What Did Neanderthals Leave to Modern Humans? Some Surprises

At Vanderbilt University, John Anthony Capra, an evolutionary genomics professor, has been combining high-powered computation and a medical records databank to learn what a Neanderthal heritage — even a fractional one — might mean for people today.
We spoke for two hours when Dr. Capra, 35, recently passed through New York City. An edited and condensed version of the conversation follows.

-Let’s begin with an indiscreet question. How did contemporary people come to have Neanderthal DNA on their genomes?

-He replied: “we hypothesize that roughly 50,000 years ago, when the ancestors of modern humans migrated out of Africa and into Eurasia, they encountered Neanderthals. Mating must have occurred then, and later.”

One reason we deduce this is because the descendants of those who remained in Africa — present day Africans — don’t have Neanderthal DNA.

What does that mean for people who have it?
At my lab, we’ve been doing genetic testing on the blood samples of 28,000 patients at Vanderbilt and eight other medical centers across the country. Computers help us pinpoint where on the human genome this Neanderthal DNA is, and we run that against information from the patients’ anonymized medical records. We’re looking for associations.



What we’ve been finding is that Neanderthal DNA has a subtle influence on risk for disease. It affects our immune system and how we respond to different immune challenges. It affects our skin. You’re slightly more prone to a condition where you can get scaly lesions after extreme sun exposure. There’s an increased risk for blood clots and tobacco addiction.

To our surprise, it appears that some Neanderthal DNA can increase the risk for depression; however, there are other Neanderthal bits that decrease the risk. Roughly 1 to 2 percent of one’s risk for depression is determined by Neanderthal DNA. It all depends on where on the genome it’s located.

Was there ever an upside to having Neanderthal DNA?
It probably helped our ancestors survive in prehistoric Europe. When humans migrated into Eurasia, they encountered unfamiliar hazards and pathogens. By mating with Neanderthals, they gave their offspring needed defenses and immunities.



That trait for blood clotting helped wounds close up quickly. In the modern world, however, this trait means greater risk for stroke and pregnancy complications. What helped us then doesn’t necessarily now.

Did you say earlier that Neanderthal DNA increases susceptibility to nicotine addiction? Yes. Neanderthal DNA can mean you’re more likely to get hooked on nicotine, even though there were no tobacco plants in archaic Europe.

We think this might be because there’s a bit of Neanderthal DNA right next to a human gene that’s a neurotransmitter implicated in a generalized risk for addiction. In this case and probably others, we think the Neanderthal bits on the genome may serve as switches that turn human genes on or off.

Aside from the Neanderthals, do we know if our ancestors mated with other hominids? We think they did. Sometimes when we’re examining genomes, we can see the genetic afterimages of hominids, which haven’t even been identified yet.




MORE REPORTING ON HUMAN ORIGINS
A few years ago, the Swedish geneticist Svante Pääbo received an unusual fossilized bone fragment from Siberia. He extracted the DNA, sequenced it and realized it was neither human nor Neanderthal. What Pääbo found was a previously unknown hominid he named Denisovan, after the cave where it had been discovered. It turned out that Denisovan DNA can be found on the genomes of modern Southeast Asians and New Guineans.

Have you long been interested in genetics?
Growing up, I was very interested in history, but I also loved computers. I ended up majoring in computer science at college and going to graduate school in it; however, during my first year in graduate school, I realized I wasn’t very motivated by the problems that computer scientists worked on.

Fortunately, around that time — the early 2000s — it was becoming clear that people with computational skills could have a big impact in biology and genetics. The human genome had just been mapped. What an accomplishment! We now had the code to what makes you, you, and me, me. I wanted to be part of that kind of work.

So I switched over to biology. And it was there that I heard about a new field where you used computation and genetics research to look back in time — evolutionary genomics.



There may be no written records from prehistory, but genomes are a living record. If we can find ways to read them, we can discover things we couldn’t know any other way.

