When I was a teenager in Israel, I once hiked on Mount Carmel with a bunch of my buddies. We came to the site of a cave, the Tabun cave, that contained the skeleton of a woman that lived there about 120,000 years ago. But, she wasn’t human, by which I mean the Homo sapiens species. She was a Neanderthal (Homo neanderthalensis). Practically next door, there was another cave, where many other skeletons were found, only they were not Neanderthals, but rather an early version of Homo sapiens (aka archaic H. sapiens).

tabun
The Nahal Me’arot cliff, Mount Carmel, Israel, showing the prehistoric caves of el-Wad, Jamal and Tabun | by R Yeshurun | CC by SA 3.0

As unruly teenagers, we couldn’t resist making the obvious jokes about humans having sex with Neanderthals? Of course, we were scolded by our youth movement guide who told us, first of all, we were disrespectful, and second, we were stupid because by the time humans made Aliyah (i.e., migrated to Israel) from Africa, all the Neanderthals had migrated to Europe. There was no overlap.

It turns out we weren’t stupid (or at least not that stupid), we were just ahead of our time. A few months ago, a group of archaeologists writing in the journal Nature, described finding a human skull that dated back to 55,000 years ago in a cave by the Sea of Galilee—the same place where Jesus plied his trade 53,000 years later.

Not only did Neanderthals live in the Middle East at that time, but several caves in the vicinity of Mount Carmel were inhabited by them. They lived at the same time and in the same vicinity as ancient humans. So again, I ask the question: Did they have sex with each other?

We no longer do we have to resort to the fevered imagination of Israeli teenagers to get to the answer. Genome studies of Neanderthals and of both ancient and contemporary H. sapiens suggest that the two species interbred somewhere in the Middle East between 50,000 and 60,000 years ago.

 

Is there a Neanderthal lurking in your genes?

If you are of European or Asian descent then, in all likelihood, you are part Neanderthal. Although Neanderthal genes are only a small part of our genome to be sure (about 2-4%), it could actually be making an important contribution to who we are.

Bonobo photo: By Psych USD (CC BY-SA 3.0)
Bonobo | via Psych USD | CC BY-SA 3.0

Consider this: Only about 1-4% of our genome makes us modern humans. The rest of our genome is identical to lower primates. We are 96% identical to the chimpanzees and 99% to the bonobos. Look at what a huge difference this small percent has made, for better or for worse.

But wait, what we now know is, for some people, 2-4% of the 1-4% difference between us and lower primates is actually Neanderthal! And, that’s the contribution from only one closely related species of humans, the Neanderthals.

 

What about other human species?

Denisovans or Denisova hominins are another extinct species of human in the genus homo. In March 2010, scientists announced the discovery of a finger bone fragment from a juvenile female who lived about 41,000 years ago. It was found in the remote Denisova cave in the Altai mountains in Siberia, a cave that has also been inhabited by Neanderthals and modern humans.

So, again I ask: Was there interbreeding? How could there not be? About 17% of the Neanderthal genome from skeletons found there is Denisovan. Tests comparing the Denisova hominin genome with those of six modern humans showed that between 4% and 6% of the genome of Melanesians derives from a Denisovan population. This DNA was possibly introduced during the early migration to Melanesia.

Melanesians may not be the only modern-day descendants of Denisovans. Population geneticist David Reich of Harvard, in collaboration with Mark Stoneking of the Planck Institute team, found genetic evidence that Denisovan ancestry is shared by Melanesians, Australian aboriginals, and smaller scattered groups of people in Southeast Asia. Their genome is 5% Denisovan. The data places the interbreeding event in mainland Southeast Asia and suggests that Denisovans once ranged widely over eastern Asia.

These examples are only the tip of the iceberg. More discoveries of cousin hominins are sure to come because evidence is accruing that the family history of the human species doesn’t look like a tree, but rather like a bush, with as yet undiscovered stems and branches.

 

How Neanderthal and other hominin genes helped our species survive

This post would have ended here if that was all to the story. But as it happens, these slivers of “alien” DNA have an outsize effect on our biology. An article in Nature reviews some of those effects.

Take something as basic as our immune response. Everybody is familiar with adaptive immunity, in which, after exposure to pathogens, we develop antibodies and lymphocytes programmed to specifically attack them. But that takes time, a minimum of 7-10 days if the pathogen has never been encountered before. To be left defenseless during that period would result in certain death.

