Neanderthals gave us a selection of disease genes - [Journal article]

(BBC News, 30th January 2014) - Gene types that influence disease in people today were picked up through interbreeding with Neanderthals, a major study in Nature journal suggests.

Journal article: Resurrecting Surviving Neandertal Lineages from Modern Human Genomes

They passed on variants involved in type 2 diabetes, Crohn's disease and - curiously - smoking addiction.

Genome studies reveal that our species (Homo sapiens) mated with Neanderthals after leaving Africa.

But it was previously unclear what this Neanderthal DNA did and whether there were any implications for human health.

Between 2% and 4% of the genetic blueprint of present-day non-Africans came from Neanderthals.

By screening the genomes of 1,004 modern humans, Sriram Sankararaman and his colleagues identified regions bearing the Neanderthal versions of different genes.

That a gene variant associated with a difficulty in stopping smoking should be found to have a Neanderthal origin is a surprise.

It goes without saying that there is no suggestion our evolutionary cousins were puffing away in their caves.

Instead, the researchers argue, this mutation may have more than one function, so the modern effect of this marker on smoking behaviour may be one impact it has among several.

Researchers found that Neanderthal DNA is not distributed uniformly across the human genome, instead being commonly found in regions that affect skin and hair.

This suggests some gene variants provided a rapid way for modern humans to adapt to the new cooler environments they encountered as they moved into Eurasia. When the populations met, Neanderthals had already been adapting to these conditions for several hundred thousand years.

The stocky hunters once covered a range stretching from Britain to Siberia, but went extinct around 30,000 years ago as Homo sapiens was expanding from an African homeland.

Neanderthal ancestry was found in regions of the genome linked to the regulation of skin pigmentation.

"We found evidence that Neanderthal skin genes made Europeans and East Asians more evolutionarily fit," said Benjamin Vernot, from the University of Washington, co-author of a separate study in Science journal.

Genes for keratin filaments, a fibrous protein that lends toughness to skin, hair and nails, were also enriched with Neanderthal DNA. This may have helped provide the newcomers with thicker insulation against cold conditions, the scientists suggest.

"It's tempting to think that Neanderthals were already adapted to the non-African environment and provided this genetic benefit to (modern) humans," said Prof David Reich, from Harvard Medical School, co-author of the paper in Nature.

But other gene variants influenced human illnesses, such as type 2 diabetes, long-term depression, lupus, billiary cirrhosis - an autoimmune disease of the liver - and Crohn's disease. In the case of Crohn's, Neanderthals passed on different markers that increase and decrease the risk of disease.

Asked whether our ancient relatives actually suffered from these diseases too, or whether the mutations in question only affected the risk of illness when transplanted to a modern human genetic background, Mr Sankararaman said: "We don't have the fine knowledge of the genetics of Neanderthals to answer this," but added that further study of their genomes might shed light on this question.

Joshua Akey, from the University of Washington, an author of the Science publication, added: "Admixture happened relatively recently in evolutionary terms, so you wouldn't expect all the Neanderthal DNA to have been washed away by this point.

"I think what we're seeing to a large extent is the dying remains of this extinct genome as it is slowly purged from the human population."

However, some regions of our genomes were discovered to be devoid of Neanderthal DNA, suggesting that certain genes had such harmful effects in the offspring of modern human-Neanderthal pairings that they have indeed been flushed out actively and rapidly through natural selection.

"We find that there are large regions of the genome where most modern humans carry little or no Neanderthal ancestry," Mr Sankararaman told BBC News.

"This reduction in Neanderthal ancestry was probably due to selection against genes that were bad - deleterious - for us."

The Neanderthal-deficient regions encompass genes that are specifically expressed in the testes, and on the X (female sex) chromosome.

This suggests that some Neanderthal-modern human hybrids had reduced fertility and in some cases were sterile.

"It tells us that when Neanderthals and modern humans met and mixed, they were at the very edge of being biologically compatible," said Prof Reich.

Another genome region that lacked Neanderthal genes includes a gene called FOXP2, which is thought to play an important role in human speech.

Joshua Akey said his team's results were compatible with there having been multiple pulses of interbreeding between modern humans and Neanderthals.

Evidence of interbreeding among early Hominins - [Journal article]

http://digitaljournal.com

(Iflscience.com, 25, November 2013) - The evolutionary tree for modern humans is a bit of a mess - humans haven’t had a close relative on this planet for over 10,000 years, but there used to be several other closely related species living at the same time.

