out-of-Africa

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

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!

A flush of papers this week (two today in Nature, one tomorrow in Science) describe new analyses of SNPs across the genome. Two of the papers sample SNPs in global samples numbering more than 500 individuals.

This Reuters story by Maggie Fox is typical of the press coverage:

Gene studies confirm 'out of Africa' theories

WASHINGTON - Two big genetic studies confirm theories that modern humans evolved in Africa and then migrated through Europe and Asia to reach the Pacific and Americas.

...

The studies, published in the journal Nature on Wednesday, paint a picture of a population of humans migrating off the African continent, and then shrinking at some point because of unknown adversity.

Later populations grew and spread from this smaller genetic pool of founder ancestors -- a phenomenon known as a bottleneck.

These studies have very, very exciting potential. Here in my lab, we will be immediately using the data from these papers to test hypotheses about recent human evolution.

But it is beyond me to understand why anyone thinks that the "serial founder effect" story is news!

For one thing, the idea is based on 12-year-old research demonstrating that human diversity declines for some genetic loci with distance from Africa. This observation was replicated for genome-wide STR loci in a well-publicized paper three years ago. This paper clearly demonstrated how a model involving a chain of bottlenecks could result in a cline of diversity -- one population leaving Africa, a small group from this population moving to Jordan, another small group moving from Jordan to Mesopotamia, another small group from Mesopotamia to the Zagros, etc.

In other words, there's nothing new here. It's no surprise that genome-wide SNPs and copy-number variants (CNVs) should replicate the pattern already shown for genome-wide STRs.

What's worse, all these papers from the Stanford school of genetic orthodoxy fail to even test the hypothesis! I pointed out this problem three years ago:

The data that the paper attempts to explain are (1) the correlation of genetic distance and geographic distance among human populations, and (2) the decrease in genetic diversity in populations farther from Africa. We may ask, what other hypotheses would explain the same data? And what kind of evidence could test these hypotheses, instead of just asserting that they "match" the pattern of evidence.

One scenario that matches the evidence is multiregional evolution with a recent African dispersal of some adaptive genes. This is the hypothesis presented by Eswaran (2002). The idea is that human populations interacted for a long time in Africa and Eurasia, and that during the Late Pleistocene, adaptive changes within Africa allowed those populations to spread alleles into existing populations in Eurasia. The strength of the "founder effect" in this scenario depends on the genetic structure and selective advantage of the new African adaptive complex. Ramachandran et al (2005) actually cite Eswaran (2002) as an example of a serial founder effect. So the idea that there was widespread genetic movement out of Africa does not necessarily imply an out-of-Africa population replacement. The data do not require a replacement, and some -- even many -- of the genetic variants outside of Africa may have nothing to do with recent genetic movement out of Africa.

A second hypothesis is presented by Templeton (2002), who proposed that several founder effects happened at different times in the Pleistocene, each carrying one or more genetic variants out of Africa. The pattern of genetic variation appears to indicate that some genes left Africa during the Lower or Middle Pleistocene, while others dispersed later, during the Late Pleistocene. For Templeton (2002), this pattern indicates multiple dispersals, none of which was sufficient to wipe out the genetic contribution of earlier dispersals. This scenario also would lead to a pattern of correlation of genetic and geographic distance (because most genes have been affected by isolation-by-distance for a long time), while the recurrent dispersals would explain the decline in genetic variation outside of Africa.

A third hypothesis is that population size was simply greater within Africa than within Eurasia. The smaller population size (along with isolation-by-distance) would explain the difference in genetic variation; the correlation of genetic and geographic distance would be explained by isolation-by-distance. We may consider a fourth hypothesis also: that natural selection has tended to create slightly more genetic uniformity within Eurasia and slightly more genetic diversification in Africa. Such a scenario might be justified on ecological grounds: African populations cover a wider range of ecologies and have historically had a greater exposure to zoonotic disease, for example.

Except for the serial founder effect with population replacement, none of the other hypotheses are mutually exclusive. In other words, some genes might have been influenced by natural selection, most might have been somewhat influenced by differences in population size, but the largest effect might have been recurrent population dispersals.

Reading over the whole post, I think it did a good job of laying out the situation with serial founder effects in 2005, and there is little reason to change it now. Still nobody has tested the model! Again, this is a case of science by consistency -- the results of simulations generate the same kind of correlations as the observed data, so the authors claim support for their hypothesis.

But the necessary test should be carried out by dating haplotypes, finding the ages of "founder mutations" and eliminating the possibility of introgression from ancestral Eurasian populations. One of the key points in my earlier post is that the model proposed by Eswaran (2002) would generate exactly the distribution expected for serial founder effects -- despite the fact that it describes a wave of genetic change within an already-established pan-Old-World population.

This study doesn't support an out-of-Africa migration; it merely assumes it. Now, I'm one who thinks that there was an important trend of strong gene flow out of Africa in the Late Pleistocene. But data showing a correlation between diversity and distance from Africa just cannot show the critically important facts about the timing and magnitude of such gene flow.

Somebody will eventually straighten all this out. What I wonder is why it never seems to be the reviewers!

References:

Jakobsson M and 23 others. 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451:998-1003. doi:10.1038/nature06742

Eswaran V, Harpending H, Rogers AR. 2005. Genomics refutes an exclusively African origin of humans. J Hum Evol 49:1-154.

Ramachandran S, Deshpande O, Roseman CC, Rosenberg NA, Feldman MW, Cavalli-Sforza LL. 2005. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc Nat Acad Sci USA 102:15942-15947.

Templeton AR. 1998. Human races: a genetic and evolutionary perspective. Am Anthropol 100:632-650.

Templeton AR. 2002. Out of Africa again and again. Nature 416:45-51.

I've read through the new paper by Martinón-Torres et al., on Eurasian continuity in the Middle Pleistocene. They've put out an interesting hypothesis, with some support from previous work, but ultimately I think their methods are too weak to test it.

The press coverage of the paper so far (e.g., this AP article) has been a little confusing, because it misses this point: this paper is not about modern human origins, it's about much earlier evolutionary relationships. National Geographic News resorts to the always-safe:

The finding suggests that the hominid family tree could be much more complex than previously thought.

Ah, so that's what it means! More complex than previously thought! Why isn't there ever a story that makes things simpler than previously thought? I mean, isn't it a sign of a failed science if you have to add complexity to your hypothesis every time you make a new observation? It's like Ptolemaic paleoanthropology!

Anyway, enough of that rant. Let's look at what the paper really says, which is much more interesting than the press! Here's the abstract:

A common assumption in the evolutionary scenario of the first Eurasian hominin populations is that they all had an African origin. This assumption also seems to apply for the Early and Middle Pleistocene populations, whose presence in Europe has been largely explained by a discontinuous flow of African emigrant waves. Only recently, some voices have speculated about the possibility of Asia being a center of speciation. However, no hard evidence has been presented to support this hypothesis. We present evidence from the most complete and up-to-date analysis of the hominin permanent dentition from Africa and Eurasia. The results show important morphological differences between the hominins found in both continents during the Pleistocene, suggesting that their evolutionary courses were relatively independent. We propose that the genetic impact of Asia in the colonization of Europe during the Early and Middle Pleistocene was stronger than that of Africa.

OK, so this is about the initial colonization of Europe and the subsequent evolutionary trends in Europe, Asia, and Africa. The observation is that European teeth show a continued similarity to Asians during the Middle Pleistocene, and there is no evidence that European teeth evolved in the direction of Africans during that time period.

Why is that interesting? Two reasons:

1. The hypothesis directly conflicts with the idea that Middle Pleistocene Europeans were linked to Africans. A large number of anthropologists have been pushing the European-African link, under the old hypothesis that these ancient people belonged to a species that was distinct from East Asians. The European-African clade in this hypothesis is often called Homo heidelbergensis; the Asian clade remains Homo erectus.

