Neandertals

I have an excellent e-mail question about last week’s Neandertal mtDNA paper, which has provoked a lot of commentary.

Krause et al. (2007) list 15 Neandertal partial mtDNA sequences. Ten of these at that time presented relatively long portions, including the central Asian Okladnikov and Teshik Tash specimens, Mezmaiskaya, Feldhofer 1 and 2, Vindija 75 and 80, Scladina, Monte Lessini, and El Sidrón 1252. The same paper lists five additional specimens for which only a very short sequence had been recovered (just enough to diagnose as part of the Neandertal clade), including Vindija 77, El Sidrón 441, Engis 2, Rochers de Villeneuve, and La Chapelle-aux-Saints.

We do not know that every Neandertal belonged to the same mtDNA clade as those 15 sequences. Some of them may have looked different, possibly including the new clade otherwise present in later Upper Paleolithic and living people. But based on the 15 sequences we have, we can say that a large fraction of Neandertals must have carried the “Neandertal haplogroup.” Exactly how large a fraction depends on what we are willing to believe about contamination, preservation, and the randomness of our sample.

Now, let’s consider the question: Can we predict anything about Neandertal evolution and relationships based on this small, possibly unrepresentative sample of mtDNA?

The answer is that it doesn’t matter very much whether we have 5 sequences or 500. If 15 out of 15 specimens from different sites across Europe preserve a single mtDNA haplogroup, we can’t say it was universal, but we can say it was common. If 40 out of 50, or 400 out of 500 specimens had the same haplogroup, that would increase the precision, but not change the basic fact: Neandertals had at least one common haplogroup that is now so rare it has never been found in a sample of 100,000 or more people. We deserve some explanation.

The possible explanations are:

1. Random genetic drift
2. Accelerated genetic drift due to demographic turnover
3. Population extinction and replacement
4. Natural selection

Drift

Random genetic drift is fairly easy to refute, although it might not appear so at first. In favor of drift: There were few Neandertals, and the population size of the succeeding Upper Paleolithic, up through the Last Glacial Maximum, was also small—the best estimates are on the order of 2000 people for Western Europe and 5000 for continental Europe to the Urals (Bocquet-Appel et al., 2005). There would have been perhaps twice or more that number across the entire Neandertal range. The effective population size represented by this population would have been smaller; perhaps 3000–5000 for Neandertals and Aurignacian-era people, only half, or around 2000, females. Genetic drift in this small mtDNA population would have been much stronger than for autosomal genes, and very much stronger than in most recent human populations.

But when we plug these numbers into a model of random genetic drift, it starts to appear very unlikely that drift alone could explain the observations. Let’s assume (falsely) that our Neandertal genetic samples all dated to 40,000 years ago, and the female effective size was 2000 individuals between then and 15,000 years ago, and that the population of Neandertal country were a random mating pool. Following these assumptions, on averageall the mtDNA genomes at 15,000 years ago would descend from only 4 or 5 ancestral copies in the population 40,000 years ago. If these five ancestral copies were, by chance, a different haplogroup from the 15 copies we’ve already found, then drift could explain the data.

However, this still doesn’t appear very likely. So far, every one of the Neandertals shares a single haplogroup. The frequency of this haplogroup was apparently very high, making it very unlikely that all five ancestral copies would have belonged to some other haplogroups of which we have never found any trace.

Notice that this argument does not depend very much on the number of Neandertal mtDNA sequences that we have found. The fact that there are 15 helps to constrain the frequency of the haplogroup within the population 40,000 years ago, in our model. That frequency is unlikely to be less than around 85%, assuming random sampling. But suppose there were only five. We would still know that the Neandertal haplogroup was very common in its population, even if we thought it was only 50%. It would still be unlikely to draw four or five ancestral copies and have all of them be some other haplogroup that we haven’t found.

This gives us a considerable confidence margin against drift. We need it. After all, the Neandertals were not randomly sampled at a single time, and it is possible that some of them actually carried a human-like mtDNA sequence, which we now falsely interpret as contamination. But even with these shadows hanging over us, it would still be unlikely that none of the ancestors of today’s mtDNA variation were like the Neandertal haplogroup.

Also, the population was not a random-mating pool. When we add geographic structure to the story, which tends to reduce the importance of genetic drift, we find that the possibility that drift alone is almost zero, and it remains very unlikely that a single migration of modern humans interbreeding with Neandertals under random drift could explain the observations, either (Currat and Excoffier, 2004).

Extinction

It is at this point that most geneticists turn to the hypothesis of complete Neandertal extinction. They have a point. Genetic drift apparently cannot explain what we have observed, In their point of view, if genetic drift alone cannot explain the Neandertal mtDNA disappearance, then the only other random process at hand is extinction.

I think that hypothesis is false. It does not account for morphological similarities between Neandertals and later people, genetic evidence that suggests a strong ancient population structure with introgression, or with the apparent behavioral continuity in the Upper Paleolithic.

Happily, I don’t have a commitment to random processes. Instead, I think that the mtDNA evolution of Europe was driven by nonrandom processes of demographic turnover and selection.

Demographic turnover

Here we come to an important point. No one believes that later Europeans evolved from earlier Neandertals by a random process of genetic drift. Yet that is precisely the hypothesis that most studies have set up to refute. Without question it is valuable to set up boundary conditions under the hypothesis of random genetic drift. But the time has come to investigate more interesting models.

Personally, I am surprised that more complicated metapopulation dynamics have not gotten more attention as an explanation for the Neandertal mtDNA results. Population sources and sinks are a hot topic in biology, and you would think that anthropologists would have picked up on this. To my knowledge, the only time anyone has examined a population sink model was in 2001, when Milford Wolpoff and I worked with mathematician Per Enflo on such an idea for Neandertals (Enflo et al., 2001). This idea deserves a fuller treatment (I think I’ll suggest it as a project for one of my classes this year!).

In a nutshell, a population sink is a region where the average rate of reproduction is below replacement levels. This region can remain populated only if individuals migrate in from other places. The places that reproduce above replacement are called population sources. The continual migration from sources to sinks creates a genetic gradient. Individuals sampled at any given time in the population sink are overwhelmingly likely to have ancestors not in the sink but in one or more source populations.

Europe today is a population sink. The population of the continent does not produce enough children to replace itself, and immigration from other parts of the world is high. There are several reasons to suggest that Europe may have been a population sink in prehistory as well. In Neandertal and Upper Paleolithic times, climate fluctuations created unique challenges in Europe, where caloric expenditures were high and food harder to obtain than some other regions.

Continual migration into Europe would provide a simple explanation for why none of today’s mtDNA haplogroups derive from the European Neandertals. The mtDNA population of 15,000 years ago had a few ancestors 40,000 years ago, and none of these ancestors lived in the sink population—all came from the source population in Africa or West Asia. The Neandertal mtDNA variation would have been a short-lived phenomenon, continually being turned over from source populations. Some Neandertal genes would have survived in Europe for hundreds of thousands of years, but some would have come in with more recent migrants from the population source.

There are points that argue against this source-sink hypothesis. The Neandertal-human divergence time for mtDNA is not very different than that estimated for the autosomal genome. If a European population sink had made genetic drift more powerful, that should have affected mtDNA more than the autosomes, so we might expect a more recent mtDNA divergence. Still, there is nor reason why the source-sink dynamic need have been constant over Neandertal evolution, and there may have been multiple sources in the Pleistocene, not only Africa and West Asia. Investigating the boundary conditions of the source-sink model and its correspondence to autosomal genetic results would be helpful.

I should note that mtDNA is not special. Neandertals had lots of traits that are now very rare. The horizontal-oval, or “bridged” mandibular foramen is a prominent example. Out of the relatively small sample of Neandertal mandibles, half have this derived form. Fewer than one percent of recent European mandibles have this form. As for mtDNA, a once-common variant is now very rare. And as for mtDNA, we deserve some explanation. A source-sink model would appear consistent with the continued evolution of such traits during the Upper Paleolithic—a time when the extinction and replacement hypothesis predicts no change in these characters.

Natural selection

The other nonrandom hypothesis is natural selection, which would presumably have favored one or more modern human types while eliminating the original Neandertal haplogroup. I won’t say much about that hypothesis here, since I discussed it in my initial post about the whole-mtDNA-genome sequencing. Selection has a leg up over the other hypotheses now because it seems like there’s good evidence it happened.

Still, selection on mtDNA alone could not explain the total pattern of observations about Neandertals. Physical traits that were once frequent in Neandertals were much less common or absent in later Europeans, and some continued to reduce in frequencies over time. To explain these changes, we must invoke either selection on other traits, or continued demographic turnover in the post-Neandertal population (probably more immigration into Europe) or both.

So selection on mtDNA has never been a sufficient or necessary hypothesis, even if we assume that other genes carried by Neandertals still survive. But given the current evidence that suggests something distinctive about the mtDNA of recent humans, natural selection may receive renewed attention as a factor in the disappearance of the Neandertal mtDNA haplogroup.

