The genes of the ancestors

When I had my DNA tested two years ago, I found out I have 330 distinctly Neanderthal markers in my genes.  This, apparently, is well above average for people of western European descent, and may explain why I like to run around half-naked and prefer my steaks medium-rare.

In all seriousness, most people of European descent have Neanderthal ancestry; it's less common in people of African and Asian ancestry, and in the indigenous peoples of Australia and North America.  It makes sense, once you know where they lived.  The Neanderthals were a predominantly European species (or sub-species; the experts differ, and honestly, the definition of species is so mushy anyhow that it's probably splitting hairs to argue about it).  They seem to have split off from the main population of hominins in the region something like five hundred thousand years ago.  The first unambiguously Neanderthal bones are 430,000 years old, and they persisted until 40,000 years ago -- and we still don't know why they died out.

What's certain is that it wasn't a lack of sophistication and intelligence by comparison with contemporaneous Homo sapiens, whatever you might have gleaned from Jean Auel's The Clan of the Cave Bear.  The Neanderthals were plenty smart.  They had culture, made paintings on cave walls, and created jewelry.  To judge by the Divje Babe flute they made music.  They ceremonially anointed their dead, and appear to have had some concept of an afterlife.  They had the same version of the FOX-P2 gene we do, suggesting they had spoken language.  So despite my earlier quip, Neanderthals were far from the slow, sluggish, stupid "cave men" we often picture when we hear the name.

[Image licensed under the Creative Commons Werner Ustorf, Neanderthal man reconstruction, Natural History Museum, London, CC BY-SA 2.0]

As my own ancestry indicates, there was a good bit of crossbreeding between Neanderthals and "modern" humans.  (I put modern in quotes not only because it's self-congratulatory, but because all organisms on Earth have exactly the same time duration of their ancestral lineages; words like primitive and modern really "less changed since the common ancestor" and "more changed since the common ancestor," but those are clunky.  So I'll continue to use primitive and modern, although with the caveat that they're not value judgments.)

What's interesting, though, is that the genetic input of the Neanderthals was asymmetrical.  Of the Neanderthal markers we carry around, none are on the Y chromosome, indicating that something blocked any contribution of Y-chromosomal genes from our Neanderthal forebears.  It's possible that the answer is simple -- that most inter-species matings were between "modern" human men and Neanderthal women.  But now a new study from The American Journal of Human Genetics, by Fernando Mendez, G. David Poznik, and Carlos Bustamante (of Stanford University), and Sergi Castellano (of the Max Planck Institute for Evolutionary Anthropology) has suggested another reason the Neanderthal Y chromosome didn't survive; mutations that caused male hybrid fetuses to spontaneously miscarry.

The authors write:

Sequencing the genomes of extinct hominids has reshaped our understanding of modern human origins.  Here, we analyze ∼120 kb of exome-captured Y-chromosome DNA from a Neandertal individual from El Sidrón, Spain.  We investigate its divergence from orthologous chimpanzee and modern human sequences and find strong support for a model that places the Neandertal lineage as an outgroup to modern human Y chromosomes—including A00, the highly divergent basal haplogroup.  We estimate that the time to the most recent common ancestor (TMRCA) of Neandertal and modern human Y chromosomes is ∼588 thousand years ago (kya)...  This is ∼2.1 times longer than the TMRCA of A00 and other extant modern human Y-chromosome lineages.  This estimate suggests that the Y-chromosome divergence mirrors the population divergence of Neandertals and modern human ancestors, and it refutes alternative scenarios of a relatively recent or super-archaic origin of Neandertal Y chromosomes.  The fact that the Neandertal Y we describe has never been observed in modern humans suggests that the lineage is most likely extinct.  We identify protein-coding differences between Neandertal and modern human Y chromosomes, including potentially damaging changes to PCDH11Y, TMSB4Y, USP9Y, and KDM5D.  Three of these changes are missense mutations in genes that produce male-specific minor histocompatibility (H-Y) antigens. Antigens derived from KDM5D, for example, are thought to elicit a maternal immune response during gestation.  It is possible that incompatibilities at one or more of these genes played a role in the reproductive isolation of the two groups.