2. The hypothesis also seems to conflict with genetic data, which suggest that the relationship of European and African hominids is more recent than the early Middle Pleistocene. In particular, the genetic divergence time between human and Neandertal genomes appears to date to more recently than 700,000 years ago (Green et al. 2006, Noonan et al. 2006), which means that the population divergence must be still more recent. Also, Alan Templeton's papers (e.g., 2002, 2006) claim evidence for migrations from Africa into Europe and Asia during the Middle Pleistocene. Those claims are consistent with the Neandertal genome data, as far as we know it, and they suggest gene flow from Africa into Eurasia.

So, the authors ought to deal with these issues. They do so in their discussion, which in this short paper is one long paragraph. I'm quoting it here in full to comment on the details:

If the population of the Eurasian continent during the Early and
Middle Pleistocene was mainly the result of several out-of-Africa incursions, we should have found African influences in the morphology of the Eurasian populations. However, the continuity of the "Eurasian dental pattern" from the Early Pleistocene until the appearance of the Upper Pleistocene Neanderthals suggests that the evolutionary courses of the Eurasian and the African continents were relatively independent for a long period and that the impact of Asia in the colonization of Europe was stronger than that of Africa.

That is the conclusion of the analysis, in brief. The strength of the conclusion depends on the power of the analytical methods to detect gene flow based on morphological similarities. More on that below.

This finding does not necessarily imply that there was not genetic flow between continents, but emphasizes that this interchange could have been both ways (25, 26).

This seems a little misleading. They have no particular evidence of gene flow from Eurasia to Africa (that would be the "both ways"). Nor do they have evidence in their analysis of gene flow from Africa to Eurasia, after the initial colonization. So they don't have any evidence for gene flow at all. So the finding doesn't emphasize anything about gene flow, other than that the teeth don't show obvious evidence for it.

Around 1 Ma, hominins appear to have dispersed into temperate latitudes as far north as 40 - 45° N (27-29), not only from Africa, but also within Eurasia (29 - 31). These populations were probably descendants of an ancient out-of-Africa exodus, rather than a later one at the end of the Early Pleistocene (30).

This is an important assertion. Other workers have emphasized the similarities of some African fossils to East Asian fossils (mainly from Java, plus Gongwangling in China) in the late Early Pleistocene. That has always been the case with OH 9, and it influenced the description of the Daka and Buia crania as well. The question is how early Asian populations became morphologically distinctive. Here, the authors argue that it was very early, without substantial signs for later interaction, which in the context of the cranial comparisons is now an extreme claim.

In addition, a recent study on the European Lower Pleistocene hominin populations has revealed a possible Eurasian origin for these groups (32).

This refers to the description of the ATD6-96 mandible, which contains an earlier assertion about Asian-European connections. I return to this below.

Furthermore, it has been pointed out that during the Middle Pleistocene there was hardly any faunal exchange bet ween East Africa and the Levant (33) and that the desert between the Sahara and Arabia was an important barrier at that time (26), therefore contributing to the isolation of both continents.

This is an important argument in support of their hypothesis. If movement between Africa and Eurasia was difficult during this time span, that reinforces their claim, and makes it less plausible that there were large-scale dispersals out of Africa during the Middle Pleistocene. That leaves us with a mention of a major exception to their proposed pattern: the evolution of humans in the Late Pleistocene:

With the exception of the SAP [i.e., H. sapiens] out-of Africa dispersion based mainly on genetic data (2), the history of human populations in Eurasia may not have been the result of a few high-impact replacement waves of dispersals from Africa, but a much more complex puzzle of dispersals and contacts among populations within and outside continents. In the light of these results, we propose that Asia has played an important role in the colonization of Europe, and that future studies on this issue are obliged to pay serious attention to the "unknown" continent (Martinón-Torres et al. 2007:3).

The citation of the ATD6-96 mandible leads us to a passage from that earlier paper (Carbonell et al. 2005), which also describes the hypothesis that the founding population of Europe was Asian. Remember that this research group calls the Gran Dolina sample, Homo antecessor, and they initially had written that this species probably colonized Europe from Africa in the late Lower Pleistocene. Here's the relevant paragraph from the cited paper (Carbonell et al. 2005):

The differences in dimensions and robustness between the TD6 mandibles and the East and North African mandibles cast doubt on the African origin of H. antecessor. In contrast, our comparative analysis suggests looking toward the Asian continent. In this respect, it is relevant to mention some data that remained unpublished in 1997, when the new species was named (10), and that are relevant to this discussion. The partial cranium Nanjing I, recovered in 1993-1994 from the Hulu Cave (Tangshan Hill, eastern central China), shows clear modern midfacial traits similar to those observed in the specimen ATD6-69 (19). Wang and Tobias (20) also found similarities between Nanjing I and the Zhoukoudian hominins. Geochronological dates, combined with ecological and paleoclimatic evidence, indicate that the Nanjing skull is ~600 thousand years old (21). Furthermore, the Locality 1 levels at Zhoukoudian, which yielded most hominin specimens, are now considered at least 800 thousand years old (22). Thus, these Chinese hominins may be contemporaneous with or slightly younger than the TD6 hominins. If the Gran Dolina and Chinese populations are phylogenetically related, they should share a common ancestor that also had a modern midfacial pattern and a gracile mandible. In the cranium, this hypothetical common ancestor would have had a low and flat temporal squama, and an unfused styloid process. These traits would have been retained in the Asian hominins but lost in the TD6 hominins, who exhibit a fused styloid process, a convex temporal squama, and probably a significant increase in cranial capacity (19). The Ceprano calvaria (Italy), which has been tentatively assigned to H. antecessor (23), exhibits a convex temporal squama and a cranial capacity of about 1,057 ml (24). Interestingly, TD6 and Zhoukoudian are the only hominins that have a zygomaxillary tubercle before the Upper Pleistocene (19).

So that provides cranial and mandibular evidence of an Asia-Europe connection, supporting the dental evidence provided in the current paper. Still, that evidence is from the initial founding of Europe in the Early Pleistocene and doesn't necessarily apply to the trends during the Middle Pleistocene.

After working through the data supplements for the paper, I think that the analysis is much weaker in statistical power than it could be. In their analysis, they disregard much of the variation within these ancient samples and focus on the differences between samples according to their scoring methods. This may reveal the broad relationships among samples -- if we disregard the possibility of selected parallelisms -- but it does not say anything about the possibility of gene flow among the samples.

Indeed, the result of their analysis (a dendrogram, or branching tree) is quite incapable of showing genetic exchanges at all. It can only show branching events, which means that the result will show either an exclusive relationship between Europeans and Asians, or an exclusive relationship between Europeans and Africans, but never a mixed relationship.

The only result in the paper that indicates a European-Asian relationship is from their cladistic analysis of a subset of the data. And it isn't especially strong evidence, since the Middle Pleistocene Africans are limited to the relatively early sites of Rabat and Tighenif (Ternifine). Granted, the later sample is also small in number, but this isn't really a test of relationships; it's more of a suggestion.

The phenogram inexplicably omits Middle and Lower Pleistocene Africans entirely, and considers only australopithecines and habilines as the African sample.

So, at the moment I consider this to be a very interesting hypothesis in search of a good test. There is no test of gene flow here, just an assertion. Yet, the cranial comparisons give the assertion some plausibility -- and remember, another idea out there is the hypothesis that early Homo originated in Asia and migrated to Africa later.

I think that these topics together constitute the important problem in early human relationships right now, so I'll be writing some more about them. There are many additional interesting facts to consider...

