Kyle Munkittrick of the "Science Not Fiction" blog argues, "Yes, we should clone Neanderthals."
A full response to this clearly deserves more thought than I can give right now. I'm going to keep pointing to arguments about the cloning issue, as I have done in the past with respect to human cloning.
I'm completely in favor of cloning Neandertal tissue cultures. I really think we can learn a lot about our biology by understanding that part of our evolutionary history at a cellular level, and that knowledge may well help people.
But making a whole person is different. Not only in an ethical sense but also a practical one, as our ability to understand the brain and immune system in living people isn't mature enough to make meaningful predictions about the small genetic differences between Neandertals and living people.
Of course today this is all just idle talk. Someone who's talking about other extinct species, I don't take very seriously. We're talking about an ancient population of humans here. Not like quaggas; more like Tasmanians -- a group of people whose culture hasn't survived, and yet still has many living descendants. This shouldn't be a conversation about cloning, it should be about the logical consequence: adoption. Who will step up to adopt a Neandertal child, and why aren't they helping living children instead?
Blaine Bettinger (the Genetic Genealogist) writes that some commercial test offerings are trying to sort out a way to tell you how Neandertal you are:
Once [the Max Planck] study came out, I knew it was only a matter of time before companies began offering tests that examined the percent of Neanderthal contribution to a test-taker’s genome.
This is one of the stickiest places to be a blogger. Bettinger links to a testing company's information on its product (including promotion of "Neandertal themed art" for the customer, sold at their Las Vegas gallery). Others have linked to Bettinger, drawing more attention.
I think that as a scientist, more promotion is the last thing I should be giving this company. So I won't be naming or linking to their advertising.
Ironically, the promotional material does not make any false statements of fact. The material makes it perfectly clear that the product does not test any gene variants that scientific research has shown may have come from Neandertals. Instead, the product reports on gene variants that we don't know about from Neandertals.
You may wonder how a company can market such a product as a "Neanderthal Index". Since "Neanderthal Index" is not a scientific concept, a company can claim whatever it wants.
So what is it? According to the material, the Neanderthal Index is computed from (a very few) STR alleles shared with "archaic" populations. Those "archaic" populations aren't Neandertals, they're Basques, Turks, Syrians, and other living people. Anthropologists do not call these people "archaic", so this is not a scientific concept either. Nobody has demonstrated that the listed populations are more or less Neandertal-like than any other living people. Most of the differences between these living populations emerged during the last 10,000 years.
You'd do better putting calipers on your skull and measuring your cephalic index. At least that would tell you whether some real phenotype is Neandertal-like.
I don't imagine that customers beating down the doors for this product. I think it exists as a way of bringing attention -- Neandertals are in the headlines. That's a big reason to not give them any attention. The test has nothing whatsoever to do with Neandertals as we scientifically understand them.
Can you tell that I'm disgusted by this?
Here in my lab, we're in a very good position to say that no test today can accurately report on your individual proportion of Neandertal ancestry. Until we have characterized a broader set of gene trees than we have so far, we are really not able to give any answer about how similar any person's genome is to Neandertals. We can't say yet how heterogeneous the human population is today in its ancestry from different parts of the world during the Late Pleistocene. For the past thirty years most working geneticists completely ignored the possibility of such heterogeneity, we are only just beginning to investigate it seriously.
This kind of thing may not be why the FDA is looking to regulate personal genomics. Neandertal ancestry is not directly relevant to health. But if customers buy tests like this thinking that they are learning about Uncle Thag, just how much misinformation will they accept from other tests that purport to tell them something more important?
This isn't normally the kind of story -- oh, who am I kidding? I love to snark on these kinds of stories!
"Popeye-like arms". Hmmmm....
Neandertals had a low brachial index -- that is, with a short forearm were relative to the humerus. Popeye, well, you can see that he has the brachial index of a giant ground sloth. Neandertals were not built like Popeye.
The article itself reports the ideas of a group of Russian scientists, who think that hormonal changes may explain the Neandertal pattern of muscle development and cortical bone strength.
Remains of an early Neanderthal with a super strong arm suggest that Neanderthal fellows were heavily pumped up on male hormones, possessing a hormonal status unlike anything that exists in humans today, according to a recent paper.