Which is an interesting hypothesis.  It's possible, of course, that there was more than one thing going on, here; there may also have been a skewed distribution of genders in inter-species matings as well as a higher death rate in male children of male Neanderthals and female "modern" humans.   In fact, genetics and culture can sometimes create a feedback loop; the taboo in traditional Basque society against Basque women marrying non-Basque men is thought in part to have come from the high frequency amongst the Basques of the Rh negative blood group allele, resulting in children of Basque women (likely to be Rh negative) and non-Basque men (likely to be Rh positive) having a higher probability of dying of Rh incompatibility syndrome.

So sometimes cultural norms and genetics can intertwine in curious ways.

In any case, that's today's science story, tying together anthropology, genetics, and evolutionary biology, all particular fascinations of mine.  And the fact that it could well be talking about some of my own ancestry adds a nice twist.  Hopefully my forebears will forgive me for my jab about running around naked.  Maybe the most Neanderthal thing about me is that I play the flute.  Kind of turns the "cave man" trope upside down, doesn't it?

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Rehabilitating our cousins

The Neanderthals have gotten an undeservedly bad reputation.

"Neanderthal" has become an insult for someone perceived as dumb, crude, vulgar, lacking in any sort of refinement.  This perception wasn't helped any by Jean Auel's Clan of the Cave Bear and its sequels, where the "Clan" (the Neanderthals) are primitive, ugly, brutal people (personified by the violent and cruel Broud), contrasted to the beautiful, heroic, sophisticated Cro Magnons (such as virile, handsome, blue-eyed Jondalar, who is portrayed basically as a prehistoric Liam Hemsworth, only sexier).  The truth is way more complex than that; they certainly weren't unintelligent, and in fact, the most recent Neanderthals had an average brain size larger than a modern human's.  (I'm aware that brain size doesn't necessarily correlate with higher intelligence, but the depiction of them as tiny-brained primitives is almost certainly false.)

They had culture; the Mousterian tool complex, with its beautifully fluted stone arrowhead points, was Neanderthal in origin.  They were builders, weavers, jewelry-makers, and knew the use of medicinal plants.  There's evidence that they made music -- the Divje Babe flute, from 43,000 years ago, was made by Neanderthals from a bear femur, was probably made by Neanderthals.  The structure of the Neanderthal hyoid bone, and the presence of the FoxP2 gene, strongly suggests that they had the capacity for language, although cognitive scientist Philip Lieberman suggests that their mouth morphology would have made it difficult or impossible to articulate nasal sounds and the phonemes /a/, /i/, /u/, /ɔ/, /g/, and /k/, so any language they had probably wasn't as rich phonetically as ours are.  (Although that, too, is an overgeneralization; as I pointed out in a post only a month ago, the phonemic inventory of modern languages varies all over the place, with some only having a dozen or so distinct sounds.)

Another thing that people tend to get wrong is that the Neanderthals were displaced by modern Homo sapiens, and eventually driven to extinction, because we were smarter, faster, and more sophisticated.  Which is not only false, it carries that hint of self-congratulation that should be an immediate tipoff that there's more to it.  It's undeniable that our Neanderthal cousins did diminish and eventually disappear something on the order of forty thousand years ago, but what caused it is uncertain at best.  Other hypotheses regarding why they declined are climatic shifts, disease, and loss of food sources... and, most interestingly, that they interbred with, and were eventually subsumed by, modern humans.  Genetic analysis shows that a great many of us -- including most people of European ancestry -- contain genetic markers indicating Neanderthal ancestry.  Current estimates are that western Europeans have the highest percentage of Neanderthal DNA (at around four percent), while some groups, most notably sub-Saharan Africans, have almost none.

My own DNA apparently has 284 distinct Neanderthal markers, putting me in the sixtieth percentile.  So at least I'm above average in something.

[Image licensed under the Creative Commons Neanderthal-Museum, Mettmann, Homo sapiens neanderthalensis-Mr. N, CC BY-SA 4.0]

What brings this up is some new research indicating that the overlap between Neanderthals and anatomically modern humans may have lasted longer than we thought, and completely upends the picture of hordes of highly-advanced humans (led, of course, by Liam Hemsworth) sweeping over and destroying the primitive knuckle-dragging Neanderthal cave-dwellers.  Archaeologists working in the cave complex Grotte Mandrin, in the Rhône Valley of France, came upon a child's tooth and some stone tools (both of a distinctly modern sort), that date from 54,000 years ago -- a good twelve thousand years earlier than previous estimates.