Not long ago, the two top editors of The New England Journal of Medicine published an editorial questioning “data sharing,” a common practice where scientists recycle raw data other researchers have collected for their own studies. They labeled some of the recycling researchers, “data parasites.” How did you feel when you read that?
I was upset. The data sets we used were not originally collected to specifically study Neanderthal DNA in modern humans. Thousands of patients at Vanderbilt consented to have their blood and their medical records deposited in a “biobank” to find genetic diseases.

Three years ago, when I set up my lab at Vanderbilt, I saw the potential of the biobank for studying both genetic diseases and human evolution. I wrote special computer programs so that we could mine existing data for these purposes.

That’s not being a “parasite.” That’s moving knowledge forward. I suspect that most of the patients who contributed their information are pleased to see it used in a wider way.

What has been the response to your Neanderthal research since you published it last year in the journal Science?

Some of it’s very touching. People are interested in learning about where they came from. Some of it is a little silly. “I have a lot of hair on my legs — is that from Neanderthals?”

But I received racist inquiries, too. I got calls from all over the world from people who thought that since Africans didn’t interbreed with Neanderthals, this somehow justified their ideas of white superiority.

It was illogical. Actually, Neanderthal DNA is mostly bad for us — though that didn’t bother them.

As you do your studies, do you ever wonder about what the lives of the Neanderthals were like?
It’s hard not to. Genetics has taught us a tremendous amount about that, and there’s a lot of evidence that they were much more human than apelike.

They’ve gotten a bad rap. We tend to think of them as dumb and brutish. There’s no reason to believe that. Maybe those of us of European heritage should be thinking, “Let’s improve their standing in the popular imagination. They’re our ancestors, too.’”
Source: Claudia Dreifus

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Are we closer than ever to a timeline for human evolution?

Dating when our ancestors split from Neanderthals and other relatives has long been a puzzle, but DNA advances are making our evolutionaNeanderthalsy journey clearer

Anthropologists and geneticists had a problem. And the farther back in time they looked, the bigger the problem became.

For the past several years, there have been two main genetic methods to date evolutionary divergences - when our ancestors split from Neanderthals, chimpanzees, and other relatives. The problem was, the results of these methods differed by nearly two-fold.

By one estimate, modern humans split from Neanderthals roughly 300,000 years ago. By the other, the split was closer to 600,000 years ago. Likewise, modern humans and chimps may have diverged around 6.5 or 13 million years ago.

Puzzled by this wild disagreement, researchers with diverse expertise have been studying it from different angles. Their combined discoveries, recently reviewed, here, have shed light on how genetic differences accumulate over time and have advanced methods of genetic dating.



And if you’re in suspense, yes, they’ve also pinned down important events in our evolutionary timeline. Everyone alive today seems to share ancestors with each other just over 200,000 years ago and with Neanderthals between 765,000-550,000 years ago.

Dating with the molecular clock
Go back in time and you’ll find a population of Homo sapiens who were the ancestors of everyone living today. Go back farther and our lineage meets up with Neanderthals, then chimps, and eventually all primates, mammals, and life.
In order to date these evolutionary splits, geneticists have relied on the molecular clock - the idea that genetic mutations accumulate at a steady rate over time. Specifically this, concerns mutations that become neutral substitutions, or lasting changes to letters of the genetic code that do not affect an organism’s chances of surviving and reproducing.



If such mutations arise clocklike, then calculating the time since two organisms shared common ancestors should be as easy as dividing the number of genetic differences between them by the mutation rate - the same way that dividing distance by speed gives you travel time.

But you need to know the rate.
For decades, anthropologists used fossil calibration to generate the so-called phylogenetic rate (a phylogeny is a tree showing evolutionary relationships). They took the geologic age of fossils from evolutionary branch points and calculated how fast mutations must have arisen along the resulting lineages.

For example, the earliest fossils on the human branch after our split with chimps are identified by the fact that they seem to have walked on two legs; bipedalism is
the first obvious difference that distinguishes our evolutionary lineage of hominins from that of chimps. These fossils are 7-6 million years old, and therefore the chimp-human split should be around that age. Dividing the number of genetic differences between living chimps and humans by 6.5 million years provides a mutation rate.