References:

Martinón-Torres M, Bermúdez de Castro JM, Gómez-Robles A, Arsuaga JL, Carbonell E, Lordkipanidze D, Manzi, G, Margvelashvili A. 2007. Dental evidence on the hominin dispersals during the Pleistocene. Proc Nat Acad Sci USA (early) doi:10.1073/pnas.0706152104

Stringer C. 2002. Modern human origins: progress and prospects. Phil Trans Roy Soc Lond B 357:563-579. doi:10.1098/rstb.2001.1057

Rightmire GP. 1998. Human evolution in the Middle Pleistocene: the role of Homo heidelbergensis. Evol Anthropol 6:218-227. doi:10.1002/(SICI)1520-6505(1998)6:6<218::AID-EVAN4>3.0.CO;2-6

Carbonell E and 19 others. 2005. An Early Pleistocene hominin mandible from Atapuerca-TD6, Spain. Proc Nat Acad Sci USA 102:5674-5678. doi:10.1073/pnas.0501841102

Bruner E, Manzi G. 2005. CT-based description and phyletic evaluation of the archaic human calvarium from Ceprano, Italy. Anat Rec A 285A:643-657. doi:10.1002/ar.a.20205

The new Human Origins hall at the American Museum is the occasion for a big Newsweek story, with the tagline, "The New Science of Human Evolution". Author Sharon Begley isn't stingy with the prose:

Whether or not you believe the hand of God was guiding these changes, the discoveries are overturning longstanding ideas about how we became human.

Not that fossils are passé. New discoveries are pruning and reshaping humankind's family tree as radically as bonsai. The neat traditional model in which one species gave rise to another like Biblical "begats" has been replaced by a profusion of branches, representing species that lived at the same time as our direct ancestors but whose lines died out. It's like discovering that your great-great-grandfather was not an only child as you'd thought, but had a number of siblings who, for unknown reasons, left no descendants. New research also shows that "progress" and "human evolution" are only occasional partners. More than once in human prehistory, evolution created a modern trait such as a face without jutting, apelike brows and jaws, only to let it go extinct, before trying again a few million years later. Our species' travels through time proceeded in fits and starts, with long periods when "nothing much happened," punctuated by bursts of dizzying change, says paleontologist Ian Tattersall, co-curator of the American Museum's new hall.

It's a little sad to see the article organized around a 15-year-old storyline. No More Unilineal Evolution! Hey, if it's a "new science", why do we keep hearing from the same old people?

Still, there are some brain evolution subplots, and a few genes mentioned. Aside from the flowery analogies, Begley is a good writer and can capture the essence of most of these stories in a few lines. As an exercise, let's try to take those few lines and change one crucial word to find the weakness of each hypothesis. For each quote, I'll strike out a word in the article and add the correct word in brackets.

You dirty louse

For example, let's start where the article does, with the "body lice = no fur" story:

That fork in the louse's family tree, [Mark Stoneking] and colleagues at Germany's Max Planck Institute for Evolutionary Anthropology concluded, occurred no more than 114,000 years ago. Since new kinds of creatures tend to appear when [correct word: after] a new habitat does, that's when human ancestors must have lost their body hair for good - and made up for it with clothing that, besides keeping them warm, provided a home for the newly evolved louse.

You see how easy that is? Yes, new species adapt to new niches, but there is no reason to think this happens immediately. For that matter, there is no reason to think that hominids lost their fur instantaneously.

And hey, if the theme of the article is that human evolution has lots of extinct branches, then why doesn't that apply to louse evolution? We just saw last week how complex the louse phylogeny has been in hominoids. Who says that the current body louse was the first to fill that niche?

Oh, savanna, don't you cry for me!

Here's a short one:

The apes that stayed in the forests hardly changed; they are the ancestors of today's chimps. Those that ventured into the newly formed habitat of dry grasslands [correct phrase: open woodlands] had taken the first steps toward becoming human.

None of the earliest hominid sites are open savanna. All of them come from sites that preserve other woodland creatures.

By the way, my favorite quote in the whole thing comes here:

Instead, evolution played Mr. Potato Head, putting different combinations of features on ancient hominids then letting them vanish until a later species evolved them.

I just love that analogy! Forget "mosaic evolution". I'm calling it "Mr. Potato Head evolution" from now on.

My what small teeth you have

This part is a little confused:

And it helps explain why Lucy's kind were the way they were. Afarensis women and men stood three to five feet tall and weighed 60 to 100 pounds. They had small [correct: big] teeth good for fruits and nuts, but not meat. (The available prey was [correct: competing predators were] enough to make one a confirmed vegetarian: hyenas the size of bears, saber-toothed cats and other mega-reptiles and raptors.) That suggests that early humans were more often prey than predators, says anthropologist Robert Sussman of Washington University, coauthor of the 2005 book "Man the Hunted." The evidence is as stark as the many [correct: two] fossil skulls containing holes made by big cats and [correct: one containing] talon marks from raptors.

Well, that's taphonomy for you. There is plenty of evidence for predation on ancient hominid bones, and a National Geographic News article from 2002 details work showing the contribution of felids. But only two skulls have holes that may have come from ancient cats (those would be SK 54 from Swartkrans and D2280 from Dmanisi). Only Taung has evidence of raptor damage.

Splitting straws on habiline brains

Dmanisi has left people pretty confused about what explains hominid dispersal from Africa. Some are groping for other hypotheses. Just check out this paragraph:

Erectus shows that brain size is too crude a measure of a species' talents. At Dmanisi, the brains range from 600 to 770 cubic centimeters, comparable to the more primitive habilis. But while erectus did not distinguish themselves in brain size, brain structure is more telling [correct: nor does its brain structure provide any clues]. They were [correct: They were not] the first of our ancestors to have an asymmetric brain, as modern humans do; Australopithecus species do not [correct: did]. Asymmetry is a mark of increasing specialization and therefore complex cognitive ability [correct: of questionable value, since apes and australopithecines have asymmetries to varying extents]. Erectus used it to, among other things, discover and tame fire [add: apparently much later]. What they did not use it for is technology. Tools found with the Dmanisi fossils include cutting flakes, rock "cores" from which flakes were made and a chopper, all primitive even for their time [correct: like those made in Africa]. "The old idea that you needed a master's degree in stone tools to leave Africa is crazy," says Bernard Wood.

Wow, how confusing. The Dmanisi crania had H. habilis-sized brains. They're like KNM-ER 1470. So brain size isn't the key characteristic that allowed hominids to disperse from Africa. Nor is body size, since the Dmanisi hominids were relatively small. That's a genuinely interesting problem.

But asymmetry doesn't solve it. KNM-ER 1470, either Homo habilis or Homo rudolfensis depending on your taste in hominids, has a well-defined Broca's area on the left hemisphere, which I would say is the main informative aspect of asymmetry in fossil endocasts. Chimpanzee brains are asymmetrical in some respects, so "asymmetry" itself is an irrelevant criterion without some specific anatomical feature in mind. The thing that people used to think might be important was petalial asymmetry -- one hemisphere of the cortex shifted forward compared to the other. Early Homo endocranial surfaces show fairly strong petalial asymmetries, including KNM-ER 2598 and KNM-WT 15000. But some Australopithecus endocasts share a similar pattern of asymmetry with later hominids (Holloway and De La Costelareymondie 1982). We don't know how to interpret petalial asymmetry in functional terms, by the way. There appears to be some correlation with handedness, but it's not clear that hand preferences and petalial asymmetries evolved at the same time or for the same reason.

Somebody could write a really interesting story just out of the material in this one paragraph. Just not this story!

Out of Africa

The bottleneck scenario always seems like a hard one for journalists to get right. This article is no better than usual:

Peter Underhill, a molecular anthropologist at Stanford University, tracked 160 such changes in the Y's of 1,062 men from 21 populations across the world. Applying the molecular-clock technique, he concludes that the most recent common ancestor of all men [correct: all Y chromosomes] alive today lived 89,000 years ago in Africa. The first modern humans-and therefore, unlike the earlier wave of Homo erectus into Asia a million years ago, the ancestors of everyone today-departed Africa about 66,000 years ago.