To the rescue comes an immune system, called innate immunity. How does it work? We have 10 variants of a peptide called TLR (Toll-like Receptor). This peptide does not recognize specific organisms, but it recognizes certain molecular patterns that don’t exist in humans. When such a molecular pattern binds to the TLR, it activates white cells to go on the attack against the organism, be it bacteria or virus, and annihilate it. And here is the surprise: Genomic analysis revealed that we have to give thanks to our Neanderthal relatives for making a major contribution toward development of this first line of defense.

Neanderthals even helped us with adaptive immunity. As macrophages engulf and digest dangerous invaders, they chew them up and spit out the broken down peptides of the pathogen’s proteins. On their membrane, these macrophages have proteins called HLA (Human Leukocyte Antigens) which perform the most basic thing the immune response does: recognize self from non-self. If they bind a pathogen’s broken down peptide and don’t recognize it as self, they set in motion synthesis of antibodies to that particular pathogen. So far, four families of HLA peptides, each containing about 1000 variants, have been identified. One of those families, present in 75% of Europeans, is Neanderthal!

What about non-immunological genetic contributions? As we lost our pigmentation coming out of Africa, we became exposed to the harmful effects of UV radiation. How could the new immigrants to the Middle East and Europe adapt quickly enough before being completely wiped out by the sun’s radiation? The welcoming local Neanderthals made sure that we’d survive the old fashion way: They made love to us, and in the process transferred a gene protective of UV-B radiation. They also saw us suffering from hitherto unfamiliar cold temperatures of Europe and gave us a series of genes involved in the inner workings of cells called keratinocytes, which make up most of the outer layer of human skin and produce hair.

 

And what about the Denisovan contributions?

Tibetans in the clouds | by darcym | CC BY-NC-ND
Tibetans in the clouds | by darcym | CC BY-NC-ND

Denisovan’s also made significant contributions to the human genome? Here’s a striking example. Tibetans adapted to living in high altitudes that would make you and me gasp for air. It turns out they have a variant of a gene, EPAS1, that allows them to function at such altitudes. The source of the gene? Their Denisovan ancestors.

So why don’t the Han Chinese have this gene variant? A tiny minority of them do have it, but because of natural selection, it largely disappeared in the majority of Han because, at lower elevations, it had no survival advantage.

 

Was it all fun and games?

As you read this post, you might think that it was written by a Neanderthal advocate. Far from it. There are a whole lot of Neanderthal genes that are not found in humans. There are long stretches of DNA where you don’t have a trace of Neanderthal genes. Why is that? Most likely, because these genes were actually deleterious and those unfortunate individuals who inherited them were “bred out” by natural selection. Case in point: the X chromosome is totally devoid of Neanderthal genes, most likely because they reduced fertility. The obvious consequence was rapid elimination from the gene pool.

 

Let us give thanks

So all you Europeans and Asians (myself included), take note. We probably wouldn’t exist today, at least not in our present form, if it were not for those open-minded Neanderthals who mated with our ancient Homo sapiens ancestors. The result of these interspecies liaisons was the transfer to our species of the genes that now protect us from unfamiliar pathogens, UV irradiation, and bitter cold. We owe them a debt of gratitude and, for sure, we should be proud of their contributions to our well-being.


Featured Photo Credit: Wikimedia Commons

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

42 COMMENTS

  1. If the contribution of Neanderthal is about 2 to 4 % in the today Homosapiens, could we analyze the reverse impact, what is the contribution of Sapiens in the today Neanderthal-Sapiens?

  2. I am no expert on the subject, but I really like this theme and I found very interesting article. I read some time ago that some researchers have hypothesized that art was an Neanderthal contribution. Do you know anything about it? What is your opinion? Greetings and congratulations on your article

  3. From the uneducated. Why not reverse the directions? Maybe the Indians of the Americans migrated west. I noticed most people say the directional movement of migration as a fact.

  4. I have nothing to do with science but as I understand this very interesting issue about our origin.. Then Homo Sapiens and Neanderthals were compatible genetically, thus only different races of same species. Like today when an European has a kid with an indigenous tzeltal person in Chiapas. Only different families living simultaneously, adapting to different altitudes, sun exposure, food but still compatible genetically. It doesn’t seem one of those families was really less human.