"It wasn't an overnight takeover by modern humans," said Chris Stringer, of the Natural History Museum of London, who co-authored the paper.  "Sometimes Neanderthals had the advantage, sometimes modern humans had the advantage, so it was more finely balanced...  We have this ebb and flow.  The modern humans appear briefly, then there's a gap where maybe the climate just finished them off and then the Neanderthals come back again..  [W]e don't know the full story yet.  But with more data and with more DNA, more discoveries, we will get closer to the truth about what really happened at the end of the Neanderthal era."

Human history (and prehistory) are a lot more complex than you'd think on first glance, and it bears keeping in mind that usually when we build up a picture of something that happened in the past, we're working on (very) incomplete data filled in with guesses and surmises.  If a time machine is ever invented, and we can go back and look for ourselves, I think we'd be astonished at how much we missed -- or got flat wrong.

It reminds me of the famous quote by H. L. Mencken -- "For every problem, there is an answer that is clear, simple... and wrong."

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People made fun of Donald Rumsfeld for his statement that there are "known unknowns" -- things we know we don't know -- but a far larger number of "unknown unknowns," which are all the things we aren't even aware that we don't know.

While he certainly could have phrased it a little more clearly, and understand that I'm not in any way defending Donald Rumsfeld's other actions and statements, he certainly was right in this case.  It's profoundly humbling to find out how much we don't know, even about subjects about which we consider ourselves experts.  One of the most important things we need to do is to keep in mind not only that we might have things wrong, and that additional evidence may completely overturn what we thought we knew -- and more, that there are some things so far out of our ken that we may not even know they exist.

These ideas -- the perimeter of human knowledge, and the importance of being able to learn, relearn, change directions, and accept new information -- are the topic of psychologist Adam Grant's book Think Again: The Power of Knowing What You Don't Know.  In it, he explores not only how we are all riding around with blinders on, but how to take steps toward removing them, starting with not surrounding yourself with an echo chamber of like-minded people who might not even recognize that they have things wrong.  We should hold our own beliefs up to the light of scrutiny.  As Grant puts it, we should approach issues like scientists looking for the truth, not like a campaigning politician trying to convince an audience.

It's a book that challenges us to move past our stance of "clearly I'm right about this" to the more reasoned approach of "let me see if the evidence supports this."  In this era of media spin, fake news, and propaganda, it's a critical message -- and Think Again should be on everyone's to-read list.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Back to Africa

I was kind of tickled, when I got my "23 & Me" results back a couple of years ago, to find out that I had 284 identified Neanderthal markers, identifying me as having more Neanderthal ancestry than 60% of the samples tested.

The reason I was happy about this is not because it gave me an explanation for why I like my steaks rare and have a general aversion to wearing clothes.  It was more because I find the Neanderthals a fascinating bunch.  Far from the low-intelligence cave trolls a lot of us picture them as -- witness the use of their name as an insult -- by the end they actually had larger brains than your average modern Homo sapiens.  They had culture; they anointed and buried their dead, seem to have had music (if the archaeologists are correct about the origin of the Divje Babe flute), and might even have had language -- they had the same variant of the FOX-P2 gene that we do, which is instrumental to our ability to understand and produce spoken language.

[Image licensed under the Creative Commons Clemens Vasters, Neanderthal in a business suit, CC BY 2.0]

It also wasn't terribly surprising in my own case, as Europeans generally have more Neanderthal ancestry than any other group, and my test results showed me to be -- also unsurprising, given what I know of my family tree -- nearly 100% of European origin, mainly French, Scottish, Dutch, German, and English.  The Neanderthals themselves are named after the Neander Valley of Germany, where archaeologists found the first fossils of the species (or subspecies, depending on who you believe).  So once it was determined that they had interbred with early modern Homo sapiens, their geographical distribution led to a (correct) surmise that Europeans would have more Neanderthal ancestry than other ethnic groups, for the same reason that southeast Asians and Native Australians have more Denisovan ancestry than the rest of us.