These pilgrims were strikingly few. From the amount of variation in Y chromosomes today, population geneticists infer how many individuals were in this "founder" population. The best estimate: 2,000 men. Assuming an equal number of women, only 4,000 brave souls ventured forth from Africa [correct: were isolated from other humans for thousands of years inside Africa]. We are their descendants.

Hard to get straight: genetic drift takes a long time to fix a gene. We don't necessarily know the number of founders of the out-of-Africa population; what we do know is how many individuals the ancient African population must have had under the hypothesis of genetic drift.

Other genes might well have more recent common ancestors, who would also have been more recent common ancestors of all men. This is especially true if any genes were under selection.

People who see my meetings talk will appreciate the irony of that last sentence...

References:

Holloway RL, De La Costelareymondie MC. 1982. Brain endocast asymmetry in pongids and hominids: some preliminary findings on the paleontology of cerebral dominance. Am J Phys Anthropol 58:101-110. doi:10.1002/ajpa.1330580111

I got the Neanderthals on the Edge volume by interlibrary loan to follow up the Barton shellfish consumption reference. Here is the relevant passage from the discussion of that chapter:

Until recently any discussion of shellfish exploitation by Neanderthals or other archaic humans would have been restricted to just a few exceptional examples. However, following publication of work on the Italian Mousterian by Mary Stiner and others, there are now a growing number of instances where evidence has been documented for deliberate harvesting of marine shellfish resources by Neanderthals. These include cave sites and rockshelters in the Ligurian Riviera (Costa dei Balzi Rossi, Riparo Mochi, Barma Grande), further south in Latium (Grotta dei Moscerini) and in the southern Italian province of Puglia (Grotta dell'Alto, Grotta del Cavallo, Grotta Uluzzo C, Grotta Mario Bernadini, Grotta dei Giganti) (Stiner 1994, fig 6.9). Further afield in Africa similar occurrences have been reported from Middle Stone Age deposits at Blombos Cave in the southern Cape (Henshilwood and Sealy 1997) and at the Haua Fteah in Cyrenaica (Klein and Scott 1986). To these can now be added the localities of Vanguard and Gorham's Caves and the Devil's Tower, Gibraltar. The Gibraltar examples indicate that mussels and otehr shellfish probably contributed regularly to the Neanderthal diet. Furthermore they show that selective use was made of the larger shells collected from estuarine habitats and these small packages of food were carried up to four kilometres to the caves to be prepared and consumed. Much larger accumulations of shellfish in association with the Mousterian deposits are also known from unpublished sites north of Gibraltar near Torrelmolinos, in teh Spanish Costa del Sol (Miguel Cortés Sánchez pers. comm.).

The presence of thin in situ ashy hearth horizons in Vanguard Cave has helped establish that the use of the site by Neanderthals was generally episodic with individual occupation events usually being short-lived. Ephemeral use of this cave is exemplified by the upper hearth and midden which probably represented a single episode of use of no more than a few hours duration. Further down the sequence more intensive evidence of occupation is indicated by accumulations of butchered bones of ibex and red deer but here too the data are consistent with short-term occupational use. In both the upper and middle section of this cave it was noticeable that te hearths were positioned in proximity of hte soutehrn cave wall. Similar juxtapositions have been noted at other Mousterian sites (e.g. Tor Faraj, south Jordan; Henry 1998), but unlike Tor Faraj there is no suggestion of multiple individually spaced hearths. Indeed it is noreworthy that the single hearth in the middle section of Vanguard was re-used at least three times. This may reflect the generally lower density of human groups occupying the site at one time. The position of the hearths near the cave wall and the extensive ash spread in the upper part of the cave may also have been partly connected with sleeping or resting activities. For example in ethnographic contexts, it has been noted that ashy spreads between the hearth and the rock wall may coincide with places where bedding was laid down (Parkington and Mills 1991) (Barton 2000:218-219).

McBrearty and Brooks (2000:511-512) give a long list of MSA and associated sites with shellfish remains (taken broadly to include land snails and tortoises). This is a very long passage, and so I won't quote it, except for the conclusion:

Evidence from coastal Italy (Stiner, 1993, 1994; Stiner et al. 1999) and Gibraltar (Barton et al., 1999) shows that Neanderthals did sometimes eat marine shellfish, but the impressive escargotière at Mumba [Rock Shelter, Tanzania] and the numbers of coastal African sites containing quantities of shellfish seem to indicate a more regular intensive use of small scale resources in the MSA (McBrearty and Brooks 2000:512).

This is certainly one of those where I wouldn't want to have to be the graduate student to test that assertion -- after all, how many coastal Neandertal sites are there? And the occurrence of a unique site where land snails were intensively exploited doesn't seem like the best evidence. Notice how Barton described the relatively nonintensive occupation of the Gibraltar Mousterian caves. It would take some pretty sophisticated sampling to work out whether Neandertals and MSA Africans were significantly different in use of these resources.

Common sense suggests they wouldn't be, at least not without some reason. After all, the other protein-rich foods they had available were vastly more dangerous and risky to acquire. Finding shellfish at coastal sites would seem more like filling an obvious archaeological blind spot than saying something distinctive about resource collection abilities.

But then, the use of shellfish in particular figures into the "coastal dispersal" hypothesis for out-of-Africa. The idea that archaic humans were incapable of exploiting coastal resources is inconsistent with the data. But Paul Mellars (2006) presents a curious alternative view:

The second major factor in stone tool technology lies in the specific functions for which the tools were required. If, as most of the current models suggest, the initial colonization of southeastern Asia and Australasia followed a primarily coastal route (12, 18, 20, 21, 61), then the technologies would be likely to adapt primarily to the exploitation of coastal resources, such as fish, shellfish, and marine mammals (together with tropical plant foods) with perhaps only a minor component of hunting larger land mammals, of the kind that clearly formed a major part of the human economy in both Africa and the whole of western Asia and Europe (21, 59). This would presumably have involved much less emphasis on various forms of hunting equipment (such as spears, meat-processing tools, etc.), as well as equipment involved in the manufacture of elaborate skin clothing, or the construction of tents and other living structures, that were essential to survival in much colder, more northerly environments (59, 62).

In other words, Mellars proposes that southeast Asia and Australasia lost stone tool complexity that would have been present in their African ancestors, because they didn't eat many large land mammals.

This takes shellfish-dependence full circle -- hunters that once took African big game found instead that they could live the easy life following the coast and eating marine resources. Well, maybe -- it still seems like a lot of arm-waving based on distributions that may not be different from each other in any real way.

References:

Barton N. 2000. Mousterian hearths and shellfish: late Neanderthal activities on Gibraltar. In Stringer CB, Barton RNE, Finlayson JC, eds., Neanderthals on the Edge: Papers from a conference marking the 150th anniversary of the Forbes' Quarry discovery, Gibraltar. Oxbow Books, Oxford. pp. 211-220.

McBrearty S, Brooks AS. 2000. The revolution that wasn't: a new interpretation of the origin of modern human behavior. J Hum Evol 39:453-563.

Mellars P. 2006. Going East: new genetic and archaeological perspectives on the modern human colonization of Eurasia. Science 313:796-800. DOI link

The Yearbook of Physical Anthropology has a new review of the genetic evidence for modern human origins by Alan Templeton. The paper is 27 journal pages, and they are full of detail -- especially after the section describing basic coalescent theory.

I'll be going through this paper in the next few days and highlighting some of the issues it raises. In the meantime, here are some quotes from the Washington University press release:

"The 'Out of Africa' replacement theory has always been a big controversy," Templeton said. "I set up a null hypothesis and the program rejected that hypothesis using the new data with a probability level of 10 to the minus 17th. In science, you don't get any more conclusive than that. It says that the hypothesis of no interbreeding is so grossly incompatible with the data, that you can reject it."

...

The new data confirm an expansion out of Africa to 700,000 years ago that was detected in the 2002 analysis.