  5. Dov, Dov, Dov! Good Shabbas and a Happy Hanukah … BUT if Neanderthlia is genetically based, how is it that the majority of Republicans in the U.S. and of Likudniks in Eretz Yisrael have much more than a trace?

    • Aha! good point. These genetic numbers are averages. Some have a lot more, others have none.
      But before we insult the Neanderthals with association with Republicans or likudniks, let me dispel a misconception: they were not dumb at all. They made jewelery, which indicates a high degree of social organization and culture. They haven’t developed writing, and probably could only grunt because their vocal box was anatomically more ape-like. But they inhabited Europe when we were still on the trees in Africa, probably grunting like they did, and developing writing only tens of thousands of years after they became extinct.

  6. Its been a very informative to my today’s knowledge, i really wonder how some humans remained black and some went white. I guess someday all will turn white. The one which more fascinates me is, would we..!! be able to stop diseases transmitted hereditary-cally to our next generation by choosing the right partner (gene, wife/husband) .

    • The theory is that the melanin pigmentation of African black people provides protection from the intense UV radiation of the tropical sun. The new migrants out of Africa to the middle east and on to Europe faced a much reduced risk of the UV radiation, but needed more sunlight to activate their vitamin D, needed for bone nimeralization. Hence, there was a selective advantage to losing the pigmentation.

  7. Your question about the facial features of the people of the east (chinese, mongolian) is interesting. The Denisovans, who inhabited Siberia, Mongolia and Northern China of today, apparently are a branch that split off from the early Neanderthals. The polynesians have Denisovan genes in their genome. So do the Tibetans.On the other hand,the Han Chinese have little or no Denisovan genes in their genome. there is also genetic evidence that the polynesians, who started out as hill dwellers in Taiwan, have Denisovan genes in their genome. So what does all this tell us? That we cannot lump all “oriental people” together. There were many nomadic groups, interbreeding, and givng us today’s rich melange of ethnic groups. And evolution didn’t stop then. One can easily distinguish between today’s Hsn Chinese and Tibetans, Vietnamese, Meos of the hill country of Laos and northern Thailand, Koreans, and Japanese.

    • On the last sentence… “One can easily distinguish between today’s Hsn Chinese and Tibetans, Vietnamese, Meos of the hill country of Laos and northern Thailand, Koreans, and Japanese.”… We have a joke (in Portuguese) that goes: “If you want to distinguish a Chinese from a Japanese, ask them to say “laranja” (/laˈɾɐ̃ʒɐ/)… If it is spoken “lalanja”, than you have a Chinese, if you hear “raranja”, you spoted your Japanese”… It always fascinated me! All the best, and thanks for the article!

  8. I studied anthropology as a major but never worked in that field. I have tried to keep up with the latest findings and I must comment about the “southern Russia” phrase. My research from Proto-Celts to my Slavic roots who were the last of the migration from WESTERN MONGOLIA.
    As a prelude to the Neanderthal there are three items I that I wish to mention about this era.
    A few years ago a Chinese anthropologist claims that the origin of Hominids is China! No one has disputed his theory yet (and why do the Asians have a distinctive facial feature?).
    Another anthropologist claims that the tribes of the Mongolian area were Turkic-Germanic (Turk tribes that spoke either Germanic or Turkic dialects and vice-versa for German tribes. He then begs the question “Are we all German?” because the Celts, Goths and Visigoths (honorable mention for the Anglo and Saxons) were Germanic languages influenced by Latin and ‘rude’ Latin (with a bit of Nordic infection) that created the European languages.
    Would that be also true for the tribes that went east? Shall we call them Polynesian and include the American aborigine?

    I use myself as an example of Neanderthal heritage. I have a simian crest, long torso, pronounced incisors and long arms (36″) in contrast to relatively short legs (30″).

  9. Funny that IE and PIE should be raised with this topic. I became ‘aware’ of the strong and even obvious relationships between European and Asian language families a bit late my learning game (in my formative twenties – with, oddly enough, a sudden interest in medieval and ancient English history). It was what my older brother could casually tell me when I was something under 12 that many knew yet didnt know why, that the languages of Europeans were ‘all’ more or less closely related (he always blew me away with what he knew). The broad consensus (I believe) is that the second theory has always had more scholarly acceptance. Its not to say that the Anatolians didn’t make a significant contribution. Their influence on southern Europe is well known – in some circles anyway – and some days I cant seem to get enough about ancient and neolithic Anatolia alone to satisfy my appetite for it.