References

In the current Cell, the Max-Planck group, in coordination with 454 Life Sciences, report the sequence of a complete Neandertal mtDNA. I'm out of town right now, so I'm writing fairly quickly, and I haven't seen any of the reporting. Keeping that in mind, I wanted to set out a few of the interesting things about the paper.

I've been waiting a long time for this sequence to come out. I know they've had the basic data for a long time, since the mtDNA copy number is very high, the 454 process kicks out a lot of mitochondrial sequence. The reward for the wait is that Green and colleagues have done a very careful job of comparative analysis, with some very interesting results.

If I leave something obvious out, please forgive me, since I'm just dashing this as quickly as I can.

Where we left off...

All previously reported sequences of Neandertal mtDNA have been fragments of the control region. The control region of the mtDNA (hypervariable regions I and II) is very helpful for working out phylogenetic relations among recent humans. True to its name, it varies a lot, and its high mutation rate allows a fine discrimination among lineages that have differentiated only within the recent past.

The high mutation rate of the hypervariable regions also means that closely related populations have accumulated many differences. That's very convenient for identifying Neandertal mtDNA, where only small fragments (up until recently) have been practical to obtain. A small fragment of the mtDNA control region is sufficient to assess whether a specimen is like other known Neandertal sequences or not. Up to now, this has been an important way of authenticating Neandertal DNA sequence results --- although it has the obvious drawback that it might falsely exclude some genuine sequences that really do look like the modern human form.

So far every Neandertal mtDNA sequence looks like a member of the same mtDNA clade. (More carefully, every specimen with good biological preservation that has produced DNA has yielded at least some mtDNA sequences that form a clade distinct from all recent humans. Others are presumed to be contamination -- which I have no reason to doubt.) No recent human -- out of the many thousands that have been sampled so far -- has produced a mtDNA control region sequence like any known Neandertal. The two populations, so far as we can tell, possessed distinct mtDNA clades.

Divergence time

A complete mtDNA sequence provides a lot of sites, which allows a more precise estimate of the divergence time between recent human and Neandertal mtDNA lineages. The paper reports this time as 660,000 years ago, with a confidence interval from 520,000 to 800,000 years ago. That range of dates substantially overlaps with the prior estimates of divergence time, and is a pretty good match to the initial estimate based on a single HVR1 sequence in 1997.

The availability of a complete sequence has also removed a remaining piece of ambiguity from earlier comparisons. Because the hypervariable regions are so variable, it has always been the case that comparisons of hundreds or thousands of recent humans have included some pairs of individuals who are really divergent in their control region sequences. The result: some people living today are more different from each other than Neandertals are from recent people.

Now, that particular fact is not meaningful in a cladistic sense. Neandertal sequences share derived mutations, as do recent humans. But the concept of a "range" of genetic divergence has confused comparisons. Comparing the control region alone, it may appear that Neandertals were not so very different from living humans, even if they have a few derived mutations that no longer exist. As long as some humans were also very different from each other, it remained possible that the tree had been wrongly reconstructed. An equally parsimonious tree (or even a more parsimonious one) might link the Neandertal clade with some modern human, even if not a recent European. When comparing humans to chimpanzees and more distantly related primates, the hypervariable regions are somewhat saturated with mutations, meaning that parallel mutations between different species are very common. This makes it even harder to reconstruct the tree of mtDNA relationships based on the hypervariable regions alone.

Comparing the complete mtDNA genomes of a Neandertal and many recent humans presents a very different picture. Humans are all more similar to each other, when comparing the complete mtDNA genome, than any human is to a Neandertal. And in fact the Neandertal sequence is three or more times as different, on average, from us as we are from each other. This change from the earlier picture is a purely statistical one: more sites, with a more regular mutation rate. But it makes a clearer picture, and one that supports the phylogenetic model more clearly.

Selection on COX2?

Even though the control region is so helpful for analysis of recent humans, and easy identification of Neandertals, it's only a small fragment of the complete mtDNA. The mitochondrial genome is inherited as a single unit, so different mutations on a single mtDNA are co-inherited with each other. That means that the diversity of the noncoding control region is shaped by both genetic drift (due to demography) and selection. The selection includes purifying selection on coding sites across the entire mtDNA genome, and the possibility of positive selection on one or more ancient mutations.

I believe that positive selection on mtDNA in ancient humans has a lot of indirect support (and I wrote as much here). To give a brief list:

• Mitochondrial haplotypes in living humans correlate with functional variation in disease, longevity, and performance -- all areas that have undergone recent biological shifts in humans.
• Some mtDNA haplotypes in humans appear to have been under recent positive selection, as indicated by their geographic distributions.
• Some mtDNA haplotypes have vastly changed in frequencies within the past few thousand years, as evidenced by ancient DNA samples.
• Nuclear genes involved in mitochondrial function have been under recent positive selection.
• MtDNA from Neandertals is completely absent today, despite the other evidence for genetic survival of that population. This combination is very unlikely if mtDNA was neutral.

So I think that positive selection is not only a reasonable hypothesis, it is extremely likely. But that is not to say that it has been demonstrated. Others might say that my final reason, that positive selection can explain the apparent contradiction between mtDNA and other data (such as skeletal comparisons and apparent nuclear introgression), is a case of wishful thinking. They might argue that all this other evidence of Neandertal-modern gene flow is an illusion, and not a problem to be explained.

I don't think they're right, but in the spirit of honest advertising, that's what they think.

It would be unreasonable for me to expect that a Neandertal mtDNA genome would provide strong evidence of positive selection on the human lineage. Finding such evidence would require repeated selected substitutions, probably within a single gene. Otherwise there would never be statistical evidence of positive selection. The available tests for positive selection in a two-genome (or in this case, two-clade) comparison are very weak.

Only a single selected mutation would be sufficient to explain the complete replacement of Neandertal mtDNA by an advantageous modern human type. No test of selection is powerful enough to refute neutrality based on a single selected site in a comparison of two mtDNA genomes. And repeated selection on a single gene just doesn't seem as likely as one or a few instances of selection, potentially on many mtDNA coding regions.

So imagine my surprise, when reading this paper, when I discovered that they found repeated substitutions on a single mtDNA gene in the human lineage, and statistical evidence of positive selection!

The gene is cytochrome oxidase subunit 2 (COX2). Using the chimpanzee mtDNA sequence as an outgroup, there were 18 human-specific and 20 Neandertal-specific nonsynonymous coding substitutions. Out of the 18 human-specific substitutions, 4 were in COX2. Only three synonymous substitutions occurred in humans for this gene (the ratio 3:4 differs from the ratio for other mtDNA coding regions, 54:14). In contrast, Neandertals had no coding substitutions -- every difference between Neandertal and human sequences is inferred to have occurred in ancient humans. These data are unlikely unless COX2 was recurrently selected in ancient humans.

More evidence will be necessary to establish positive selection. The paper includes multiple comparisons of different genes, so a significant result for this one is necessarily weakened by the multiple-comparisons correction.

But in a very interesting part of the paper, the authors did a functional analysis of the human-specific changes in COX2. Functional analysis of coding sites has come a long way in the last few years. Last fall, we saw it applied to the Neandertal-specific mutation of the MC1R gene. It was the functional analysis that argued that the mutation likely resulted in a red hair phenotype. These functional analyses consider the position of a mutation within the protein sequence, the extent to which that part of the protein interacts with other proteins, and whether the coding changes are otherwise conserved in other species.

Here is the paper's conclusion about COX2:

Another interesting observation is that COX2 stands out among proteins encoded in the mitochondrial genome as having experienced four amino acid substitutions on the modern human mtDNA lineage. Further work is warranted to elucidate the functional consequences of these amino acid substitutions. However, all these substitutions are in regions of the protein that, based on the crystal structure, do not have any obvious function, and they are variable among primates. Hence, they may represent either minor adaptive advantages, perhaps of regulatory relevance, or have no significant functional consequences for mitochondrial function. Unless other evidence for their importance becomes available, we see no need to invoke positive selection to account for the evolution of COX2 on the human lineage (Green et al. 2008:423).

To me, a very persuasive finding is that each of the four human-specific mutations of COX2 is also found in some other primate species. In other words, where humans differ from chimpanzees and Neandertals (and generally, gorillas and orangutans), humans are like baboons or macaques. The authors of the paper read this finding as evidence that the changes have little functional importance. But I see this as a suggestion that these substitutions are functionally salient. Different primates have different energetic and dietary constraints, and it should be no surprise if they exhibit functional convergences in mtDNA. Humans evolved four separate sites, within the last half-million years, to be similar to some cercopithecoids and different from most other hominoids. Neandertals exhibited no evolution in this gene. This makes sense under a hypothesis of mtDNA selection in accordance with functional requirements, which we have good reason to believe were different in humans and Neandertals.

But as the authors say, we need more evidence about the function of these genes. I think the comparative evidence now supports the hypothesis of selection very strongly, and is consistent with the pattern of evidence from the nuclear genome and from the anatomy of early Upper Paleolithic Europeans.