Determined this way, the mutation rate is 0.000000001 (or 1x10-9) mutations per DNA base pair per year. Applied to genomes with 6 billion base pairs, that means over millions of years of chimp and human evolution, and there have been on average six changes to letters of the genetic code per year.

Why archaeology needs to come out of the cave and into the digital age
This rate can be used to date evolutionary events that are not evident from fossils, such as the spread of modern humans out of Africa.



But genetic dating got messy in 2010, when improvements to DNA sequencing allowed researchers to determine the number of genetic differences between parents and their children. Known as pedigree analysis, this provides a more direct measurement of the current mutation rate within one generation, rather than an average over millions of years.

Pedigree analysis counts 60-some mutations every generation; that converts to a rate approximately half the phylogenetic estimate—meaning evolutionary events would be twice as old.

The erratic molecular clock
Resolving this disagreement propelled researchers to reassess and revise their starting assumptions: How accurately were they counting the small number of differences between genomes of parents and children? Were fossils assigned to the correct branches of the evolutionary tree? And above all, how constant is the molecular clock?

It turns out that among primates, the molecular clock varies significantly by species, sex, and mutation type. A recent study found that New World monkeys (i.e. monkeys of the Americas like marmosets and squirrel monkeys) have substitution rates about 64% higher than apes (including humans). Within apes, rates are about 7% higher in gorillas and 2% higher in chimpanzees, compared to humans.



But even among humans, mutation rates differ, particularly between the sexes with age. As fathers get older, they gain about one additional mutation per year in the DNA they can pass on to children. Mothers, on the other hand, accumulate considerably fewer mutations with each passing year.

These species and sex differences make sense when you consider how mutations form. Most heritable mutations occur from mistakes when DNA copies itself in the germline, or cells leading to eggs and sperm. The number of times germline DNA has to copy itself depends on developmental and reproductive variables including age at puberty, age at reproduction, and the process of sperm production.
These traits vary across primates today and certainly varied over primate evolution.

For instance, average generation times are six years for New World monkeys, 19 years for gorillas, 25 years for chimps, and 29 years for humans.

And those extra mutations as fathers get older? Sperm are produced continuously after puberty, so sperm made later in life are the result of more rounds of DNA replication and opportunities for replication errors. In contrast, a mother’s stock of eggs is formed by birth. The small increase with maternal age could be due to mutations from DNA damage, rather than replication errors.

Ways forward for dating backwards
It’s now clear that one mutation rate cannot determine the dates for all divergences relevant to human evolution. However, researchers can secure the timeline for important evolutionary events by combining new methods of genetic dating with fossils and geologic ages.

Innovative computational methods have incorporated reproductive variables into calculations. By taking into account ages of reproduction in both sexes, age of male puberty, and sperm production rates, researchers have estimated split times that accord with the fossil record.



Another new approach has analyzed mutations that are mainly independent of DNA replication. It seems that certain classes of mutations, related to DNA damage, do behave more clocklike.

And some researchers have focused on ancient DNA. Comparing human fossils from the past 50,000 years to humans today, suggests a mutation rate that agrees with pedigree analysis.

At least one evolutionary split was pinned down in 2016, after ancient DNA was extracted from 430,000 year-old hominin fossils from ‘Sima de los Huesos’, Spain. The Sima hominins looked like early members of the Neanderthal lineage based on morphological similarities. This hypothesis fit the timing of the split between Neanderthals and modern humans based on pedigree analysis (765,000-550,000 years ago), but did not work with the phylogenetic estimate (383,000-275,000 years ago).
Where do the Sima hominins belong on our family tree? Were they ancestors of both Neanderthals and modern humans, just Neanderthals, or neither?

DNA answered this definitively. The Sima hominins belong to the Neanderthal branch after it split with modern humans. Moreover, the result provides a firm time point in our family tree, suggesting that the pedigree rate works for this period of human evolution.