The mixture [of big muscles and highly mineralized bones] is puzzling, because "Neanderthals demonstrate a markedly androgenic constitution," meaning they seemed to have a lot of steroids, yet these same hormones can cause reduced mineralization.
As a result, the researchers say "Neanderthals were characterized not only by peculiar biomechanical adaptations, but also by a specific hormonal condition which has no close parallels among modern human hormonal conditions either normal or pathological."
There's no mechanism being proposed here, the androgen system has effects all over the body. This is not a testable hypothesis, it's really just a speculation.
Or is it? The cool thing about having a Neandertal genome is that in principle we can look for differences in systems like the androgen receptor pathway. Looking for coding changes in androgen-associated genes is really just a browser window away.
So I did some checking.
Now, let me put some caveats here. This is good blog material, but the Neandertal genome sequencing has not reached a point where we can be at all certain about mutations. There are many gaps with no coverage at all in any Neandertal individuals. Most of the sequence of human coding regions is covered by at least one read, and a good fraction of sites have multiple Neandertal reads. As I've been looking through sequence, I tend to think a site may be interesting if it has a change in the Neandertal relative to the human sequence, and if it's not near the end of a read. If the same change is present in multiple Neandertal reads, that makes it a good candidate for a genuine change in Neandertals relative to the human sequence. A large fraction of those Neandertal-specific changes actually aren't Neandertal at all. They're shared with chimpanzees and represent new human-specific changes. Many of those are SNPs in humans where the genome draft has the derived version; there are also sites where the Neandertal shares a derived SNP allele with some other humans. Then there are ones not in chimpanzees or humans, which might be Neandertal-specific alleles or substitutions.
Looking at the androgen receptor gene and the 5-alpha-reductase gene, both central to the androgen pathway, there aren't any interesting-looking sites in the Neandertal sequencing reads. I don't think the data refute the hypothesis that the Neandertals were like humans for these genes. That's just a little bit of looking, of course, and that particular fishing expedition wasn't likely to turn up anything new. But that's the point! We shouldn't just go off speculating about fundamental changes in hormonal biology in Neandertals anymore. We can look.
That is just the beginning of answering a question like this. To test the hypothesis, we'd want to check many other genes that lie between the androgen receptor and its final effects on gene transcription. And of course, coding changes aren't the whole story of evolution in Neandertals. Promoter and enhancer changes, or even alternative splicing changes, may be more important than coding changes, especially for a system so broadly represented in different tissues. They're harder to look for by just firing up the genome browser.
But even these kinds of changes are potentially testable. It's not quite as fast as an interview with a reporter, but it doesn't take days to look.
Back in 2005, I reviewed the first description of fossil chimpanzee teeth, from the Middle Pleistocene of the Kapthurin Formation, Kenya, dating to around 500,000 years ago. At the time, I noted that no chimpanzees have lived in the area in historic times, and that mtDNA evidence then suggested that East African chimpanzees (Pan troglodytes schweinfurthii) may have been recently derived from Central Africa. Together, those observations raised a mystery -- if today's chimps had no ancestors anywhere near Kenya 500,000 years ago, to what group did these fossil chimpanzee teeth belong? I suggested an answer: a cryptic population of chimpanzees partially or completely replaced by the dispersal of Eastern chimpanzees. In other words, Neanderchimps.
Well, now that we know for sure that Neandertals are human, too... it's a good time to revisit the Neanderchimps. What can we say today about the population structure of chimpanzees in the past, and is it still possible that these chimpanzee fossil teeth are out of kilter with the population genetics of today's chimpanzees?
A few weeks ago, we had Jody Hey visiting here on campus, and he gave a talk about his recent work on chimpanzee population genetics. Together with Rasmus Nielsen and others, Hey has been developing Bayesian methods for estimating the times of divergence, migration rates, and effective population sizes of species.
The basic idea is that present-day samples of a species like chimpanzees reflect a branching process from an ancestral population. Each branch may exchange migrants with other branches, each branch has an effective population size, and each may begin with some kind of population bottleneck. That makes for a very complicated model -- for example, with only two populations, there are six parameters, not counting bottlenecks. With each additional population, the number of parameters is compounded by additional effective size, time of splitting, and migration rate to and from all other populations. The number of parameters increases faster than a factorial of the number of populations.