That's why a paper in Cell two weeks ago came as such a shock.  In it, a team led by Lu Chen of Princeton University found that a number of African ethnic groups, especially those in northern and western Africa, have a lot more Neanderthal ancestry than anyone realized.

Because it's still not as much as the Europeans have, and the African Neanderthal genes identified are variants usually found in Europe, the guess is that some of the European Homo sapiens/Neanderthal hybrids made their way across (or around) the Mediterranean in a "back-to-Africa" migration, injecting Neanderthal genes into groups that previously had little to no Neanderthal ancestry.

It also means that geneticists may be underestimating the number of Neanderthal markers in the rest of us.  Because those estimates were made using comparison between sample DNA and that of people thought to have no Neanderthal ancestry at all -- such as the Yoruba of Nigeria -- if those African groups did have ancestry that was the result of a back-to-Africa migration by European hybrids, then that revises the baseline upward.  The former estimates of 1.7-1.8% Neanderthal DNA for your average person of European descent might be on the low side.

"Our work highlights how humans and Neanderthals interacted for hundreds of thousands of years, with populations dispersing out of and back into Africa," said study co-author Joshua Akey in an interview with Science News.  "Remnants of Neanderthal DNA survive in every modern human population studied to date."

I find it fascinating how DNA is now being used to track relationships and migratory patterns not only of other animal species, but of humans.  And it's gotten pretty accurate.  It picked up my Ashkenazic ancestry, identifying it at 6% -- just about right based on my one great-great-grandfather, Solomon Meyer-Lévy of Dauendorf, Alsace, who emigrated from his birthplace and joined a small community of French-speaking Jews in Donaldsonville, Louisiana in around 1850.  The other interesting result in my own DNA that made sense was a smattering of Italian ancestry, undoubtedly because my father's paternal line ancestor, Jacques-Esprit Ariey-Bonnet, was born in a little town in the French Alps, quite close to the border of Italy.

So the amount we can learn about our own past from our genes is staggering, and I'm sure there are other surprises in store for us.  It informs us not only of our physical makeup but our history, a millions-of-years-long trail leading back to our most distant hominid ancestors on the savannas of Kenya and Tanzania.

Although it still doesn't explain the rare steaks and nudity thing.

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This week's book recommendation is a fascinating journey into a topic we've visited often here at Skeptophilia -- the question of how science advances.

In The Second Kind of Impossible, Princeton University physicist Paul Steinhardt describes his thirty-year-long quest to prove the existence of a radically new form of matter, something he terms quasicrystals, materials that are ordered but non-periodic.  Faced for years with scoffing from other scientists, who pronounced the whole concept impossible, Steinhardt persisted, ultimately demonstrating that an aluminum-manganese alloy he and fellow physicists Luca Bindi created had all the characteristics of a quasicrystal -- a discovery that earned them the 2018 Aspen Institute Prize for Collaboration and Scientific Research.

Steinhardt's book, however, doesn't bog down in technical details.  It reads like a detective story -- a scientist's search for evidence to support his explanation for a piece of how the world works.  It's a fascinating tale of persistence, creativity, and ingenuity -- one that ultimately led to a reshaping of our understanding of matter itself.

[Note: if you purchase this book from the image/link below, part of the proceeds goes to support Skeptophilia!]

Neanderthal family reunion

Last year, I did a 23 and Me DNA test.

Besides the not-particularly-earthshattering conclusion that I'm mostly French, Scottish, German, and Dutch, I was amused to find that the test showed I have 284 Neanderthal markers.  This puts me in the 60th percentile as compared to the population overall, which probably explains why I like my steaks rare and run around half naked when the weather is warm.

What's fascinating is that some research released last week, a paper in Cell by David Enard of the University of Arizona and Dmitri A. Petrov of Stanford University called, "Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans," has shown that some of these genes didn't get passed along the usual way, but by a process called transduction -- when viruses transmitted from one host to another carry novel genes with them.