Contamination

This paper advances our understanding of contamination within the Neandertal sequences. The authors acknowledge Wall and Kim's (2007) interpretation of a high contamination rate in the earlier reported nuclear genetic data off the 454 platform, and provide additional information to support a relatively high contamination rate:

Contamination with extant human DNA is the other dominant source of erroneous Neandertal sequences. Given the high coverage and the fact that the best estimate of the contamination rate here is 0.5% (with an upper 95% confidence limit of 0.87%), we do not expect contamination to affect the mtDNA sequence assembly to any appreciable level. Under the assumption that the Neandertal mtDNA sequence is reliable, it is a useful tool for gauging contamination when sequencing the Neandertal nuclear genome. Previously, assays to determine contamination within Neandertal fossil extracts were limited to the HVRI, which carry few positions where extant humans differ from Neandertals. By contrast, the complete Neandertal mtDNA now offers 133 such positions. This enables a reliable estimation of mtDNA contamination by analyzing sequence reads from 454 libraries, rather than by PCR-based assays of the DNA extracts. For example, when we do this in a small preliminary data set initially published from this fossil (Green et al., 2006), 10 of 10 sequences are classified as Neandertal. However, in further unpublished sequencing runs from that library, 8 out of 75 diagnostic sequences derive from extant human mtDNA, suggesting a contamination rate of ˜ 11% (CI = 4.7%–20%). This is in agreement with the suggestion (Wall and Kim, 2007) that contamination occurred in that experiment. That library was constructed outside our cleanroom facility and before the introduction of the Neandertal-specific key, which is crucial for the detection of contamination by other 454 libraries, and was therefore not used for the subsequent Neandertal genome sequencing project (Briggs et al., 2007). However, with the help of the mtDNA presented here, such levels of contamination are now easily detectable from 454 sequencing runs (Green et al. 2008:424).

So the mtDNA from the same sequence library as the previously reported 1 Mb of Neandertal nuclear genome shows a high contamination rate. That's really disappointing, since it means we have no data to work with. We'll just have to wait.

OK, that's all I have time to post; more later...

References:

Green RE and 24 others. 2008. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134:416-426. doi:10.1016/j.cell.2008.06.021

Is there anything surprising about finding the Cambridge Reference Sequence in Paglicci 23?

UPDATE follows at the bottom.

Some months ago I was taking some notes about Neandertal pigment use, drawn from a recent article by Marie Soressi and Francesco d'Errico. I got distracted and didn't finish writing them up at the time.

Recently, a number of readers have asked for my thoughts on the article, "The Mythical Moderns," by Robert Bednarik. It is very much worth doing, particularly since a couple of prominent news articles have returned to the issue of "out of Africa" and modern human origins. I also want to discuss the ongoing debate between Paul Mellars and João Zilhão (and others), which touches on many of the same issues. But it's going to take a lot of groundwork to do a good job reviewing the current state of the science.

So I'm returning to old notes, including these.

Soressi and d'Errico's article (in French) discusses three different kinds of evidence for Neandertal "symbolic behavior" (I'm going to scare-quote this for the time being), including engravings (mainly on bone, but also stone), ornaments, and pigments. The first two are worth separate discussions, and in particular Neandertal pendants and other ornamental objects are reviewed well in other publications. The real feature of this article is its relatively detailed discussion of the authors' work documenting pigment use.

The June Scientific American (no link available) has an article on page 32 about the "therapeutic value of blogging." That's some relief, after the stories a couple of months ago about blogging being potentially deadly.

And it's no small irony, considering that the article I found on the previous two pages had great potential to give me therapeutic opportunities here.

In the article, titled, "Need for speed?" David Biello wrote up some of the human genetics results of the past 6 months, placing them as a point-counterpoint presentation of our acceleration result.

First, he cites Gregory Cochran, who does as good a job explaining our result in one sentence as I've seen:

"We found very many human genes undergoing selection" ... "We believe that this can be explained by an increase in the strength of selection as people became agriculturalists, a major ecological change, and a vast increase in the number of favorable mutations as agriculture led to increased population size."

In that form, it is hard to see how anyone could disagree. Clearly, agriculture was a major ecological shift for humans, and it imposed new selection pressures associated with diet, disease, social organization and other ecological factors. At the same time, the population grew and more people meant more mutations. That's the story; the rest is detail filled in by anthropology, genomics, and math.

Biello then cites another recent study that partially confirms our results. That study, by Lluis Quintana-Murci and colleagues, found a much smaller number of selected genes (55), but what is important is that every one of these genes has an F_ST greater than 0.65. In other words, in every one of these cases, an allele that is vanishingly rare in most of the world has reached a frequency over 80 percent in one population. As allele frequencies go, these are extreme differences -- much, much larger than the average genetic difference between populations, characterized by an F_ST around 0.1. We also found a few such alleles in our survey of selected genes, but the vast majority of genes have not generated such extreme differences in frequency -- mainly because they haven't been around long enough. In other words, the Quintana-Murci study confirms the distribution of positively selected alleles, across the range where it overlaps with other studies, including ours.

Then Biello turns to the doubters. Noah Rosenberg coauthored a study earlier this year that reported polymorphism data from a sample of populations around the world.

"We are a young species," remarks geneticist Noah Rosenberg of the University of Michigan at Ann Arbor, who participated in a comprehensive study of genetic variation that appeared in Nature in February. "Different human populations have not been separated for long enough periods of time to develop their own new alleles."

Now, I never hold quotes in the press against people, because they represent a very small portion of what they may have said to a writer, and there are many opportunities for miscommunication. Still, I have to write about this, because it's about my work! So I'll try to describe the misconceptions illustrated by the article.

I am pretty sure that Rosenberg must know that his statement in the article is false. For one thing, "developing" a new allele is simply mutation, and mutation occurs continuously. All human populations have rare alleles that have originated recently and remain distributed only across small areas. Rosenberg's surveys of gene variation have identified many such alleles.

But more important to the current question, positive selection carries an allele to high frequency very rapidly -- much more quickly than the 50,000-year or longer span of time we are talking about. An allele with a five percent fitness edge can go from zero to fixation in several hundred generations -- in humans, they can make very large frequency changes in a thousand years.

If we took the quote at face value, Rosenberg would be saying that human evolution is impossible -- and that new selected alleles like lactase persistence and sickle cell simply cannot exist. We may be a young species (although I would argue the point), but that doesn't mean that we have stopped evolving!

Two prominent geneticists quoted in the article suggest that a bottleneck may explain the pattern of human genetic variation. Here also, I have to be cautious interpreting their quotes -- because even though they may seem relevant, they are referring to their own research papers, which don't actually address the question of linkage disequilibrium and positive selection.

Marcus Feldman suggests that a series of bottlenecks are a likely explanation for the pattern of human genetic variation, in particular, the decreasing gradient of genetic diversity with increasing distance from Africa. This is the "serial founder effect" scenario that I have written about before. I criticized Feldman's and other papers on this subject this spring, referring to "the Stanford school of genetic orthodoxy." My basic point is that all of the results are assumed to support the idea of bottlenecks: no one has yet tested the hypothesis. Even simulations that show the credibility of the concept do not test the hypothesis, because they do not examine credible alternatives, either demographic or selective.

More important, bottlenecks during the dispersal from Africa 50,000 years ago cannot possibly explain linkage blocks concentrated in coding genes with a mean age of 5500 years!

Why is there such difficulty understanding natural selection? I find it quite incredible that many of the scientists who would rail against ignoring Darwin in public schools at the same time actively root out Darwin's theory from their graduate students. Still, there it is. One prominent geneticist (I won't give the name) recently asked me, "You don't really think that lactase was selected, do you?" Many really believe that natural selection has stopped and that recent human evolution reflects nothing more than the cumulative effects of bottlenecks.

What is amazing to me is that these same geneticists embrace hypotheses of population history that cannot possibly have happened. The other geneticists quoted in the article, Carlos Bustamante and his graduate student Kirk Lohmueller, wrote a paper earlier this spring arguing that deleterious mutations have reached high frequency in Europeans (moreso than Africans) because of a bottleneck during European history. The press reported this work as "Whites genetically weaker than blacks, study finds." The hypothesis in the paper is that protein-coding sites otherwise conserved in most mammals may differ among humans because of relaxed selection in a bottleneck.

Here's why they're wrong: their bottleneck is impossible. They propose that the European population was a small, isolated population of 5,700 effective individuals from 214,000 years ago up to the Last Glacial Maximum. I suppose I should take some encouragement that they believe Neandertals were European ancestors (because otherwise, where exactly would this small, isolated population of Europeans have lived). But it's still quite impossible -- it implies no gene flow between Africans and Europeans across that entire span. You see, that is the only way that genetic drift can lead to this kind of result -- large differences in frequencies between continents for hundreds of deleterious alleles. It takes a bottleneck of exceptional length, along with complete isolation.