Neanderthals and modern humans likely diverged between 765,000-550,000 years ago. Other evolutionary splits may soon be clarified as well, thanks to advances brought about by the mutation rate debates. Someday soon, when you see a chimp, you may be able to salute your great, great… great grandparent, with the correct number of “greats.”
Source: Biology News

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Jersey was a must-see tourist destination for Neanderthals for over 100,000 years, showing a nomad behavior

New research led by the University of Southampton shows Neanderthals kept coming back to a coastal cave site in Jersey from at least 180,000 years ago until around 40,000 years ago.

Neanderthals kept coming back to a coastal cave site in Jersey from at least 180,000 years ago until around 40,000 years ago, researchers reported. As part of a re-examination of La Cotte de St Brelade and its surrounding landscape, archaeologists have taken a fresh look at artefacts and mammoth bones originally excavated from within the site's granite cliffs in the 1970s.

As part of a re-examination of La Cotte de St Brelade, and its surrounding landscape, archaeologists from Southampton, together with experts from three other universities and the British Museum have taken a fresh look at artefacts and mammoth bones originally excavated from within the site's granite cliffs in the 1970s. Their findings are published in the journal Antiquity.




The researchers matched types of stone raw material used to make tools to detail mapping of the geology of the sea bed, and studied in detail how they were made, carried and modified. This helped reconstruct a picture of what resources were available to Neanderthals over tens of thousands of years -- and where they were travelling from.
Lead author Dr. Andy Shaw of the Centre for the Archaeology of Human Origins (CAHO) at the University of Southampton said: "La Cotte seems to have been a special place for Neanderthals. They kept making deliberate journeys to reach the site over many, many generations. We can use the stone tools they left behind to map how they were moving through landscapes, which are now beneath the English Channel. 180,000 years ago, as ice caps expanded and temperatures plummeted, they would have been exploiting a huge offshore area, inaccessible to us today."

Previous research focused on particular levels in the site where mammoth bones are concentrated, but this new study took a longer-term perspective, looking at how Neanderthals used it and explored the surrounding landscape for over 100,000 years.
The team, including academics from the British Museum, University College London (UCL) and the University of Wales found that Neanderthals kept coming back to this particular place, despite globally significant changes in climate and landscape. During glacial phases (Ice Ages), they travelled to the site over cold, open landscapes, now submerged under the sea. They kept visiting as the climate warmed up and Jersey became a striking highpoint in a wide coastal plain connected to France.



Dr. Beccy Scott of the British Museum added: "We're really interested in how this site became 'persistent' in the minds of early Neanderthals. You can almost see hints of early mapping in the way they are travelling to it again and again, or certainly an understanding of their geography. But specifically what drew them to Jersey so often is harder to tease out. It might have been that the whole Island was highly visible from a long way off -- like a way marker -- or people might have remembered that shelter could be found there, and passed that knowledge on."

Paper author Dr. Matt Pope, of the Institute of Archaeology at UCL, agrees: "La Cotte de St Brelade is probably the most important Neanderthal site in northern Europe and could be one of the last known places that Neanderthals survived in the region. It was certainly as important to them as it is to us, as we try and understand how they thrived and survived for 200,000 years.

"With new technology we have been able to reconstruct the environment of the La Cotte Neanderthals in a way earlier researchers couldn't. Our project has really put Neanderthal back into the landscape, but emphasized how significant the changes in climate and landscape have been since then."

Project leader Professor Clive Gamble, of CAHO at the University of Southampton, comments: "Jersey is an island that endures, summed up by the granite cliffs of St Brelade's Bay. The elements which led to Neanderthals coming back for so many thousands of years show how this persistence is deep rooted in Jersey's past. Our project has shown that more unites the past with the present than separates. We are not the only humans to have coped successfully with major environmental changes. Let's hope we are not the last."