Hey began this work several years ago, initially limited to the two-population case. Together with Yong-Jin Won, he showed that West African chimpanzees (P. troglodytes verus) have a substantially smaller effective size than central African chimpanzees (P. troglodytes troglodytes). These two subspecies appeared to have diverged within the last 300,000-400,000 years. And while there was little evidence for gene flow from central into west African chimpanzees, there was clear evidence for gene flow the other direction, from west into central Africa.
In a series of two-way analyses, Won and Hey showed that bonobos diverged from chimpanzees approximately 400,000-800,000 years ago, that there was no substantial evidence of gene flow into or out of bonobos after their speciation, and that the efective size of bonobos was around the same as that of west African chimpanzees, a bit under 10,000 effective individuals.
Now, in 2010, Hey has extended both the data and method to encompass more than a single divergence between two populations. In the case of Pan, Hey has included three extant subspecies of common chimpanzees (P. t. troglodytes, P. t. verus, and P. t. schweinfurthii), together with bonobos (P. paniscus). Among those, in a bifurcating model of population divergence, there are three speciation times, ten effective sizes, and lots of asymmetrical migration rates, all scaled in one way or another to mutation rate. It takes a lot of data to estimate these parameters simultaneously. The study uses 73 loci from an average of 78 individuals split among the populations, which is apparently not quite enough data to get good parameter estimates for the migration rates, as the probability surfaces for these are shallow and relatively unresolved with a few exceptions.
The parameters describing divergence times and effective sizes under the model have tighter posterior probability distributions, so that they are reasonably well estimated using these data. Here are the highlights:
1. Bonobos split from chimpanzees around 930,000 years ago (680,000-1.54 million).
2. The effective sizes of most populations were small (around 10,000 or less). The Pan ancestral population was moderately larger (around 17,000 effective individuals).
3. Only central African chimpanzees were substantially larger in effective size, upward of 25,000-30,000 effective individuals during the last 460,000 years.
4. All common chimpanzees (Pan troglodytes) descend from an ancestral population that existed 460,000 years ago (350,000-650,000).
5. East African chimpanzees split very recently, only around 93,000 years ago (41,000-157,000) from central African chimpanzees.
All these estimates result from a fairly restrictive model. Each population is described by two parameters, their interactions by an additional two parameters per population pair. The ideas of pulses of population mixture or founder effects are simply not possible in the model. I don't see this as a weakness -- I'd much rather begin with even simpler models. But it does mean that we cannot generalize the results past the model. In particular, we shouldn't compare these times and migration rates directly with those obtained under the model that Green and colleagues (2010) applied to the Neandertal genome.
But after those words of caution, what can we make of this proposed population history for chimpanzees? Here are some possible conclusions relevant to human evolution:
1. Eastern and central chimpanzee subspecies share a more recent history than would have been true of humans and Neandertal populations at the time the latter existed. Western chimpanzees are more distant from other chimps than the Neandertals and humans were from each other.
2. For that matter, population differences between MSA humans within Africa may have been nearly as great as those between eastern and central African chimpanzee subspecies.
3. Bonobos and chimpanzees split roughly a million years ago with little if any subsequent interbreeding. At least in the west (Africa, Europe and West Asia), Pleistocene human populations did not experience this kind of allopatric speciation. At the moment, I enter that as an assertion, which I'll follow up later by some discussion of the pre-Neandertal problem.
4. The effective sizes estimated for ancient human populations are not especially low.
5. Range expansions and partial or complete replacements were part of the population history of chimpanzees. They managed these dynamic events without handaxes, fire, projectile weapons, language, or any of the other proposed trappings of Pleistocene humans.
I want to follow up on a couple of these. First, effective size: You often hear people claiming that humans have much lower genetic diversity than chimpanzees. It is true only in a limited sense. Bonobos, west African and east African chimpanzees are populations with lower genetic variation than humans. The estimate for the effective size of the common chimpanzee ancestral population, 7100, is substantially lower than estimated for the human ancestral population during the same time period, a period stretching from roughly a million to 460,000 years ago. The common ancestral population of chimpanzees and bonobos is inferred to have had an effective size close to that of ancestral humans at the same time, around 17,000 effective individuals prior to a million years ago.