In what has become a troubling trend, these details were hidden away in the online supplementary information of the paper. It is no surprise that most people read only the paper's conclusions, without critically evaluating the methods. But when the assumptions are hidden so that it takes an effort to look at them, you can understand that the paper does not receive the kind of scrutiny that it deserves. These are not obscure laboratory techniques; they are the basic evidence on which the conclusions were based.

Now, Bustamante knows that positive selection has been very important in recent human evolution, because he wrote an important paper on the subject in 2005. I wrote about the paper at the time -- it was one of the works that really got us thinking about acceleration in the first place. So why in the world did their more recent paper adopt such a ridiculous model of population history?

In any event, I don't think that either of these studies from earlier this year are relevant to our acceleration results. They address different aspects of genetic variation. However, acceleration may help to explain the high frequencies of some gene variants conserved in other mammals -- the results explained by Lohmueller and colleagues as relaxed selection under a bottleneck.

The acceleration of recent positive selection would predict that many otherwise conserved gene variants may be segregating in humans, because they are the targets of positive selection. These conserved sites are among those most likely to show a strong sign of recent selection, because adaptive changes on them are necessarily rare (we know they're rare, because they haven't happened very often among other species). Most such sites are still conserved in humans -- it's just not possible to change their function in adaptive ways. But the massive ecological changes of recent human history have created the opportunity for adaptive responses that are not present in other mammalian lineages. We shouldn't be surprised to see that some such changes are currently underway.

Now, that's a different interpretation of the same data, and it's a testable hypothesis. Are these conserved sites in regions that show other signs of positive selection? If they are, then acceleration explains the data. I'm looking into it now.

If you have a subscription to Nature, you can get a short story from last week's issue, which explores the reaction of a couple of genetics-types to finding Neandertal genes responsible for human mental abilities:

That has to be interbreeding. The earlier studies had missed it because they hadn't considered the changing impact of natural selection over time."

"You can back that up?"

"Absolutely." Beth was always meticulous about her data.

I didn't have to force a smile. "That's fascinating," I said. "It will make Nature for sure." It would get a lot of people hot under their collective collars, but that was fine. Evidence of interbreeding with Neanderthals would create a new paradigm for hybridization being behind the rapid advance of modern humans and make me famous. "What genes are involved?"

Notice: you can tell this is fiction because the result "will make Nature for sure"!

On the other hand, some parts are uncomfortably true-to-life:

"I'm a scientist. I want to know the truth!" More importantly, I wanted to finish the contract; that was my job as principal investigator. I'd always succeeded before; that was why after two decades at the university I was department chair and Beth was still a research assistant.

Yes, the plucky female scientist who believes in the Neandertals is passed over for advancement, while the overbearing man who cares only about grant applications runs the whole department. Well, try to tell me that part is fictional!

It's not that great a story, but the surprise conclusion is exactly what we've been writing -- some aspects of today's human brain biology probably reflect the genetic interactions between Pleistocene human populations. It's neither shocking nor surprising. It's simply evolution!

References:

Hecht J. 2008. The Neanderthal correlation. Nature 453:562. doi:10.1038/453562a

That's the thrust of a technical comment by Graham Coop and colleagues, now online in Molecular Biology and Evolution. The letter refers to the extraction of FOXP2 from two Neandertal specimens from El Sidrón, by Johannes Krause and colleagues, reported last year (I wrote about the paper here).

First, the bad news. The current letter raises the prospect of contamination. Notably, the controls applied by Krause et al. (2007) may be relatively weak evidence against contamination, because of polymorphism within large human comparative samples. The tests rely on the assumption that there is little DNA from living humans in the samples. But if we cannot distinguish Neandertal from human DNA with great accuracy, then we will be mistaken some proportion of the time. Krause et al.'s test, based on derived human alleles absent from the Neandertal genome draft, can still go wrong if the human contaminants happen to have all the ancestral (non-derived) human alleles.

Well, that seems to be the story these days with Neandertal DNA extraction. No test of contamination is good enough. (And remember, that every "test" of contamination is really a procedure for excluding the hypothesis that ancient sequences are identical to recent ones.)

Now, the more interesting news. Coop and colleagues verify that the selective sweep affecting human FOXP2 was indeed recent -- they estimate 42,000 years ago:

To demonstrate this, we estimated the time of the most recent common ancestor (tMRCA) of the selected haplotype (see Figure 1), using an approach sometimes called phylogenetic dating (Thomson et al. 2000; Hudson 2007). This method does not make assumptions about demography and selection, but only requires that the mutations in the intron be neutral or nearly neutral. Taking this approach, we obtained a mean tMRCA of 42 Kya (see SOM for details). While there is considerable uncertainty associated with this estimate, it is surprisingly recent if selection took place over 300 Kya (see SOM). In other words, the selective scenario proposed by the authors cannot account readily for patterns of variation in modern humans. Given that we have no power to detect a beneficial substitution that occurred over 250 Kya, (cf. Sabeti et al. 2006) yet we see a footprint of positive selection at FOXP2, the conclusion of a recent selective sweep at FOXP2 is not surprising (Coop et al. 2008:3-4).

FOXP2 is in one of the ENCODE regions, so its variation is pretty well known. This is not a problematic case: it has a very limited amount of variation around it, and has a strong excess of rare alleles, both signs of a recent sweep.

Coop and colleagues suggest that the beneficial human allele spread into Neandertals (or vice versa) by low levels of gene flow coupled with its selective advantage -- in other words, introgression.

They do allow for an alternative -- perhaps the two amino-acid-coding mutations were not the target of selection, but instead some linked locus. This would not erase the necessity of gene flow from Neandertals, but would question whether this gene flow had involved the FOXP2-language scenario, since it might be some linked gene unrelated to language.

(CORRECTION (2008/04/18): If selection were on a linked site, then Neandertals might share the human-derived amino acids as a result of ancient shared ancestry with humans, while the linked selected sweep might be absent in Neandertals, not necessitating any gene flow.)

I doubt this hypothesis of a linked sweep, since the two sites with human-derived substitutions are otherwise very strongly conserved among mammals. This looks like a credible target for recent selection. But the hypothesis of selection on a linked site cannot presently be tested.

So that's the story. It seems very likely that Neandertals got the language gene from us, or us from them, long after many other genes in the two populations diverged. I write "many" rather than "most" because we haven't really been able to assess the proportion of derived alleles shared by humans and Neandertals. The completion of the draft sequence may help, but I'm afraid that the specter of contamination is going to keep on being raised whenever a part of the Neandertal draft genome looks humanlike.

(via Dienekes)

References:

Coop G, Bullaughey K, Luca F, Przeworski M. 2008. The timing of selection at the human FOXP2 gene. Mol Biol Evol (in press) doi:10.1093/molbev/msn091

Another of the craniometric stories going around this week (Discovery News) proposes that early Levantine modern humans (Skhul-Qafzeh) and Pleistocene Australians come from an early out-of-Africa dispersal that was later mostly replaced by true modern humans (represented by Upper Paleolithic Europeans and living people everywhere). The study is by Michael Schillaci; here's the abstract:

This study examines the genetic affinities of various modern human groupings using a multivariate analysis of morphometric data. Phylogenetic relationships among these groupings are also explored using neighbor-joining analysis of the metric data. Results indicate that the terminal Pleistocene/early Holocene fossils from Australasia exhibit a close genetic affinity with early modern humans from the Levant. Furthermore, recent human populations and Upper Paleolithic Europeans share a most recent common ancestor not shared with either the early Australasians or the early Levantine humans. This pattern of genetic and phylogenetic relationships suggests that the early modern humans from the Levant either contributed directly to the ancestry of an early lineage of Australasians, or that they share a recent common ancestor with them. The principal findings of the study, therefore, lend support to the notion of an early dispersal from Africa by a more ancient lineage of modern human prior to 50 ka, perhaps as early as OIS 5 times (76-100 ka).

But the Skhul-Qafzeh sample and the Pleistocene Australia + Wadjak sample used in the paper (a subset of all the actual specimens) are all males, and the Upper Paleolithic Europeans and recent skeletal samples are (as you might expect) half female.

Seems like a problem....

References:

Schillaci MA. 2008. Human cranial diversity and evidence for an ancient lineage of modern humans. J Hum Evol (in press) doi:10.1016/j.jhevol.2007.10.010

OK, I'm clearly going to have to cut out the beer if I'm going to do anything about stories like this one:

New research led by UC Davis anthropologist Tim Weaver adds to the evidence that chance, rather than natural selection, best explains why the skulls of modern humans and ancient Neanderthals evolved differently. The findings may alter how anthropologists think about human evolution.

Weaver's study appears in the March 17 issue of the Proceedings of the National Academy of Sciences. It builds on findings from a study he and his colleagues published last year in the Journal of Human Evolution, in which the team compared cranial measurements of 2,524 modern human skulls and 20 Neanderthal specimens. The researchers concluded that random genetic change, or genetic drift, most likely account for the cranial differences.