"Both (the 1.9 million and 700,000 year) expansions coincide with recent paleoclimatic data that indicate periods of very high rainfall in eastern Africa, making what is now the Sahara Desert a savannah," Templeton said. "That makes the timing very amenable for movements of large populations through the area."

Found via Dienekes, who seems to be one step ahead of me this week!

References:

Templeton AR. 2005. Haplotype trees and modern human origins. Yrbk Phys Anthropol 128(S41):33-59. DOI link

I've been trying to think of the best way to approach last week's "serial founder effects" paper by Ramachandran and colleagues (abstract). The paper has been publicized as a support for the out-of-Africa theory.

I always find the science-by-press-release a bit irritating, because it is impossible to examine the claims to see if the data support them. I guess I should adjust my expectations: if there is a press release and no paper yet, I should just assume the data are weak.

The short answer is, the paper doesn't prove out-of-Africa. It doesn't even present any new data that support out-of-Africa. It presents some new simulations of how an out-of-Africa dispersal might work, but it doesn't test those simulations by comparing them to data that might differentiate their preferred model ("serial founder effect") from other hypotheses that might explain the same observations.

In the end, I really don't have a problem with the paper. You see, it doesn't actually mention the words "out-of-Africa". It doesn't claim to support out-of-Africa. All it does is show a correlation between their simulation results and some genetic data. Personally, I wouldn't have written the paper without testing the hypothesis with data that might refute it, but that's just me.

Of course I'm very interested in modern human origins and genetic information about the subject, so I'll try to give a record of my thought process. I include some discussion of isolation-by-distance as a model for genetic variation, different scenarios that would produce the pattern, and the kind of data that would test those scenarios.

The press

What I could find out last week at this time came from the press, much of which can be traced to the October 18 University of Michigan press release:

Small groups of settlers expanding outward from Africa are the most likely progenitors of the modern human population worldwide, according to a new study by researchers at the University of Michigan and Stanford University.

This led to a National Geographic News article on the same date, which says this:

"When we searched over 4,000 points around the world, we found that no point outside of Africa had as high a fit as any point inside of Africa," [University of Michigan geneticist Noah] Rosenberg said. "So this seems to support an 'Out of Africa' historical model for human evolution."

Genetic diversity is highest, and thus oldest, in Africa. This fact has led many geneticists to point to the continent as the birthplace of humankind.

A Discovery Channel news brief picked up the story October 21, starting like this:

Modern humans left Africa in waves and colonized the Mideast first and then Europe, according to a new study that traced early human migration patterns through variations in DNA.

The study, which supports the "Out of Africa" theory that humans first emerged in Africa before migrating to other parts of the world, determined that South America was the last settled region.

But these were the only two news sources to bite, apparently. That itself is usually a bad sign -- "supports out-of-Africa" tends to gather more press attention.

The paper

The paper itself appeared in PNAS Early Edition on October 21, three days after the press release. A text search shows no mention of "out of Africa". Or "recent African origin". Or anything of the sort.

Hmmm.... I'm confused.

The dataset in the paper includes 783 microsatellites sampled in 1027 individuals from different source populations. Like many other genetic samples from humans, this sample has two notable characteristics: overall variation is higher within Africa than elsewhere, and geographically distant populations are more genetically different than geographically close populations. This correlation of geographic distance and genetic difference is often related to the model of "isolation-by-distance", in which the movement of individuals between populations is a function of distance.

Isolation-by-distance

Isolation-by-distance makes perfect sense for human populations. Historically, people have tended to mate with other people close to them, and the chance that they will move a long distance to mate is much less than the chance they will move only a short distance. But isolation-by-distance is no support for any kind of recent mass migration, out of Africa or anywhere else. People could have always lived where they are now, and the genes would still show isolation-by-distance.

There is a long story here that is increasingly only of historical interest. During the early 1990's, a series of comparisons of genetic variation in Africa versus variation in Europe and Asia made a really bad assumption -- they assumed that people in these regions never interbred with each other. If this were true, and if none of the differences between these populations were the result of natural selection, then you could figure out how long ago these "separate" populations must have shared a common ancestry. These studies were among the earliest supports for the idea that modern humans had a recent African ancestry -- owing to the fact that the "date" of population divergence between Africans and non-Africans was between 50,000 and 100,000 years ago or so. By the late 1990's, there were studies that tried to trace the population history within China, or Europe, or Africa using the same methods. Assume the populations never interbred, work out the dates, and presto! There's your population history.

Of course, the assumptions behind these estimates were basically bunkum. A global correlation of geographic distance and genetic difference is compatible with lots of hypotheses of population history -- from long-term isolation-by-distance to "demic diffusion" to recent mass migrations. But what it is not consistent with is a complete lack of interbreeding among human groups. And when you examine the "fit" between these "tree" models of population history (the no-interbreeding models) and real genetic data, you find that they just don't fit very well (Templeton 1998 reviews this issue).

So what about those "dates" of population divergences? Turns out they aren't necessarily divergence dates at all. In fact, if you just assume that the populations never diverged but always interbred, the genetic distances can be explained by different rates of migration (Relethford 1995).

This entire controversy consumed a lot of ink (and now pixels), all based on a single faulty assumption.

Subsets of diversity

A better strain of argument was first proposed by Tishkoff et al. (1996). By this time, it was known that many genes were more variable in Africa than elsewhere, and that Native Americans lacked much of the variation present in Eurasia. But in an analysis of linkage disequibrium around the CD4 gene, Tishkoff et al. (1996) showed that diversity itself formed a gradient, or cline, in which some African populations at or near linkage equilibrium, and populations geographically more distant from Africa showed stronger disequilibrium. This mirrored the pattern of variation of mtDNA, and appeared to indicate a contrast: variation was continuous across space, but discontinuous across time. The greater disequilibrium in populations farther from Africa could be explained as a consequence of recent genetic movement (at least of CD4 genes) into those populations from more variable populations.

Several other genes were later found to show similar patterns: variation was high in Africa, and became systematically lower in populations further from Africa. Sometimes this pattern was characterized as "subsets of diversity", in which Eurasian populations contained only a "subset" of the alleles present in Africa. "Subset" was a misnomer for the actual pattern (at least in every case I looked at), since it implied that no uniquely Eurasian variants occur. The actual pattern is generally more complex, with a smaller number of uniquely Eurasian variants (so-called "private" alleles) than African variants, and a greater average age for African variants than for Eurasian variants.

One hypothesis to account for this pattern of diversity is a "serial founder effect". The idea is that a small group left Africa to found a population in West Asia. Then a small group from that population left to found a population in, say, India. Then a small group from India left to found a new population in Thailand. And so on, until the entire world was populated.

Under this hypothesis, a substantial number of African alleles would be left behind in Africa. Even more of these alleles would be left behind in West Asia. More would be left behind in India. In the end, the diversity of populations would reflect the series of founding events that trace their ancestors' movement out of Africa and into the rest of the world. A serial founder effect from Africa across the globe could account for the decline in genetic variation in populations further and further from Africa.

But there is a problem: notice that the serial founder effect, once again, assumes no interbreeding between human groups. If Africans could move out of Africa into West Asia not only 100,000 years ago but every date after that as well, then their alleles ought to be a lot less likely to have been left behind.

Now this problem is not so pronounced as for the model with a small number of branches. With enough steps (i.e. individual founder effects), it is much easier to make a serial founder effect consistent with human variation, which is clinal.

Even better, if you actually channel comparisons of geographic and genetic distances through a small set of "waypoints", you can get the two to match really well. These "waypoints" represent chokepoints of human movement -- that is, you can't get from Asia to Africa without passing near Cairo; you can't get from Asia to Europe without crossing the Bosporus, etc.

Except, well, you can get from Asia to Europe without crossing the Bosporus, if you can go north of the Black Sea. And you can get from Asia to Africa without going near Cairo if, like the Austronesians, you take a boat by way of Madagascar.