The authors write:

After their divergence 500,000 to 800,000 years ago, modern humans and Neanderthals interbred at least twice: the first time ∼100,000 years ago and the second ∼50,000 years ago.  The first interbreeding episode left introgressed segments (IS) of modern human ancestry within Neanderthal genomes, as revealed by the analysis of ancient DNA from a single Altai Neanderthal individual sequenced by Prüfer et al. (2014).  This first interbreeding event appears not to have left any detectable segments of Neanderthal ancestry in extant modern human genomes.  In contrast, the second interbreeding episode left detectable IS of Neanderthal ancestry within the genomes of non-African modern humans. 

Recent advances in the detection of introgression have led to the discovery that the majority of genomic segments initially introgressed from Neanderthals to modern humans were rapidly removed by purifying selection.  Harris and Nielsen (2016) estimated that the proportion of Neanderthal ancestry in modern human genomes rapidly fell from ∼10% to the current levels of 2%–3% in modern Asians and Europeans.
This history of interbreeding and purifying selection against IS raises several important questions. First, among the introgressed sequences that were ultimately retained, can we detect which sequences persisted by chance because they were not as deleterious or not deleterious at all to the recipient species, and which persisted not despite natural selection but because of it—that is, which IS increased in frequency due to positive selection?  If any of the introgressed sequences were indeed driven into the recipient species due to positive selection, can we determine which pressures in the environment drove this adaptation? 

Recently we found that proteins that interact with viruses (virus-interacting proteins [VIPs]) evolve under both stronger purifying selection and tend to adapt at much higher rates compared to similar proteins that do not interact with viruses.  We estimated that interactions with viruses accounted for ∼30% of protein adaptation in the human lineage.   Because viruses appear to have driven so much adaptation in the human lineage, and because it is plausible that when Neanderthals and modern humans interbred they also exchanged viruses either directly by contact or via their shared environment, we hypothesized that some introgressed sequences might have provided a measure of protection against the exchanged viruses and were driven into the recipient species by positive directional selection.  Consistent with this model, several cases of likely adaptive introgression from Neanderthals to modern humans involve immune genes that are specialized to deal with pathogens including viruses.

Which is amazingly cool.  Viruses are parasites, and as such usually wreak havoc with our systems, but here we have viruses acting as carriers not only for genes that generate diversity, but that protect our cells from the damage viruses can cause.

Great-great grandpa Ugg [Image licensed under the Creative Commons Stefan Scheer, Neandertaler reconst, CC BY-SA 3.0]

"It's not a stretch to imagine that when modern humans met up with Neanderthals, they infected each other with pathogens that came from their respective environments," lead author David Enard said.  "By interbreeding with each other, they also passed along genetic adaptations to cope with some of those pathogens."

"Many Neanderthal sequences have been lost in modern humans, but some stayed and appear to have quickly increased to high frequencies at the time of contact, suggestive of their selective benefits at that time," Petrov said.  "Our research aims to understand why that was the case.  We believe that resistance to specific RNA viruses provided by these Neanderthal sequences was likely a big part of the reason for their selective benefits."

"One of the things that population geneticists have wondered about is why we have maintained these stretches of Neanderthal DNA in our own genomes," Enard added.  "This study suggests that one of the roles of those genes was to provide us with some protection against pathogens as we moved into new environments."

So having Neanderthal DNA isn't something to be ashamed of.  All of this highlights how incredibly cool the evolutionary model is, and the depth of its explanatory power.  Now, y'all'll have to excuse me.  I'm going to go get a snack.  I wonder if I have any roast mammoth left in the fridge?  Probably not.  I guess grilled cheese will have to do.

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This week's Skeptophilia book recommendation is from the brilliant essayist and polymath John McPhee, frequent contributor to the New Yorker.  I swear, he can make anything interesting; he did a book on citrus growers in Florida that's absolutely fascinating.  But even by his standards, his book The Control of Nature is fantastic.  He looks at times that humans have attempted to hold back the forces of nature -- the attempts to keep the Mississippi River from changing its path to what is now the Atchafalaya River, efforts in California to stop wildfires and mudslides, and a crazy -- and ultimately successful -- plan to save a harbor in Iceland from a volcanic eruption using ice-cold seawater to freeze the lava.

Anyone who has interest in the natural world should read this book -- but it's not just about the events themselves, it's about the people who participated in them.  McPhee is phenomenal at presenting the human side of his investigations, and their stories will stick with you a long time after you close the last page.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]