Genetic analyses on bone fragments from Neanderthals and Denisovans has given us new insight into our not-so-distant evolutionary past. The results indicate that not only did Denisovans and Neanderthals interbreed with modern Homo sapiens, but they also mated with an unidentified fourth hominin group. This information was presented to evolutionary geneticists last week for a meeting of the Royal Society.

Neanderthals emerged about 200,000 years ago and remains have been found throughout Europe, stretching into central Asia. While Neanderthals weren’t as cognitively advanced as Homo sapiens who emerged around the same time, they were probably the first hominins known to wear clothing, bury dead, and form languages. It has been traditionally thought that the last common ancestor of Homo sapiens and Neanderthals existed around 400,000 years ago, though new research suggests it could have been earlier.

Denisovans are an extinct group of hominins that are part of our evolutionary lineage. Our knowledge of them comes from bone fragments found in a cave that date back about 30,000-50,000 years. Though genetic analysis had been done a couple years ago, the results weren’t really clear. New techniques have yielded much more complete genetic sequences and two new studies have released different yet related results.

There is evidence of certain populations of humans alive today getting as much as 4% of their DNA from Denisovans, though there is some debate surrounding it. Additionally, there are people with ancestries outside of Africa that could have gotten about 2% of their genomes from Neanderthals, though there is some speculation with this as well.

Right now, the identity of this fourth early human group remains a mystery. They could have come from Asia, but that has not yet been made certain. Future research will hopefully identify this unknown population and help us better understand all of the different evolutionary inputs that make us who we are.

Related references:

Journal article: A Draft Sequence of the Neandertal Genome

Journal article: A High-Coverage Genome Sequence from an Archaic Denisovan Individual

Neanderthals ... They're Just Like Us?

Photograph by Joe McNally, National Geographic
 "Come at me bro"

(National Geographic.com, 12, Oct 2012) - Well, not exactly. But new discoveries have had a surprisingly humanizing effect.

The Neanderthals are both the most familiar and the least understood of all our fossil kin.

For decades after the initial discovery of their bones in a cave in Germany in 1856 Homo neanderthalensis was viewed as a hairy brute who stumbled around Ice Age Eurasia on bent knees, eventually to be replaced by elegant, upright Cro-Magnon, the true ancestor of modern Europeans.

Science has long since killed off the notion of that witless caveman, but Neanderthals have still been regarded as quintessential losers—a large-brained, well-adapted species of human that went extinct nevertheless, yielding the Eurasian continent to anatomically modern humans, who began to migrate out of Africa some 60,000 years ago.

Lately, the relationship between Neanderthals and modern humans has gotten spicier.

According to a new study that analysed traces of Neanderthal DNA in present-day humans, Neanderthals may have been interbreeding with some of the ancestors of modern Eurasians as recently as 37,000 years ago. And another recent study found that Asian and South American people possess an even greater percentage of Neanderthal genes.

"These are complexities in the out-of-Africa story that certainly I would not have anticipated two or three years ago," said Chris Stringer, a paleoanthropologist at the Natural History Museum in London and author of Lone Survivors: How We Came to Be the Only Humans on Earth.

In their original incarnation, Neanderthals were viewed as the primitive, backward cave dwellers of Eurasia, far less complex than the sophisticated Homo sapiens who used language and developed sophisticated art as they migrated out of Africa and conquered the world.

But new studies are making it much harder to draw a clean line between us and them.

"It's increasingly difficult to point to any one thing that Neanderthals did and Homo sapiens didn't do and vice versa," said John Shea, an archaeologist at Stony Brook University in New York.

"These Ice Age people, both Neanderthals and Homo sapiens, survived, thrived, and increased their numbers under conditions that would probably kill people nowadays, even ones that are equipped with modern survival technology."

The draft sequence of the Neanderthal genome, published in the journal Science in 2010, provided the first compelling genetic evidence that Neanderthals and H. sapiens had more in common than just an ancestor in Africa hundreds of thousands of years ago.

The researchers, under the direction of Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology, found that 2.5 percent of the genome of an average human living outside Africa today is made up of Neanderthal DNA. The average modern African has none.

This suggested that some interbreeding had taken place between the two kinds of human, probably in the Middle East, where the early modern humans migrating out of Africa would have encountered Neanderthals already living there.