In their new study, Weaver and his colleagues crunched their fossil data using sophisticated mathematical models -- and calculated that Neanderthals and modern humans split about 370,000 years ago. The estimate is very close to estimates derived by other researchers who have dated the split based on clues from ancient Neanderthal and modern-day human DNA sequences.

The close correlation of the two estimates -- one based on studying bones, one based on studying genes -- demonstrates that the fossil record and analyses of DNA sequences give a consistent picture of human evolution during this time period.

"A take-home message may be that we should reconsider the idea that all morphological (physical) changes are due to natural selection, and instead consider that some of them may be due to genetic drift," Weaver said. "This may have interesting implications for our understanding of human evolution."

If you've been reading for long, you might reasonably wonder what I think about this study. My work has shown rapid natural selection in recent humans, consistent with evidence from recent skeletal samples for rapid evolutionary change. So it might seem incongruous that a study could assume that there has been no natural selection on the skeletal traits of recent human populations, and come to any kind of sensible conclusion.

I am actively working on this particular problem, with a manuscript in preparation, so I don't want to comment too extensively. However, I can say a brief word about why I disagree with the analysis.

A model of phenotypic evolution by genetic drift requires an assumption about the effective size of the population (N_e). Weaver et al. (2008) assume a model of "mutation-drift equilibrium." This is an assumption that the effective population size has not changed over time in the populations under consideration -- in this case, the Neandertal and human populations back at least as far as their common ancestor.

In their analysis, Weaver et al. (2008:4647) assume that the effective sizes of the human and Neandertal lineages, throughout the last few hundred thousand years, were equal to 2700 individuals. They wrote this:

The second reference point is the effective population size, PN_e, under a mutation-drift-equilibrium model for sub-Saharan African human populations. Zhivotovsky and colleagues (ref. 17) estimated N_e from 271 microsatellites using an equation equivalent to our Eq. 7 as ≈ 2,700 individuals. Once again, we are just assuming that the morphological and microsatellite estimates should match up under the same model, not that this is the most realistic model to use to infer the actual effective population size.

This is an astounding assumption. It is important because a small effective size allows rapid evolution by genetic drift. But it is contradicted by other evidence.

For one thing, most other sets of genetic data indicate a long-term effective size of at least 10,000 for human populations -- four times larger than assumed in this study. All things being equal, this means that the rate of phenotypic evolution by genetic drift should be four times slower than assumed by Weaver et al. (2008). Some of this difference between real and assumed effective sizes may be washed out by their process of calibration -- their equations involve several unknowns that must be simultaneously estimated, and give a lot of wiggle-room to the results. But that points to another weakness of the analysis -- there's so much wiggle room that almost any level of phenotypic difference might look like "drift."

Moreover, the human population has vastly increased in numbers within the last 50,000 years. Weaver et al. (2008) use the phenotypic and genetic divergences of recent humans to calibrate their "clock" of phenotypic evolution. But the phenotypic divergences between recent human populations, with very large effective population sizes (N_e > 100,000) are simply not comparable to those between Middle Pleistocene humans and Neandertals -- at least, not without taking into account the vast difference in effective population sizes.

But please don't take my word for it. I am a clear partisan on the side of natural selection in recent human evolution. Weaver's quote in the press release above implies that we should accept a pluralistic model, in which genetic drift accounts for some changes. I agree entirely. But their analysis assumes that genetic drift accounts for all changes. I don't deny the role of genetic drift, but I do deny that it explains much about recent skeletal evolution in humans. Random chance cannot do much in a very large population in a few hundred generations.

I really don't understand why you would want to use a heuristic value for effective population size, when it is contradicted by genetic and archaeological evidence. I will be writing about effective population size over the next week, introducing some of the importance of the concept for these kinds of analyses. You're welcome to take a look at what I have to say, and take it or leave it.

Edmund Blair Bolles is reporting from the Evolang conference in Barcelona. Unfortunately I had to cancel my presentation there, but it has been great to read these summaries of some of the papers. I wanted to point readers to his account of Francesco D'Errico's talk:

Neanderthals had language comparable to that of Homo sapiens, Bordeaux-based archaeologist Francisco D’Errico told participants in the Evolang conference in Barcelona this morning (Saturday, March 15, 2008). This claim totally discards the older Big Bang theory that said language arose only very recently (40 to 75 thousand years ago), and also challenges the Out-of-Africa theory that proposes Homo sapiens emerged in Africa about 200 thousand years ago and spread over the rest of the world, carrying language and culture with the, beginning about 60 thousand years ago. A new history will have to be written.

If you have been reading here, you have seen many of the new perspectives D'Errico is talking about, but together they make a very compelling package. Consider:

1. We now know that australopithecines had ape-like vocal tracts, complete with pharyngeal air sacs.

2. We now know that Middle Pleistocene humans (Atapuerca) had humanlike hyoids, unlike australopithecines, so modern human vocal tract anatomy was plausibly a derived feature of Homo, including Neandertals.

3. We have good evidence of pigment use from MSA Africa and Mousterian Europe. The Neandertals in particular appear to have been coloring skin with manganese crayons.

4. Decorative/ornamental artifacts were manufactured both by MSA Africans and Neandertals.

5. Neandertals shared the modern human-derived FoxP2 variant.

I have some notes on D'Errico's work (with Maria Soressi) on Neandertal pigment use that I'll post later. Given the confluence of the recent evidence from genetics, archaeology, and anatomy, I do not see how anyone can maintain the hypothesis that Neandertals (and presumably, other Late Pleistocene humans) did not have language.

Now, that is not to say that they (or any Late Pleistocene humans) were identical in their linguistic adaptations to living or recent people. I still think that communication is the most likely focus of evolutionary change in the Late Pleistocene -- but a change based within a pre-existing community of language users, not a newly-sprung linguistic skill. In fact, I think the next constructive step should be to characterize the variation in linguistic adaptations in recent people, who are surely not identical to each other. That verges on the subject of my presentation, which -- if you attend the AAPA meetings this spring, you will still get a chance to hear. That is, if you stick around until Saturday!

The movie, 10,000 B.C., blew away the competition last weekend, with an estimated $35.7 million in US box office receipts.

I think it is a disaster movie of epic scale -- at least, from the point of view of anthropology!

My favorite quote from a reviewer comes from Peter Canavese's "Groucho Reviews":

It was actually raconteur HL Mencken who said, "No one ever went broke underestimating the taste of the American public," but it was P.T. Barnum who lived it, putting over entertaining hoaxes on an eager public. Barnum's modern-day disciple is Roland Emmerich, specialist in the epic of stupidity. For an encore to the global-warming action picture The Day After Tomorrow (in which Dennis Quaid walks -- through a blizzard -- from Washington D.C. to Manhattan), our favorite Teutonic huckster presumes that prehistory means that anything narrative goes: hey, who can prove him wrong?

As narrator Omar Sharif intones at picture's outset, "Only time can teach us what is truth and what is legend." See? If Omar Sharif said it, it must be true!

Oh, that hits a little close to home -- considering the extent to which TV documentaries about archaeology expect us to believe Alec Baldwin's or Liev Schreiber's authoritative-sounding voices. Hey, if they can sell us cars, they can sell us science, right?

But for a little bit lighter view of the movie's reception, we can turn to the movie's IMDB forum (I credit Simon Greenhill with this idea). Or, maybe it makes for an even more depressing picture; I guess it depends on your point of view.

For instance, we have this criticism:

Next is the fact that they did not speak English back then. I am aware that they could have grunted throughout the movie(i.e. Quest for Fire) but common, with the movie goers to day you can barely have a movie that doesn't have explosions or boobs in it do good. It is just unrealistic for the times.

Well, naturally there is an answer for everything:

Plus, consider this: its still EARTH and their descentants several dozen centuries later will be speaking English so it's way less of a stretch than everyone speaking English in STAR WARS which is ANOTHER GALAXY and I don't see the English dissers here trolling the STAR WARS sites.

Point taken. Those who don't question mystical midichlorians are poorly placed to object to anachronistic pyramids.

Of course, any film dealing with prehistoric life may bring out a certain kind of critic. We all know the type:

The correct term is 10,000 BP, before present. I find the term BC, before Christ, extremely offensive. I am an atheist and I do not want to feel obliged to use all this Christian terminology that is being pushed on me 24/7.

Or maybe that wasn't the type of critic you were expecting? Before you head off to set that writer straight, rest assured that a wide array of well-meaning alumni of undergraduate science courses are ahead of you, brimming with variably-accurate news about radiocarbon chronologies.

One might, perhaps, do better, but this forum is not a place for the sane to wander. Consider one hypothesis about the origins of the movie's story:

The idea was that there were these whitish people who both Asian people and white people were related to. In India it's considered that these people founded India as we know it. Anyway, these people were like the elves from The Lord of The Rings. They were vegetarians and even had an organ which allowed a type of psychic communication. The idea of being "psychic" cropped up heavily when these stories were popular in the 1800s, and still it continues today.

White people lost these powers, according to the story, when they mated with people from the mideast. That's because scientists, and this is true, found hybrid Jewish Neanderthal bodies in the mideast. It was concluded that the human race got "devolved" by mixing with the animal people who once lived on Earth.