One may object that chimpanzees cover a much smaller area than Pleistocene humans, so we should expect their effective size to be much lower. But genetic variation can be related to population size only by assuming a population model, and Hey's analysis gives us a model quite starkly different from the usual. That doesn't mean it's correct, or that it is a better estimator of the census size of the ancient populations. But it reminds us that comparing the genetic variation of humans and chimpanzees is too simplistic; that the gene trees within each populations are very sensitive to the relative contributions of different parts of each species' range during the last 500,000 years. In chimpanzees, the high genetic variation mostly can be attributed to the central African subspecies; in humans, the extant genetic variation can mostly be attributed to Africa.
Let's ponder chimpanzee range expansions for a moment longer. We know that in the early Middle Pleistocene, chimpanzee-like apes lived in western Kenya. The only chimpanzees who live anywhere near that area today seem to have been much more strongly connected to chimpanzees in western Congo prior to 93,000 years ago, and that central African population still has much more variation than the eastern ones. That suggests a recent range expansion, Late Pleistocene in age, into East Africa.
We don't know that the earlier chimpanzees became extinct. They may have contributed genes into later P. schweinfurthii, just as Neandertals did into living humans. We can tell stories about climate change and the former East African chimpanzees, just as people have done about human origins, megadroughts and volcanoes. But one thing is clear about the chimpanzees: there was no modern chimpanzee revolution. The other chimpanzee subspecies, P. t. verus, is still here.
UPDATE (2010-05-20): "More on chimpanzee population structure" discusses a subsequent paper on the same topic.
Gagneux P, Gonder MK, Goldberg TL, Morin PA. 2001. Gene flow in wild chimpanzee populations: what genetic data tell us about chimpanzee movement over time and space. Phil Trans R Soc Lond B 356:889-897.
Goldberg TL, Ruvolo M. 1997. Molecular phylogenetics and historical biogeography of east African chimpanzees. Biol J Linn Soc 61:301-324.
Hey J. 2010. The divergence of chimpanzee species and subspecies as revealed in multipopulation isolation-with-migration analyses. Mol Biol Evol 27:921-933. doi:10.1093/molbev/msp298
McBrearty S, Jablonski NG. 2005. First fossil chimpanzee. Nature 437:105-108. doi:10.1038/nature04008
Won Y-J. Hey J. 2005. Divergence population genetics of chimpanzees. Mol Biol Evol 22:297-307. doi:10.1093/molbev/msi017
Regarding that cool new app from Apple/Smithsonian... I know it's really all just for fun, but seeing that there is only one Neandertal face for everyone to use, I began to wonder about adaptations they may have gone through in their 400,000 year reign. Seems to me that from France to China to the Levant that skin shades and certain facial features would arise (probably not the right word there) and that to keep the app really interesting that they should have a couple different Neandertal faces to choose from. Otherwise everyone will start to look too much alike.
Please know I know you have nothing to do with the app... just was curious about your thoughts on Neandertal adaptations and if what I'm griping (lightheartedly) about is reasonable?
I agree completely. It is characteristic for artist reconstructors to use skin tones and hair shades that reflect present-day people -- so the Near Eastern Neandertals are tanner and black-haired; the European ones light-haired and pale.
But that assumes a lot about the nature of the present variation. Now that we know that the genes with the largest effects on pigmentation are in fact very recently selected, there's really no reason to think that we fit our environments very well now (or in recent pre-industrial history). We might be stopped in the middle of going to even more extreme differences; or we might have gone much farther because of the availability of more adaptive variation to work with.
The variation in a long-adapted population like Neandertals might well be more than ours. Or less -- because they were a much smaller population with fewer chances at adaptive changes. It's really hard to predict .
If you want to give yourself a caveman (or cavewoman) makeover, well, now there's an app for that:
The MEanderthal app (a combination of "me" and "Neanderthal") just released by the Smithsonian National Museum of Natural History for the iPhone or Android, is grounded in science. It relies on what is known about the appearance of our closest extinct relatives, the Neanderthals, to transform your face into the face of an early human.
The art is based on John Gurche's reconstructions, so I guess you'll be Gurchelating yourself. Gurchetizing?