    With the recent advances in DNA testing (successfully extracting bone cell DNA from stone age skeletons has made all the difference) researchers have been able to lend credence to the view that the dispersal of paleolithic people from Western Siberia lent their DNA to Western and Northern Europeans and (surprise!) to Native Americans. Seems they went ‘everywhere’ and took their talents with them!

    It stands to reason the voice of that hot bed of speech (we call it ‘Southern Russia’ but it is so much more) has been heard the world over for as long as anyone can remember, and that’s just the IE side of things.

    Thanks! You guys have just set me off on a tangent again…but I dont want to wear anybody down. Ill just keep on reading.

    • Thank you Rene. I too find linguistics and what it tells us about ancient history endlessly fascinating.You are right about the Anatolian influence. In fact, Akkadian and Hittite show only tenuous relationship, if any, to PIE and PI. Akkadian and Sumerian were the llanguages of ancient Mesopotomia. The former is related to Semitic languages such as ancient Aramaic. As far as Sumerian, the language of the most ancient civilization -I don’t know its origin. It bears little resimblence to Akkadian, which slowly displaced it. To my untrained ear/eye, it resembles Hittite, which was spoken in Anatolia.

      • Sumerian is unclassified and Akkadian is Semitic, but Hittite is an Indo-European language. The Anatolian group to which it belongs, though, seems to have been the first to split off from the shared IE speech, so it stands to reason that it sounds the most distinctive. (The apparent second group to split off from IE, Tokharian, went into eastern Central Asia (including Xinjiang) and is now also completely extinct.)

  10. Highly informative and useful to know as to how the Europeans and middle East people lost their original black colour and as to why Tibetans don’t gasp like some of the Chinese men while ascending mountains. Genes made the difference as revealed in their colours, immune systems, and living habits. Now it fires up my imagination to differentiate Indians from one another on the basis of theirs colours, features and living habits. I am professor of English and willing to know from you the ancestry of IndoEuropeans.

    • You touched on a controversial issue. There are two competing theories. One claims that farmers living in Anatolia and migrated into Europe about 8000 years ago, bringing with them their language, PIE (Proto Indo-European), which then evolved into the many Indo-European languages of today. The other theory claims that PIE arose about 6000 years ago in herders living in the vast Pontic steppe north of the Black Sea, where Kazakhstan, Ukraine and Russia intersect. About 4000 years ago they migrated into central Europe and that’s when Indo-European evolved into the many language families of today. Two recent papers provide support, albeit not definitive, for the latter hypothesis. One paper in Nature, is based on analysis of ancient DNA from skeletons from that period
      (http://www.nature.com/nature/journal/v522/n7555/full/nature14317.html). the other paper is based on linguistic analysis and came to the same conclusion (http://news.sciencemag.org/archaeology/2015/02/mysterious-indo-european-homeland-may-have-been-steppes-ukraine-and-russia)
      I believe that the jury is still out, although I tend to give more credence to the latest papers I cited.

    • I’m not a doctor but something tells me that the capacity the Tibetans have was an adaptation rather than the presence of a gene. At 3,675 meters La Paz, the capital of Bolivia in South America is the highest city in the world. Do they also have the referred gene?

      • Great question, Marcio. In general, natural selection comes up with different solutions to the same problem, and high-altitude adaptation is one of them. Unlike the Tibetans, the Quechua of the Andes have a higher concentration of hemoglobin (called hematocrit) in the blood, and when they move to the lowlands their hematocrit drops. But they have another adaptation: their hemoglobin binds more oxygen than us lowlanders, and this doesn’t change even when they move to lower elevations.
        The highlanders of Ethiopia also adapted to high altitude by increase in their Hematocrit. But their hemoglobin does not bind more oxygen than normal.Both the Andes people and the Ethiopians have a higher level of the hormone that stimulated red cell production, called erythropietin (EPO).
        Finally, competitive long distance runners move to high elevations (like Colorado) to train there before an event, so that their hemoglobin concentration -and hence their oxygen binding capacity- increases. Also, professional bicycle athletes “dope” their blood with hormones, like EPO, that increase their red blood cell (and hemoglobin) production.

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