I'm going to start putting "and this is true" randomly into my blog posts. It will really increase my links from kooks.

Could it get worse? Of course it could: we just need some "anthropologists" to show up and start educating people! Like this:

All human lineages appear to converge on Africa in the distant past. However, 12,000 years ago there were varied races living in widely distributed civilizations all over the world. This film takes place either in Europe or North America (I don't know which), where there would at that time have been no negroids (although in N. America there also would've been no caucasoids).

Or, OOH OOH, this!

Your spoken and stated strident supposition that there totally no "Caucasoids" in North America over 10,000 B.C. is completely in-correct. Are you at all aware of the conversed "Clovis" and supposedly stated "Solutrian" connection? The interest on the internet in this intriguing interelationship is increasing immeasurably since the National Geographic Channel's documentary demonstratably detailing and declaring that the Mammoths were massacred or a mass extinction event by a major mile wide meteor about 10 millenia ago. So, it surely seems the Cacusoids were killed along with the mammoths and the majority of mega-fauna in most of N. America at about 9,700 B.C., basically.

Check out the alliteration there! I can't wait until I get demonstrably detailed and declared -- AND THIS IS TRUE! -- by a major mile wide meteor!

Later, a "history major" shows up to bring sanity to the place:

Any movie about this time period is going to have to be almost completely made up because we know almost nothing about it. Understand? If you think you know something about that time period, (and please, grow up, I'm only talking about cultural history here ok? Not geology, or ancient animals. If you're a geology or ancient animal freak...i don't know what to tell you. Movies in general probably aren't for you, Ok?)...you don't.

Understand? If you know when sabretooths and mammoths ruled the earth, then maybe movies in general aren't for you.

I have to say, I'm increasingly feeling that way....

But there's always hope. Here's another commenter's assessment of the movie:

So boring a caveman could do it.

Julien Riel-Salvatore reviews some reasons why kuru did not wipe out the Neandertals.

I don't have anything to add. The hypothesis comes from a paper in Medical Hypotheses by Simon Underdown; here's part of the abstract:

TSEs could have infected Neanderthal groups as a result of general cannibalistic activity and brain tissue consumption in particular. Further infection could then have taken place through continued cannibalistic activity or via shared used of infected stone tools. A modern human hunter-gatherer proxy has been developed and applied as a hypothetical model to the Neanderthals. This hypothesis suggests that the impact of TSEs on the Neanderthals could have been dramatic and have played a large part in contributing to the processes of Neanderthal extinction.

The short paper is admittedly speculative but quite clear. It does fail to cite the literature about selection on the prion gene, PRNP (I discussed it here in early 2006).

Riel-Salvatore points out all the reasons why it is probably wrong:

1. Neandertals were eating each other 100,000 years before they went away.

2. Neandertals didn't live as long as most humans who develop TSE symptoms.

3. Neandertals lived at much lower densities than the Kuru-spreading Fore people, and it's not credible for them to have spread a prion disease by cannibalism across this space (although, the urine-dispersed CWD seems to do spread pretty well through deer).

4. Non-Neandertals have a clear record of altering human skeletal remains also, including African Middle Pleistocene and early Upper Paleolithic Europeans.

I think these points are fatal to the hypothesis, unless we resort to a different mode of transmission; but in that case there is no reason to suppose that a prion disease would be involved rather than a viral or bacterial agent. I should also mention that despite early claims, there is not any reason now to think that the human prion gene was under long balancing selection.

References:

Underdown S. 2008. A potential role for Transmissible Spongiform Encephalopathies in Neanderthal extinction. Med Hypotheses (in press) doi:10.1016/j.mehy.2007.12.014

I'm just looking through the January/February 2008 Evolutionary Anthropology, which is all about modern human origins in Africa. The special issue resulted from a conference at Stony Brook, along with a few additions to round out the topic.

I'll have some things to say about these articles, but one thing struck me. I'll describe the problem:

Dan Lieberman's paper, "Speculations about the selective basis for modern human cranial form," discusses five categories of functional requirements that might have been involved in the evolution of the "modern" human cranial anatomy. Each of these imposes distinctive requirements on the form of the head -- not all of which are fully understood -- but all of which changed in ways that parallel the basic changes in cranial form of the Late Pleistocene.

But Tim Weaver and Charles Roseman's paper, "New developments in the genetic evidence for modern human origins," claims that the modern human cranial anatomy originated by genetic drift, without any substantial selection:

Evolutionary quantitative genetic analyses, in fact, show that Neandertal and modern human cranial differences can be explained by genetic drift, making it unlikely, at least for the cranium, that modern human anatomical features were spread by natural selection rather than a range expansion out of Africa. An important point is that these analyses do not simply compare the magnitude of the morphological differences between Neandertals and modern humans; they are multivariate tests of how the patterns of covariation across different cranial measurements compare to those expected for divergence by genetic drift. Natural selective hypotheses designed to account for Neandertal and modern human cranial differences would also need to show multivariate consistency with the observed patterns of variation. While it may be possible to imagine natural selective scenarios that mimic genetic drift for a single measurement, such as fluctuating directional natural selection, the scenarios become much less plausible for multivariate patterns of variation (Weaver and Roseman 2008:78).

Both these papers cannot be correct. A full text search of Lieberman's paper does not find the words "drift" or "random," and "neutral" only appears as part of "neutral horizontal axis." Yet Weaver and Roseman cite the neutrality of cranial form as the main evidence against Eswaran's model of an adaptive dispersal of cranial form. According to them, all of Lieberman's "speculations" must be wrong.

I thought maybe I could get some insight into this dilemma by reading Günter Bräuer's paper, "The origin of modern anatomy: by speciation or intraspecific evolution." That title sounds fairly clear -- if we're talking about a speciation of modern humans to explain their anatomy, that sounds like the kind of rapid change that ought to indicate selection of some kind.

Bräuer shows some skepticism toward Lieberman's ideas about cranial evolution:

In my view, Lieberman, McBratney, and Krovitz's interpretation that anatomical modernization can be boiled down to just a few autapomorphies or genetic changes will be difficult to accommodate within the current fossil evidence (Bräuer 2008:27-28).

OK, but does this disagreement mean that Bräuer is likewise skeptical of adaptive hypotheses to explain modern cranial form? Again, a full text search fails to find the words, "drift," "neutral," or "random." But neither does it find the word "selection." Bräuer is concerned with describing the pattern of evolution of the modern human cranial form, but is entirely noncommittal on the question of why it evolved. That would seem to be problematic in itself: wouldn't we expect a different pattern of evolution if natural selection caused the changes, than if genetic drift caused them? Wouldn't the two causes make different predictions about the role of speciation in the process?

I'll have more to write about Bräuer's interesting paper, but on this issue, I think that is all I can extract from it. Osbjorn Pearson's paper, "Statistical and biological definitions of 'anatomically modern' humans," has more to say on the issue. Pearson cites the work that suggests modern human cranial form evolved under random genetic drift, saying:

Ideally, one would like to partition morphological distance into differences due to genetic drift, adaptation, and environmental interactions with ontogeny. Recently, several promising studies have shed light on these issues, including the amount of morphological diversity in recent humans that likely reflects genetic drift and the effects of the toughness of foods on the cranial morphology and occlusion of nonhuman primates, retrognathic mammals (for example, hyraxes), and humans from different parts of the world. Nevertheless, much remains to be done before these relationships become completely clear (Pearson 2008:40-41).

He later suggests (p. 44) that "rapid morphological change due to drift during population bottlenecks" may be involved in the evolution of modern cranial form. On the other hand, Pearson also suggests that "selection for new, advantageous traits or genes, or some combination of the two [selection and drift]" may have occurred. That would seem fairly noncommittal.

However, Pearson's description of the series of events -- a stepwise, sequential series of anatomical changes ultimately in a worldwide context up to and including the Holocene -- seems pretty unlikely to result from genetic drift alone. Indeed, Pearson writes,

In common with many other parts of the world, [African] crania that have dimensions or suites of morphological traits that make them statistically indistinguishable from the living populations appear only during the Holocene (Pearson 2008:45).

If the evolution of modern cranial form is a process that continued into the Holocene, it is quite impossible to have been caused by drift alone, since the effective population sizes of human populations were too large, and drift could hardly have caused a "nearly universal pattern of gracilization" (ibid.). So Pearson's paper certainly heightens the contrast between the adaptive and drift scenarios. If the events are as Pearson describes them, the "genetic drift alone" hypothesis must be false.

Philip Rightmire's paper is about earlier events, and Chris Stringer and Nick Barton's paper is a conference review. That leaves only Ian Tattersall and Jeff Schwartz's paper, "The morphological distinctiveness of Homo sapiens and its recognition in the fossil record: clarifying the problem," to clarify the problem.