All this is just to say, that if you make your model of founder effects complicated enough -- say, by including a huge number of steps -- then you can come close to matching the overall pattern of human genetic variation. But building a complicated model along one set of assumptions (in this case, the idea that all genetic variation can be explained by drift and founder effects) doesn't confirm the hypothesis that this scenario really happened.

Nor does it test other possible hypotheses for human genetic variation.

Other hypotheses

The data that the paper attempts to explain are (1) the correlation of genetic distance and geographic distance among human populations, and (2) the decrease in genetic diversity in populations farther from Africa. We may ask, what other hypotheses would explain the same data? And what kind of evidence could test these hypotheses, instead of just asserting that they "match" the pattern of evidence.

One scenario that matches the evidence is multiregional evolution with a recent African dispersal of some adaptive genes. This is the hypothesis presented by Eswaran (2002). The idea is that human populations interacted for a long time in Africa and Eurasia, and that during the Late Pleistocene, adaptive changes within Africa allowed those populations to spread alleles into existing populations in Eurasia. The strength of the "founder effect" in this scenario depends on the genetic structure and selective advantage of the new African adaptive complex. Ramachandran et al (2005) actually cite Eswaran (2002) as an example of a serial founder effect. So the idea that there was widespread genetic movement out of Africa does not necessarily imply an out-of-Africa population replacement. The data do not require a replacement, and some -- even many -- of the genetic variants outside of Africa may have nothing to do with recent genetic movement out of Africa.

A second hypothesis is presented by Templeton (2002), who proposed that several founder effects happened at different times in the Pleistocene, each carrying one or more genetic variants out of Africa. The pattern of genetic variation appears to indicate that some genes left Africa during the Lower or Middle Pleistocene, while others dispersed later, during the Late Pleistocene. For Templeton (2002), this pattern indicates multiple dispersals, none of which was sufficient to wipe out the genetic contribution of earlier dispersals. This scenario also would lead to a pattern of correlation of genetic and geographic distance (because most genes have been affected by isolation-by-distance for a long time), while the recurrent dispersals would explain the decline in genetic variation outside of Africa.

A third hypothesis is that population size was simply greater within Africa than within Eurasia. The smaller population size (along with isolation-by-distance) would explain the difference in genetic variation; the correlation of genetic and geographic distance would be explained by isolation-by-distance. We may consider a fourth hypothesis also: that natural selection has tended to create slightly more genetic uniformity within Eurasia and slightly more genetic diversification in Africa. Such a scenario might be justified on ecological grounds: African populations cover a wider range of ecologies and have historically had a greater exposure to zoonotic disease, for example.

Except for the serial founder effect with population replacement, none of the other hypotheses are mutually exclusive. In other words, some genes might have been influenced by natural selection, most might have been somewhat influenced by differences in population size, but the largest effect might have been recurrent population dispersals.

Now the question is whether other sources of genetic evidence can exclude one or more of these hypotheses. The serial founder effect with replacement is the simplest to test, because it not only makes predictions about the pattern of variation (which Ramachandran et al. (2005) consider) -- it also makes predictions about the date of population movement. If variation outside of Africa is inconsistent with a single dispersal that was very recent, then the recent serial founder effect with replacement must be wrong. So the test of the hypothesis is the date of movement -- if any genes preserve evidence of more ancient population movement than the Late Pleistocene, they reject the recent serial founder effect with replacement.

Ramachandran et al. (2005) do not discuss the date of population movement. There is no occurrence of the words "date" or "age" in the paper. There is one relevant occurrence of the word "time":

There clearly has not been time to reach equilibrium between the extremes of man's inhabited range, or even within continents, in the very short evolutionary history of modern humans (29) (Ramachandran et al. 2005:15945).

I left in citation 29 to point out that it is Cavalli-Sforza and Feldman (2003). In other words, their only citation or mention of "recent" population movement is from themselves!

A review of other recent work shows that many genes don't match the time required by the replacement scenario. Templeton (2002) traces evidence of population movements dating to well over 300,000 years ago, with some evidence of much older movement. Eswaran et al. (2005) argue that the diversity of genes outside of Africa is inconsistent with any recent replacement.

I discussed this evidence in my earlier post on mtDNA selection; the data haven't changed since then. The bottom line is that two pieces of information -- the genetic-geographic distance correlation and the cline of lower diversity out of Africa -- match the replacement scenario with serial founder effects. But other hypotheses also match these pieces of information, and none of them require a recent population replacement. A third piece of information does not match a recent population replacement -- the apparent antiquity of genetic variation outside of Africa. This piece of evidence is the crucial test.

References:

Eswaran V, Harpending H, Rogers AR. 2005. Genomics refutes an exclusively African origin of humans. J Hum Evol 49:1-154.

Ramachandran S, Deshpande O, Roseman CC, Rosenberg NA, Feldman MW, Cavalli-Sforza LL. 2005. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc Nat Acad Sci USA 102:15942-15947.

Templeton AR. 1998. Human races: a genetic and evolutionary perspective. Am Anthropol 100:632-650.

Templeton AR. 2002. Out of Africa again and again. Nature 416:45-51.

I had read this paper by Ruiz-Pesini et al. (2004) before, but the particular combination of factors it suggests came together for me in a new way recently:

Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA

A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences permitted positioning of all nucleotide substitutions according to their order of occurrence. The relative frequency and amino acid conservation of internal branch replacement mutations was found to increase from tropical Africa to temperate Europe and arctic northeastern Siberia. Particularly highly conserved amino acid substitutions were found at the roots of multiple mtDNA lineages from higher latitudes. These same lineages correlate with increased propensity for energy deficiency diseases as well as longevity. Thus, specific mtDNA replacement mutations permitted our ancestors to adapt to more northern climates, and these same variants are influencing our health today.

Here are the final two paragraphs of the paper:

This combination of the increased predilection to energy deficiency diseases, but protection from neurodegenerative diseases and aging is consistent with the expectations for mtDNA coupling efficiency mutations. Uncoupling mutations would reduce ATP production, increasing the probability of energetic failure. However, they would also decrease mitochondrial ROS production by increasing the oxidation of the electron transport chain, thus reducing oxidative damage and apoptosis. This could decrease neuronal and other cell loss, thus increasing longevity.

Our observations support the hypothesis that certain ancient mtDNA variants permitted humans to adapt to colder climates, resulting in the regional enrichment of specific mtDNA lineages (haplogroups). Today these same variants result in differences in energy metabolism and altered mitochondrial oxidative damage, thus affecting health and longevity. Therefore, to understand individual predisposition to modern diseases, we must also understand our genetic past, the goal of the new discipline of evolutionary medicine (Ruiz-Pesini et al. 2004:226).

So in other words, populations in northern latitudes today are enriched for a number of mtDNA haplogroups that are likely adaptive to cold. Today, these haplogroups (as a class) are largely protective against degenerative diseases of aging, possibly because they reduce oxygen free radical production. But they are also more susceptible to disorders of energy metabolism, because they reduce ATP production.

Needless to say, this says some interesting things about the relationship of longevity and energy metabolism in recent human populations.

But at the moment, I'm thinking about Neandertals. They lived in a cold place, but their lifestyle suggests that energy metabolism was at a premium. At the same time, they had a much shorter maximum lifespan than living people. According to the model of mtDNA mutations outlined by Ruiz-Pesini et al. (2004), this would be a very odd combination: cold adaptation today is linked to longevity and lower energy metabolism; Neandertals required high metabolism but had lower longevity.

Those functional considerations alone suggest that Neandertals needed a highly specialized mtDNA type that would have been unlike those of living people.

But additionally, the increase in longevity and difference in lifestyle apparent in later Upper Paleolithic people gives a clear reason for the replacement of the Neandertal mtDNA type. These people lived longer, and they had markedly less energy expenditure than Neandertals did. Their dietary and cultural adaptations would have been much more similar to recent arctic peoples (and indeed, might well have been completely identical to the ancestors of recent arctic peoples).

