing wounds more quickly and preventing pathogens from entering the body. In modern environments this variant has become detrimental, because hypercoagulation increases risk for stroke, pulmonary embolism and pregnancy complications. 
 
 In order to discover these associations, the researchers used a database containing 28,000 patients whose biological samples have been linked to anonymized versions of their electronic health records. The data came from eMERGE – the Electronic Medical Records and Genomics Network funded by the National Human Genome Research Institute – which links digitized records from Vanderbilt University Medical Center’s BioVU databank and eight other hospitals around the country. 
 
 This data allowed the researchers to determine if each individual had ever been treated for a specific set of medical conditions, such as heart disease, arthritis or depression. Next they analyzed the genomes of each individual to identify the unique set of Neanderthal DNA that each person carried. By comparing the two sets of data, they could test whether each bit of Neanderthal DNA individually and in aggregate influences risk for the traits derived from the medical records. 
 
 “Vanderbilt’s BioVU and the network of similar databanks from hospitals across the country were built to enable discoveries about the genetic basis of disease,” said Capra. “We realized that we could use them to answer important questions about human evolution.” 
 
 According to the evolutionary geneticist, this work establishes a new way to investigate questions about the effects of events in recent human evolution. 
 
 The current study was limited to associating Neanderthal DNA variants with physical traits (phenotypes) included in hospital billing codes, but there is a lot of other information contained in the medical records, such as lab tests, doctors’ notes, and medical images, that Capra is working on analyzing in a similar fashion. 
 
 Additional co-authors are Lisa Bastarache, Dan Roden, Jeffrey Prato and Joshua Denny from Vanderbilt; Benjamin Vernot, David Carrell, David Crosslin, Gail Jarvik and Joshua Akey from the University of Washington; Erwin Bottinger from Mount Sinai School of Medicine; Rex Chisholm from Northwestern University; Scott Hebbring from the Marshfield Clinic; Iftikhar Kullo and Jyotishman Pathak from the Mayo Clinic; Rongling Li from the National Human Genome Research Institute; Marylynn Ritchie and Shefali Verma from Pennsylvania State University; Gerard Tromp from the Geisinger Health System; and William Bush from Case Western Reserve University. 
 
 The research was funded by National Institute of Health grant 5T32EY021453 plus National Human Genome Research Institute grants to members of the eMERGE Network. 
 
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 david.salisbury@vanderbilt.edu ||||| The jawbone of a human who lived between 42,000 and 37,000 years ago showed some Neanderthal features. 
 
 One of the earliest modern humans in Europe had a surprisingly recent Neanderthal ancestor, revealing the two species likely interbred there, according to a new study. 
 
 The Neanderthal relative was so close to the modern human on the family tree that it could have been the equivalent of a great-great-grandparent, the research suggests. 
 
 The finding is revising scientists' understanding of when and where humans and Neanderthals interbred, as it suggests humans had sex with Neanderthals more recently than was previously known. 
 
 The new analysis focuses on a jawbone from Oase 1, an early modern human found in Peștera cu Oase ("Cave with Bones") in southwestern Romania in 2002. Anatomically modern humans populated Europe between 45,000 and 35,000 years ago. Oase 1 lived sometime between 42,000 and 37,000 years ago, making him one of Europe's earliest modern humans. [See Photos of Humanity's Closest Relative] 
 
 DNA extracted from the Oase 1 jawbone showed one of its human ancestors interbred with a Neanderthal. Credit: MPI f. Evolutionary Anthropology/Paabo 
 
 The researchers chose to study Oase 1 because the jaw showed some Neanderthal characteristics. The skull of another early human, Oase 2, found nearby also appeared to have Neanderthal traits. 
 
 The large spans of Neanderthal-like segments in Oase 1's genome indicate that one of his human ancestors interbred with a Neanderthal less than 200 years before he lived. 
 
 "One of Oase 1's fourth- to sixth-degree relatives was a Neanderthal," study co-author Qiaomei Fu, a postdoctoral fellow at the Harvard Medical School Department of Genetics, told Live Science. 
 