Tattersall and Schwartz direct their attention to the kinds of features that are suitable for identifying a species from the fossil record -- uniquely derived features, or "autapomorphies." In their view, species must be accurately diagnosed from sets of specimens ("alpha taxonomy") before any kind of evolutionary hypotheses can be tested.

Because of this, they don't talk very much about the kinds of evolutionary forces that might cause the patterns they see. The paper includes only one reference to "random" and "adaptive," both in a single sentence:

However, there are some materials of this period [the late Middle Pleistocene] that fall outside, but not far outside, the strictest definition of Homo sapiens as based on the living species. Most of these (for example, Border Cave 5, Boskop, Fish Hoek, Klasies River Mouth except for AP 6222, and maybe Cave of Hearths) form a generally poorly dated South African group in which cranial structure largely conforms to the modern Homo sapiens morphology except that, most notably, the bipartite brow and/or the inverted-T-shaped chin are lacking. Do such fossils represent distinctive and now extinct populations of Homo sapiens that lacked two or more of the most striking autapomorphies of the living species merely as a result of random (or even adaptive) population variation? Or did they belong in life to one or more distinctive reproductive entities whose histories did not impinge, at least biologically, on that of today's Homo sapiens? (Tattersall and Schwartz 2008:52, emphasis added)

The bolded sentence is important. Tattersall and Schwartz view adaptive and random variations as equivalent: small changes between populations that may occur even without the kind of significant isolation that would invite a taxonomic interpretation. They contrast these in the next sentence with "distinctive reproductive entities whose histories did not impinge." And they are correct; modern human populations have morphological differences as a result of both selection and drift, and their histories certainly have impinged on each other.

But it makes a difference whether selection or drift was the cause of changes, because selection is more powerful than drift. Weak selection can cause a level of morphological differentiation that would require long isolation by random drift alone. If selection were involved in African regional differentiation, there may be no reason to posit "distinctive reproductive entities whose histories did not impinge" -- in fact, their histories almost certainly would have impinged.

In other words, the relation of the pattern of features to the taxonomic status of the populations depends on the evolutionary forces that generated the pattern.

As Weaver and Roseman note, their hypothesis that modern human cranial form evolved neutrally depends on the pattern of evolution of different features, not the amount of evolution of any single feature. But the amount of evolution must still be explained; under their hypothesis, it must have occurred in small populations over a substantial period of time. In their hypothesis, the cranial differentiation of African late Middle/early Late Pleistocene fossils would have emerged during relatively long periods of parital or complete isolation. Under that hypothesis, Tattersall and Schwartz would be correct to place these fossils into different taxa, only one of which was ancestral to living people -- or at least principally ancestral, allowing for some small amount of hybridization and introgression.

In contrast, Lieberman's adaptive hypotheses are consistent with the evolution of modern human cranial morphology within a broader, larger population. Patterns of selection may explain the variation among the fossils. Today's humans may have emerged from a population with substantial cranial polymorphism. That scenario would seem to be consistent with the patterns described by Pearson -- in which modern human cranial variation does not standardize until very late, perhaps even Holocene times. Only selection could cause this kind of evolution within the large populations of the last 10,000 years, or even within the large populations of the last 70,000 years.

I picked this problem first, because it was the first to stand out to me in the papers. It does seem a fairly glaring contradiction. I don't expect the authors to have noticed the contradiction in advance; I think that they approach the question of human origins from fundamentally different viewpoints.

As you can tell, two of the papers are not concerned with the causes of evolution at all -- their aim is to map the pattern of morphological variation onto putative speciation events. But it seems to me that if we approach the fossil record with the idea that speciation is the major cause of such patterns, then we have already assumed how the evolution happened. It may not have escaped your notice that this is the major reason for disagreement about modern human origins: One group of authors wants to assume the conclusion, foreclosing further discussion.

I don't have any complaints about the papers that were chosen for the issue -- in fact, I'm interested in reading the current opinions of all these authors. So far, I would say that each paper is a well-written expression of its authors' ideas, and I appreciate having all that in one place.

But it does seem a little strange that a special issue devoted to modern human origins in Africa doesn't have more, um, diversity of opinion. Several of the papers discuss multiregional evolution. They apparently believe that it is an important enough viewpoint to include their reasons for disbelieving it. One of the papers (Weaver and Roseman) includes a section about genetic introgression, kindly citing my work. Another (Bräuer) claims that it is reasonable to include all Middle Pleistocene humans in Africa and Europe as part of "one polytypic species, Homo sapiens" (Bräuer 2008:32).

So the work of those of us who write about evolutionary mechanisms seems to be making an impact. Still, it's kind of like "dark matter" -- you only know about the ideas because of their effects on what you can read! In this case, you can read a lot of peoples' opinions about these ideas -- you just can't read them from the people who thought of them.

What boring meetings these must be, with everybody agreeing with each other all the time, and nobody to point out all these contradictions!

References:

Bräuer G. 2008. The origin of modern anatomy: by speciation or intraspecific evolution? Evol Anthropol 17:22-37. doi:10.1002/evan.20157

Lieberman DE. 2008. Speculations about the selective basis for modern human cranial form. Evol Anthropol 17:55-68. doi:10.1002/evan.20154

Pearson OM. 2008. Statistical and biological definitions of "anatomically modern" humans: Suggestions for a unified approach to modern morphology. Evol Anthropol 17:38-48. doi:10.1002/evan.20155

Tattersall I, Schwartz JH. 2008. The morphological distinctiveness of Homo sapiens and its recognition in the fossil record: Clarifying the problem. Evol Anthropol 17:49-54. doi:10.1002/evan.20153

Weaver TD, Roseman CC. 2008. New developments in the genetic evidence for modern human origins. Evol Anthropol 17:69-80. doi:10.1002/evan.20161

What an excellent line from Clive Finlayson, quoted in this story about that high-mobility Neandertal tooth:

Analysis of the tooth -- part of the first and only Neanderthal remains found in Greece -- showed the ancient human to whom it belonged had spent at least part of its life away from the area where it died.

I don't really understand why Neandertal mobility is a controversial topic, although I can attest that it is one. There is no large carnivore or omnivore (and precious few large mammalian herbivores) that aren't very mobile. With this specimen, they determined the ratio of two strontium isotopes (strontium-87 to strontium-86), a ratio that differs across different geographic locations because of soil and bedrock geology. An individual picks up the distinctive strontium isotope ratio of his or her local surroundings through the food chain.

The study has been online for a while; here's the abstract:

We report here direct evidence for Neanderthal mobility through the measurement of strontium isotope ratios in tooth enamel using laser-ablation, which allows us to use much smaller samples than traditional methods. There has been a long-standing debate over the extent of Neanderthal mobility, with some arguing for Neanderthals having a very limited geographic range and others for more substantial, and even seasonal, lifetime movements. We sampled across the enamel of a Neanderthal third molar from the site of Lakonis, Greece, dating to ca. 40,000 years ago. The tooth was found in a coastal limestone cave, yet the strontium isotope values indicate the enamel was formed while the individual resided in a region with bedrock consisting of older (more radiogenic) volcanic bedrock. Therefore, this individual must have lived in a different (more radiogenic) location during this period of third molar crown formation (likely to be between the ages of 7 and 9 years) than where the tooth was found. This strontium isotope evidence therefore indicates that this Neanderthal moved over a relatively wide (i.e. at least 20 km) geographical range in their lifetime.

I can see some rationale for the suggestion that Neandertals weren't very mobile in this context -- for example, they didn't transport shellfish very far inland. Starting from a tooth at a coastal site, you might hypothesize that most of its diet had been local. But there is abundant evidence from other sources that they moved a lot. I wrote about this last year, citing work by Slimak and Giraud that shows transport distances of more than 250 km for some Mousterian artifacts from Champ Grand. Recent hunter-gatherers historically have had very large home ranges, with occasional travel over much longer distances, and a high rate of intermarriage between groups. All of these things can result in people dying at some distance from the place where they grew up.

So I would be amazed if Neandertals weren't mobile enough for an individual to die 20 km from his or her birthplace. I suppose the quote indicates that Clive Finlayson would be surprised, too:

"The technique is interesting, and if we could repeat this over and over for lots of (individuals) then we might get some kind of picture," he said.

"(But) I would have been surprised if Neanderthals didn't move at least 20 kilometers (12.5 miles) in their lifetime, or even in a year ... We're talking about humans, not trees."

Still we shouldn't minimize the result, which really is constrained by the limits on this kind of data. The authors report just a minimum for this individual -- all they are claiming is that the individual's strontium ratio is inconsistent with the local geology, and there is no consistent geology within 20 km. The individual may have come from much further; we cannot say.

In that context, I would suggest that this study is a test of the idea that coastal resources were not used exclusively by coastal-living Neandertals, but that instead wide-ranging groups of Neandertals used coastal resources when they were at the coast. This was the hypothesis advanced by Mary Stiner in her Honor Among Thieves, which documented coastal resource use in the Italian Mousterian.

Maybe it's not too profound, but I think it's an important point to limit the naive interpretation that coastal sites were occupied by "culturally different" groups of Neandertals, or that Neandertals were somehow not behaviorally flexible enough to master the use of different resource bases.