Would this have been an exceptional event? I don't really think so, because Ruiz-Pesini et al. (2004) outline how similar cold-adaptive mutations occurred in different macrohaplogroups that today are all present at higher latitudes. The occurrence of potentially adaptive mtDNA mutations appears to have been quite a common event throughout human prehistory, because today's haplogroups appear to be separated by many mutations that are adaptive in different contexts.

The situation is reviewed in two papers by Douglas C. Wallace (2005a, 2005b). The thing that surprised me about these two reviews is that they embrace a positive selection hypothesis for mtDNA migration out of Africa. Consider:

This mtDNA history is remarkable for the striking discontinuities that exist in mtDNA diversity between climatic zones. Of the extensive mtDNA variation present in Africa only two mtDNA lineages (M and N) succeeded in colonizing all of Eurasia. Of the plethora of Asian mtDNA types that subsequently accumulated, only three haplogroups (A, C, and D) and much later G came to occupy the extreme northeastern Chukotka Peninsula of Siberia. This strikingly correlation between mtDNA lineages and latitude and climate led to the hypothesis that mutations in certain mtDNAs that decreased the coupling efficiency increased mitochondrial heat production and permitted people to survive the cold of the more northern latitudes (Ruiz-Pesini et al., 2004) (Wallace 2005a:173).

This passage is followed by a section to support it, of which I find several parts very suggestive (my emphasis):

This hypothesis is supported by the fact that missense mutations in mtDNA protein genes show regional specificity. Missense mutations are prevalent in the ATP6 gene in the arctic, in the cytb gene in Europe, and in the COI gene in Africa. Mutations in different ND genes also show regional correlation (Mishmar et al., 2003). Moreover, many of the ancient missense mutations change amino acids that are as highly evolutionarily conserved as are most known pathogenic mutations, yet have been retained in the human population for tens of thousands of years. Hence, they could not be pathogenic in the environment in which they reside, but rather must be adaptive and thus beneficial. Furthermore, an analysis of the missense mutations in cytb of complex III, for which the crystal structure is known, revealed that many of these missense mutations affected CoQ binding sites which would alter the Q-cycle, proton pumping, and thus OXPHOS coupling (Ruiz-Pesini et al., 2004).

Finally, when European mtDNA haplogroups were correlated with longevity and predisposition to Alzheimer Disease (AD) and Parkinson Disease (PD), it was found that mtDNAs harboring uncoupling variants were enriched in the elderly and deficient in AD and PD patients. This led to the conclusion that the uncoupling mutations must enhance the flow of electrons through the ETC keeping the ETC carriers oxidized. This, in turn, reduces the spurious transfer of electrons to O2 thus minimizing ROS production and reducing mitochondrial and cellular damage.

These same uncoupling mutations would also reduce the efficiency of ATP generation which could then exacerbate ATP deficiencies resulting from milder mtDNA mutations. This could account for the predilection of patients with Leber's Hereditary Optic Neuropathy (LHON) that harbor the milder mtDNA mutations to also have haplogroup J mtDNAs which harbor either the np 14798 or np 15257 cytb missense mutations. Thus ancient adaptive mtDNA variants are affecting individual predisposition to degenerative diseases and aging today.

This last one also would apply to milder slightly deleterious mutations of nuclear genomic loci that contribute to mitochondrial metabolism. One might even conclude that today's mitochondrial degenerative disorders may in part be a legacy of ancient adaptive mtDNA variants that no longer exist.

Now, if we seriously accept the hypothesis that human mtDNA variation is regionally adaptive, then we have to conclude that a lot of literature that assumes mtDNA neutrality is just wrong. For example:

1. If mtDNA is neutral, then the dates of mtDNA lineage divergences may tell us about the initial migrations of some human populations. If mtDNA is adaptive to different regions, then the dates of lineage divergences tell us about the times that adaptive mutations occurred.
2. If mtDNA is neutral, then it is surprising that archaic mtDNA variants are gone. If mtDNA is selected, then this is not at all surprising: the current global mtDNA variation is simply the product of the last globally adaptive mutation.
3. If mtDNA is neutral, then it is reasonable to explain the lack of ancestral haplogroup L outside of Africa as the consequence of an out-of-Africa population bottleneck. But if mtDNA is selected, this distribution is explained as Wallace (2005b:376) suggests: many mtDNA lineages may have entered Eurasia, but only a few survived local selection.

Is it possible that there have been no globally adaptive mutations? If the present pattern of variation is fine-tuned to climate and diet, it seems very unlikely that the massive life history, brain, and energetic changes during Pleistocene human evolution had no effect whatsoever.

The present distribution of adaptive mtDNA variants suggests a scenario for the replacement of Neandertal mtDNA. Variants of human mtDNA that appear to be adaptive in Eurasia, and particularly in the northern parts of Eurasia, evolved recently upon an African background. The present variation of human mtDNA is comparatively recent, but it is ancient enough that some of today's variants were segregating within Africa over 100,000 years ago, and the haplogroup M dispersal from Africa appears to have occurred between 60 and 70 thousand years ago. Ultimately these gave rise to European haplogroups H, T, U, V, W, X, I, J, and K (Wallace 2005b), in the time period between 50,000 and 9,000 years ago.

We know that these variants were superior to indigenous European mtDNA variants because the Neandertal mtDNA is gone today. Yet, we must suspect that the Neandertal mtDNA would have been very well adapted to their cold climate and high energetic requirements. The advantages of the incoming African-derived mtDNA variants were great, but they would not have been free of disadvantages -- especially with respect to either cold (which has historically restricted non-European mtDNA haplogroups to the south) or energy metabolism (which currently restricts European mtDNA haplogroups to the north).

Thus, the replacement of Neandertal mtDNA could occur only upon the abandonment of Neandertal lifeways. Only a reduction in energy expenditure and exposure to cold could allow the spread of the African-derived mtDNA variants. Both these changes could be accomplished by a cultural transition, which additionally could increase dietary supply and thereby change selective constraints on energy efficiency.

In this context, it is very significant that the latest Neandertals adopted Upper Paleolithic tool industries and other cultural elements usually associated with modern humans. This cultural transition may have decreased the selective advantages of endogenous European mtDNA variants and allowed the substitution of newer European variants of African derivation. In other words, it may have been the very process of adopting new cultural and demographic patterns that resulted in the selection against old Neandertal mtDNA, even within the European Neandertal population.

So far, I have said nothing of what benefit the African-derived mtDNA variants may have provided. It seems likely that it was not related to cold (considering the Neandertals had plenty of time to become cold-adapted), energy (considering that the Neandertals appear to have had higher total energy expenditure than later people), or diet (since Upper Paleolithic people had broadly similar (if slightly different) diets to Neandertals).

Instead, I would propose that the advantage of the African-derived mtDNA variants was in the one area (out of mtDNA-associated factors) where Neandertals and later humans significantly differ: longevity. It is not at all obvious that living longer is a better adaptation for humans as compared to the shorter lifespan of Neandertals. As a very recent adaptive change, it may have required fairly exceptional demographic conditions, such as large population sizes, a reliance on extensive trade networks, or other behavioral attributes of recent people. Only in such a cultural context can the survival of older individuals provide a fitness advantage to their younger kin.

I do not think that the mtDNA change was the most important one; it probably followed many other genomic changes in favor of longevity. This would be similar to the effect of mtDNA variants in the face of climate or dietary differences today: no population was likely restricted from inhabiting the arctic by the lack of favorable mtDNA variants, but the fast mutation rate of mtDNA ensured that populations living in the arctic quickly gained new adaptive variants for their cold climates. Likewise, other genetic changes that led to a longer lifespan would quickly have led to mtDNA variants adaptive to the new demographic reality. The global human mtDNA variability likely reflects such trailing adaptive mutations. This might imply that the transition to greater longevity or other aspects of modern human life history would have been accompanied by not one, but multiple adaptive sweeps of global mtDNA variation.