The team's work was undertaken as part of the 'Crossing the Threshold' project led by Professor Clive Gamble and Dr. John McNabb at the University of Southampton, together with UCL and the British Museum. The research was funded by the Arts and Humanities Research Council and looks at major changes in how early humans used places from 400,000 years ago.

Story Source: University of Southampton

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Who are human's real ancestors?

Neanderthals became extinct about 40,000 years ago but contributed on average one to three percent to the genomes of present-day Eurasians. Researchers have now analyzed DNA from a 37,000 to 42,000-year-old human mandible from Oase Cave in Romania and have found that six to nine percent of this person's genome came from Neanderthals, more than any other human sequenced to date. Because large segments of this individual's chromosomes are of Neanderthal origin, a Neanderthal was among his ancestors as recently as four to six generations back in his family tree. This shows that some of the first modern humans that came to Europe mixed with the local Neanderthals.

All present-day humans who have their roots outside sub-Saharan Africa carry one to three percent of Neanderthal DNA in their genomes. Until now, researchers have thought it most likely that early humans coming from Africa mixed with Neanderthals in the Middle East around 50,000 to 60,000 years ago, before spreading into Asia, Europe and the rest of the world. However, radiocarbon dating of remains from sites across Europe suggests that modern humans and Neanderthals both lived in Europe for up to 5,000 years and that they may have interbred there, too.

In 2002, a 40,000-year-old jawbone was found by cavers in Oase Cave in south-western Romania and the site was subsequently studied by an international team led by the researchers of the Emil Racovita Institute of Speleology in Romania. Researchers from the Max Planck Institute for Evolutionary Anthropology (Germany), Harvard Medical School (USA), and the Key Laboratory of Vertebrate Evolution and Human Origins in Beijing (China) have now analyzed DNA from this fossil, which is one of the earliest modern-human remains found in Europe. They estimate that five to 11 percent of the genome preserved in the bone derives from a Neanderthal ancestor, including exceptionally large segments of some chromosomes. By estimating how lengths of DNA inherited from an ancestor shorten with each generation, the researchers estimated that the man had a Neanderthal ancestor in the previous four to six generations.

"The data from the jawbone imply that humans mixed with Neanderthals not just in the Middle East but in Europe as well" says Qiaomei Fu, one of the lead researchers of the study. "Interestingly, the Oase individual does not seem to have any direct descendants in Europe today," says David Reich from Harvard Medical School who coordinated the population genetic analyses of the study. "It may be that he was part of an early migration of modern humans to Europe that interacted closely with Neanderthals but eventually became extinct."

"It is such a lucky and unexpected thing to get DNA from a person who was so closely related to a Neanderthal" comments Svante Paabo from the Max Planck Institute for Evolutionary Anthropology who led the study. "I could hardly believe it when we first saw the results." "We hope that DNA from other human fossils that predate the extinction of Neanderthals will help reconstruct the interactions between Neanderthals and modern humans in even more detail," says Mateja Hajdinjak, another key researcher involved in the study.

"When we started the work on Oase site, everything was already pointing to an exceptional discovery," remembers Oana Moldovan, the Romanian researcher who initiated the systematic excavation of the cave in 2003. "But such discoveries require painstaking research to be confirmed," adds Silviu Constantin, her colleague who worked on dating of the site. "We have previously shown that Oase is indeed the oldest modern human in Europe known so far, and now this research confirms that the individual had a Neanderthal ancestor. What more could we wish for?"

Story Source:

The above post is reprinted from materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.

Journal Reference:

Qiaomei Fu, Mateja Hajdinjak, Oana Teodora Moldovan, Silviu Constantin, Swapan Mallick, Pontus Skoglund, Nick Patterson, Nadin Rohland, Iosif Lazaridis, Birgit Nickel, Bence Viola, Kay Prüfer, Matthias Meyer, Janet Kelso, David Reich, Svante Pääbo. An early modern human from Romania with a recent Neanderthal ancestor. Nature, 2015; DOI: 10.1038/nature14558

Photo: Credit: MPI f. Evolutionary Anthropology/ Paabo