The even larger percentage of Neanderthal DNA found in Asians and South Americans, announced in Science in August, could indicate additional interbreeding in Asia long ago, or could mean that the percentage of Neanderthal DNA in Europeans was diluted by later encounters.

Not everyone is convinced that interbreeding was responsible for similarities in the Neanderthal and H. sapiens genomes. "The similarities they're seeing may be ancient," Shea noted.

Another recent study, published in the journal Proceedings of the National Academy of Sciences in August, calculated that the shared DNA could have come from an earlier, common ancestor of Neanderthals and H. sapiens—no hanky-panky necessary.

A new study by Pääbo's team, published last week in PLOS Genetics, also considered the possibility that the presence of Neanderthal DNA in people living outside Africa today could be traced far back, to the common ancestor of both Neanderthals and modern humans in Africa.

Perhaps the early modern humans who left Africa 60,000 years ago were already genetically more similar to the Neanderthals—who had left hundreds of thousands of years before—than were the modern human populations that stayed behind in Africa. In that case, no interbreeding would have needed to occur to account for the trace of Neanderthal DNA in non-Africans today.

To test the two hypotheses, Pääbo's group analyzed the lengths of segments of Neanderthal DNA in modern Europeans to determine when Neanderthal genes may have mixed with those of modern humans. The date they came up with for the gene flow was 37,000 to 86,000 years ago, and most likely 47,000 to 65,000 years ago.

This date strongly suggests there was indeed interbreeding between "us and them," when H. sapiens was moving into the Middle East from Africa and would have encountered populations of Neanderthals already settled there.

"This [interbreeding] could have been a really powerful mechanism for humans to adapt as they moved into Eurasia," said Sriram Sankararaman, a statistical geneticist at Harvard Medical School and the lead author of the PLOS Genetics study.

Another group, publishing last year in Science, for example, determined that modern humans gained from Neanderthals a family of genes that helps the immune system fight off viruses. Breeding with the locals could have unwittingly given H. sapiens a survival advantage in a new land.

"[Neanderthals] are not just some extinct group of related hominids," Pääbo said. "They are partially ancestors to people who live today."

Take any two unrelated humans today, Pääbo noted, and they'll differ in millions of places in their genetic code. But the Neanderthal genome varies on average from that of H. sapiens in only about a hundred thousand positions. Pääbo and his colleagues are now trying to figure out the consequences of those differences.

Regardless of the similarities to our DNA, how "human" were Neanderthals in their sensibilities?

Last month a study led by the Gibraltar Museum and published in PLOS ONE documented a multitude of fossil remains of bird wings, particularly from big black raptors, at Neanderthal sites in southern Europe. The team suggested that Neanderthals could have been plucking feathers from the wings for personal use or even for ritual ornaments.

"We have other evidence for Neanderthals preferring mineral pigments that are dark, blackish color," Stony Brook's Shea said. "There may be something for them with the color black just as there seems to be something for us with the colour red."

Sophisticated art, however, still appears to remain in the realm of H. sapiens.

The ancestors of modern humans left behind images of animals and other objects in caves around the world, most famously at Lascaux cave and Chauvet Cave (pictures) in southern France. Paintings in the latter cave could be as ancient as 37,000 years old. (See a prehistoric time line.)

Images found in a cave called El Castillo on the Spanish coast were recently dated at more than 40,800 years old: a time before Neanderthals disappeared, raising the tantalizing possibility that they were indeed the artists. However, "it hasn't been demonstrated that Neanderthals produced any of that cave art," the Natural History Museum's Stringer said.

The simpler answer is that H. sapiens, who had also reached Europe by that time and are known to have produced later but similar art, were responsible.

Neanderthals, though, have proven advanced in other ways.

They used pigments and may have made jewellery; some made complex tools. "We know they buried their dead," Stringer said. In 2010, researchers from the Smithsonian Institution even found evidence that the Neanderthal diet included a diverse mixture of plants, and that they cooked some of the grains.

"Cooking something like oatmeal is not what we would have imagined," said John Hawks, paleoanthropologist at the University of Wisconsin-Madison. With no pots, Neanderthals may have cooked inside leaves, Hawks suggested. "That starts to sound like cuisine."

"Neanderthals have gone from being different from us to being like us," Hawks noted. "They're looking like [Homo sapiens] hunter-gatherers look."

But while modern humans continued to develop cultural complexity and spread across the globe, the Neanderthals vanished. Why remains a mystery.