How could I not look at an article headlined, "Coping with the Caveman in the Crib"? It's a health piece by Tara Parker-Pope, profiling "baby whisperer" Harvey Karp:

In his latest book, "The Happiest Toddler on the Block," Dr. Karp tries to teach parents the skills to communicate with and soothe tantrum-prone children. In doing so, however, he redefines what being a toddler means. In his view, toddlers are not just small people. In fact, for all practical purposes, they're not even small Homo sapiens.

Dr. Karp notes that in terms of brain development, a toddler is primitive, an emotion-driven, instinctive creature that has yet to develop the thinking skills that define modern humans. Logic and persuasion, common tools of modern parenting, "are meaningless to a Neanderthal," Dr. Karp says.

Seems a little harsh. Sure, his advice isn't bad -- it turns out we do pretty much the same things with our toddler. But jeez, lay off the Neandertals, dude!

The challenge for parents is learning how to communicate with the caveman in the crib. "All of us get more primitive when we get upset, that's why they call it ‘going ape,' " Dr. Karp says. "But toddlers start out primitive, so when they get upset, they go Jurassic on you."

Yes, it is true that Goodwin acts like a velociraptor much of the time. But definitely not a Neandertal.

Stories about genetics, paleoanthropology, and other stuff have been falling this week faster than I can keep up, but happily I'm not alone. Here are some of the more interesting blog-takes on recent stuff:

Pigment use by Neandertals

Julien Riel-Salvatore writes about recent work by Maria Soressi and Francesco d'Errico establishing that Mousterian pigment nodules were used as crayons:

The reason why this ongoing study is so convincing is that the authors used replicative referents that objectively establish the microscopic and rugosimetric features of blocks of coloring materials worked in different manners and with different tools. This provides an objective baseline against which to compare the characteristics of objects found in assemblages attributed to Neanderthals and to determine whether they bear evidence of having been purposefully manufactured by human action.

I'll write more about this when I get a chance, but Julien's post is valuable and provides translated (from French) excerpts of the relevant papers.

Genetic diversity in African cattle

Razib writes about a New York Times Magazine article that details the cultural and economic pressures around cattle breeding in Uganda. People are bringing in Holsteins, because even though they are finicky in the African climate, they can give as much as 20 times the milk of the native Ankole cattle. The Ankole breed resembles those that American cattlemen would call "Watusi."

Here's a passage from the article:

Not everyone in Uganda, however, agrees that the foreign breeds are an upgrade. President Yoweri Museveni once imposed a ban on imported semen. Museveni belongs to the Bahima ethnic group. When he was a baby, in a sort of Bahima baptism ritual, his parents placed him on the back of an Ankole cow with a mock bow and arrow, as if to commit him symbolically to the defense of the family's herd. Museveni, now in his 60s, still owns the descendants of that very cow, and he retains a strong bond to the Ankole breed. Two years ago, I accompanied a group of Ugandan journalists on a daylong trip to one of the president's private ranches, where he proudly showed us his 4,000-strong herd of Ankole cattle. At one point, a reporter asked if the ranch had any Holsteins. "No, those are pollution," Museveni replied. "These," he said, referring to his Ankoles, "the genetic material is superior."

Razib's comment on another passage:

I guess it's nice that [the author] put quotes around [genetic] dilution, but the rest of the article suggests to me that the author hasn't internalized that genetics is discrete, and that information isn't destroyed through cross-breeding. Rather, it seems that a good program of cross-breeding could result in a superior breeds of Holstein optimally suited to the local climate. That's what happened with indigenous African lineages as they hybridized with introduced South Asian ones 2,000 years ago to produce the Ankole according to the article! This sort of piece in a widely circulated publication such as The New York Times Magazine could have been a serious examination of agricultural and quantitative genetics, and just how much we depend on these unsexy sciences to feed the world. As it is, there's a lot of hand-waving scare-mongering....

The usual argument in favor of preserving diversity of domesticated species is as a hedge against future uncertainties like climate change or novel diseases. Another reason is to preserve local flavor -- that's why people grow "heirloom" vegetables, for instance. But it is quite certain that the pasturage devoted to traditional breeds of cattle well decline if imported breeds provide a net economic advantage. In that case, the best way to preserve diversity is cross-breeding -- which also has the direct advantage of introducing locally adapted genes into the descendants of the foreign breed.

This is what African herders have been doing for thousands of years, as evidenced by the spread of zebu genes across the continent. These European imports are merely the newest version.

What are genetic tests good for?

Hsien-Hsien Lei has an invited post by Ann Turner, noted for her book, Trace Your Roots With DNA. Turner comments on the new genetic tests from deCODEme and 23andMe:

Since I'm interested in genetic genealogy, I am more attuned to the ancestry components of the deCODEme results. The admixture results are interesting to anyone who suspects they may have ancestors from different geographical areas. The detailed chromosome graphs also show the potential for tracing segments of DNA shared with even more distant relatives. For instace, it was recently found that a block carrying a colon cancer gene could be traced back to a couple who arrived in the US in the early 1600's. This sort of thing might very well show up in the "Compare Me" feature.

Evo-devo and its detractors

On the subject of guest posts, Carl Zimmer is running an essay from Jerry Coyne. The essay is a response to a blog post by Olivia Judson, in which she reviewed the ideas of Richard Goldschmidt and suggested that the macromutation theory may be primed for a comeback, using recent results from evolutionary developmental biology (evo-devo) as a jumping-off point. Coyne has been one of the foremost critics of the idea that evo-devo is somehow "changing" basic conceptions in evolutionary biology.

Unfortunately, her piece is inaccurate and irresponsible, especially for a journalist with a strong science background (Judson has a doctorate from Oxford). I've admired Judson's columns and her whimsical and informative book Dr. Tatiana's Sex Advice to All Creation. But this latest posting is simply silly. As an evolutionary biologist, I'm used to seeing our field twisted out of shape to satisfy the demands of journalists who love sensational new findings--especially if they go against long-held Darwinian beliefs like the primacy of gradual, stepwise evolution. But I'm not used to seeing one of my own colleagues whip up excitement about evolutionary biology by distorting its findings.

I have to say I find the entire concept of a "New York Times blog" to be interesting. They have quite a lot of them now, and they are not clearly demarcated from other editorial content at the Times website. That's not a criticism, but it does mean that readers tend to think they come with the full authority of the Times' editors. To me, they read just like any other blog post anywhere, but for a picture of how people perceive their importance, just look at their comment sections.

That was enough in this case to bring Jerry Coyne out of the woodwork. I think his slapdown is a little extreme (Remind me not to get on his bad side!). But Judson was clearly mistaken to equate today's evo-devo results with Goldschmidt's ideas -- a link that evolutionary developmental biologists themselves deny. At any rate, Coyne's forceful advocacy for his point of view makes for good reading, and I would recommend it to anybody interested in where evolutionary developmental biology is going and how it will influence our ideas about evolution over the next few years. Here at Wisconsin I am at one of evo-devo's epicenters, and I can see a number of ways that it may transform our ideas of human evolution. So in that sense, I am more sanguine than Coyne about the prospects for understanding morphological changes with developmental insights. At the same time, I agree substantially that the genetic questions must ultimately be answered in genetic terms.

The discussion in Zimmer's comments section digresses into what Stephen Jay Gould may or may not have thought about saltational changes in evolution. I think that is essentially unenlightening, in the sense that quote-pulling out of Gould can reinforce almost any point of view.

I've been trying to spread the interviews across the field in various directions. I (virtually) talked with Mica Glantz about Neandertals, Adam Van Arsdale about early Homo, and Anne Weaver about human brain evolution, all the australopithephiles in the readership are probably feeling neglected.

So I wrote to Michelle Drapeau, who was very generous in answering questions about her work on the anatomy of early hominids and her recent field work in Ethiopia. Michelle is on the faculty of the Université de Montréal, in the Department of Anthropology. She serves as co-director of field operations in the Bala Paleoanthropological Research Area of southern Ethiopia.

Hawks: I will start out by asking about your dissertation work, which centered on the new partial skeleton from Hadar, A.L. 438-1. How did you get involved in that analysis?

Drapeau: It's a case of being at the right place at the right time. Bill Kimbel and Don Johanson had asked my advisor at the time, Carol Ward, to describe all the postcranial material recovered from the field in Hadar since 1990. Among those specimens was the partial skeleton of A.L. 438-1 which included associated fragments of the humerus, clavicle, radius, right ulna, mandible, and frontal as well as a complete left ulna, right and left second metacarpals and left third metacarpal. Considering the relatively numerous body parts from one individual, Carol thought the specimen deserved a more detailed analysis. I was Carol's Ph.D. student at the time and the 438-skeleton (as we started to call it) appeared like an ideal subject.

Hawks: What did you have to learn to be able to undertake the work?

Drapeau: I had to learn a lot! My master's thesis was in the history of science field, so all the functional anatomy, including the descriptive and compara