 Evidence of interbreeding 
 
 The new finding builds on work led by Svante Pääbo, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and Harvard University's David Reich, which, in 2010, resulted in the first Neanderthal genome ever sequenced. The landmark study answered the long-standing question of whether Homo sapiens and Homo neanderthalensis interbred before humanity's closest relatives went extinct about 35,000 years ago. It showed that interbreeding likely did happen, with Neanderthals contributing roughly 1 to 4 percent of the genomes of all humans living today outside of sub-Saharan Africa. 
 
 In the new analysis, an international team of researchers, including Pääbo and Reich, found that 6 to 9.4 percent of Oase 1's nuclear DNA (located inside a cell's nucleus) was derived from Neanderthals — a higher percentage than has been found in any other modern human genome sequenced so far. 
 
 "The Oase 1 genome has several big Neanderthal-like segments, which is a quite lucky and unexpected thing," Fu said. 
 
 The Neanderthal contribution to the Oase 1 genome is between 2.3- and 3.6-fold larger than the Neanderthal DNA found in the genomes of populations living today outside sub-Saharan Africa and those of four other early modern humans from Russia and Luxembourg whose genomes have been sequenced. One of those ancient humans is even older than Oase 1, Fu said. 
 
 Where the action happened 
 
 The size of Neanderthal segments in human DNA suggest that the two species mated 37,000 to 86,000 years ago. But where and how often they did so have remained a mystery. 
 
 East Asians and Native Americans have more Neanderthal DNA than Europeans, suggesting that more interbreeding happened with the ancestors of eastern non-Africans than with Europeans, the authors wrote in their paper, published today (June 22) in the journal Nature. Until now, there's been little genetic evidence that early humans interbred with Neanderthals once they got to Europe. 
 
 "Analyses of present-day genomes have not yielded any evidence that Neanderthals mixed with modern humans in Europe, despite the fact that Neanderthals were numerous there and cultural interactions between the two groups have been proposed," Fu said. 
 
 However, the new study is changing that: The proximity of a Neanderthal to Oase 1 on the family tree suggests the two species continued interbreeding long after humans first left Africa and entered the Near East. Humans and Neanderthals were mating "later as well, and probably in Europe," the authors wrote. 
 
 However, Oase 1 didn't leave much of a mark on Europe. He shared more gene variants with present-day East Asians and Native Americans than with Europeans, even though he lived in Europe, the researchers said. 
 
 "He may have been a member of an initial early modern human population that interbred with Neanderthals but did not contribute much to later European populations," Fu said. 
 
 Follow Jennifer Abbasi on Twitter. Follow us @livescience, Facebook & Google+. Original article on Live Science.
– It's long been known that the predecessors of modern humans and Neanderthals lived side by side, but it wasn't until 2010 that it was discovered the two species interbred. In fact, as much as 4% of the DNA of modern humans with European or Asian ancestry comes from Neanderthals, reports the Guardian. That intermingling is bound to have consequences, but researchers who've been looking for them were surprised to find a dozen traits specifically linked to Neanderthal genetic variants—including risk for nicotine addiction, artery thickening, heart attack, and depression. Researchers arrived at their conclusions, published in the journal Science, after cross-referencing Neanderthal DNA with a database of 28,000 people of European ancestry that pulls together biological samples and electronic health records. "The brain is incredibly complex, so it's reasonable to expect that introducing changes from a different evolutionary path might have negative consequences," lead author Corinne Simonti says in a Vanderbilt News statement. Case in point: The researchers found Neanderthal DNA increases blood clotting, which would have helped seal wounds more speedily; but for modern man, hypercoagulation ups the risk of miscarriage, stroke, and more, reports Live Science. Oh, and the popular idea that Neanderthal DNA influences skin tone is probably bunk, the researchers add, noting skin color differences likely emerged much more recently. (Sex with Neanderthals may also explain modern allergies.)