References:

Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC. 2004. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303:223-226. Full text (subscription)

Wallace DC. 2005a. The mitochondrial genome in human adaptive radiation and disease: On the road to therapeutics and performance enhancement. Gene 354:169-180. Full text (subscription)

Wallace DC. 2005b. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet (Online before print)

Clifford Jolly's review article in the 2001 Yearbook of Physical Anthropology pretty much covers every aspect for which baboons make an analogy for human evolution. These include Jolly's own "seed-eaters" hypothesis, the implications of baboon diversity for early hominid diversification, the spread of features across geographically dispersed populations, and the implications of baboon hybrids for hypotheses of modern human origins.

Jolly spends a lot of time talking about the implications of hybrid sense and population replacement for the evolution of early Homo. It's interesting in its new thinking, and well worth going over. There's no sense reviewing it all, since you could just read it, but I'm working on modern human origins problems myself right now and found the following passages relevant:

The fragments of Neandertal mtDNA sequence (Krings et al., 1997; Hoss, 2000; Ovchinnikov et al., 2000) suggest the point at which the Neandertal story can be linked to the analogous history of baboons. Discussion of the Neandertal mtDNA sequence has focused mainly on its relatively ancient separation from the root of all extant human sequences, and its implications for a Neandertal genetic contribution to modern human populations. From the baboon (or chimpanzee, or gorilla) perspective, however, the separation is not very ancient. It is comparable to 600 ka divergences between olive and hamadryas baboon mtDNA haplotypes, and much more recent than, e.g., the Guinea-hamadryas split. Mitochondrial diversity in Papio may be analogous to the condition in Homo before the "event" (generally interpreted as an "out-of-Africa" expansion of a relatively small subpopulation) that eliminated most of the diversity from its collective mitochondrial (and Y-linked, and autosomal) gene-pool. Unfortunately, investigation of continent-wide genetic phenostructure in Papio is still in its earliest stages, so we cannot pursue the analogy further in this direction. We can, however, make some suggestions based on work in contemporary zones of hybridization, especially the Awash anubis-hamadryas hybrid zone. For example, we can conclude that unless an undocumented, radical genetic event occurred in the 600 ka since they shared mtDNA ancestry with the Neandertals, premodern humans were certainly able to interbreed with them and produce viable, fertile, offspring, as hamadryas and anubis baboons do (Jolly 2001:198).

Jolly notes that evidence of hybrids may only occur within a hybrid zone itself, which suggests difficulty in examining the existence of such scenarios in fossil contexts.

For the human case, this has an important implication: demonstrating phenotypic distinctness (lack of overlap) of Neandertal
and "modern" samples drawn from areas remote in time and space from the zone of contact does not disprove the occurrence of interbreeding at the interface. It also means that the Lagar Velho child, if indeed it is a hybrid, is a rare and valuable find, even though it is irrelevant to the Neandertal "species question," and does not tell us whether Neandertals (or other "archaic" humans) contributed genes to the Upper Paleolithic, or the extant, human gene-pool. Not that these are equivalent, as is often implied; there was ample opportunity for the loss of a few stray Neandertal genes from European Upper Paleolithic populations when the latter shrank and were replaced by food-producing peoples (Jolly 2001:198-199).

This is probably true from a morphological point of view -- morphological mixture will be evident only at the time and place where different populations were clearly in contact. It is less true of individual alleles or features, which might well intergrade much more extensively depending on their selective dynamics. The least persistent evidence of mixing will be features that are substantially multigenic -- which of course probably includes most of the anatomical features with which anthropologists are familiar. On the other hand, individual features or genes might well be expected to persist long after Neandertals themselves disappeared. This appears to be the case for the features examined by Frayer (1993). In that case, the finding of actual "hybrid" individuals is not so relevant: what is important is the observation of changes in trait frequency within larger, more temporally-dispersed samples.

Jolly later discusses the dynamics of hybrid zones and their application to the discovery of Neandertal-modern mixture:

In the Neandertal case, the fact that the interface moved historically from east to west indicates that the pressure of gene-flow was greater in that direction; if a hybrid zone existed, the genes in it were contributed disproportionately by "moderns." "Neandertal morphological genes" may have been removed by natural selection from a narrow zone of hybridization, or been swamped by differential genetic inflow, or perhaps they simply died out with their carriers without any hybridization at all. Any combination of these factors could have contributed to their disappearance. A much more fine-grained temporal record of the transition would be necessary to decide between these alternatives, and the precise scenario is immaterial both for the eventual outcome, and for the so-called "species question" (Jolly 2001:199)

What is important, and hotly contested, is whether Neandertals (and other archaics) contributed any genes to the gene-pool of the human population who succeeded them. This would imply a
flow of genes from the marginal hybrid zone into the expanding modern population: swimming, as it were, against the tide. The important question is not whether Neandertals could have passed some genes by hybridization to incoming Afro-Arabians; they almost certainly could. It is certainly not the neoessentialist (Cartmill, personal communication) red herring of whether or not they were "really" different species. The important questions are purely empirical: first, whether they actually did contribute any distinctive alleles to the incoming population, and second, whether any of these have survived post-Pleistocene upheavals in the human gene-pool. The first question can only be answered by genetic investigation of the DNA of post-Neandertal fossil humans (cf. Hawks and Wolpoff, 2001); the second by trawling the extant human gene-pool itself (ibid.).

Of course, the question of whether they were "really" different species may be deprecated by those who deal with the fuzzy boundaries between species in nature, but "species" is a term that carries loaded meaning for most biologists. Calling Neandertals a different species is tantamount to asserting their irrelevance to the ancestry of recent humans. This is the point behind the "assimilation" model of human origins -- modern humans actually were a different "thing" than Neandertals, and when the two "came into contact," one group "assimilated" the other. If "assimilation" didn't carry this meaning, there would be no reason to talk about it as a model separate from multiregional evolution, or restricted gene flow and isolation by distance, or "mostly Out of Africa", or any number of other names. All these models agree on the presence of Neandertal genes in later people. Where they disagree is in the emphasis. None of them disagree that Neandertals had an evolutionary history different from other regions. But they disagree about just what kind of history that was. So the question of "species" is a central one, not one that can be shoved under a rug.

From that perspective, the important questions are not merely empirical. They are also conceptual. The "assimilation" model depends on a rather complex conceptual scenario. It envisions the differentiation of Neandertal (along with other archaics) and modern populations over some substantial time. During this time, the evolving modern population within Africa gathered steam for its ultimate dispersal, while the Neandertals and other archaics proceeded along their own unique evolutionary trajectories. Finally, the reestablishment of contact among these populations led to the genetic assimilation of most archaic groups and the establishment of a majority-African gene pool throughout the world. In this hypothesis, the initial isolation (which may have been partial or complete) is essential to the ultimate result. Only if Neandertals had become relatively isolated and divergent could their ultimate assimilation make any sense. Thus, the conceptual basis of Neandertal assimilation is their initial speciation, or if not "speciation" in the formal sense, at least their origin as a distinct population and divergence through substantial isolation.

Now this scenario may or may not have happened; we really don't have the data to test it in comparison to its less conceptually elaborate alternatives. But it is not mindless essentialism to note that this hypothesis depends for its reality on a certain historical identity for Neandertals. This identity is potentially testable. Some may find it distasteful to argue about what a species is, since the concept is so variable and messy in its application to living populations, let alone fossil ones. But that doesn't allow us to avoid the issue: what we call things has meaning, particularly to those outside the intricate details of the fossil record.

Jolly points to the baboon example as having important implications for this case of modern human origins. I agree. However, pointing out the analogy between baboon hybrid zones and the Neandertal-modern transition does not make the latter a case of the former. I have no doubt that Jolly would agree quite fully, but it is worth pointing out nonetheless.

In the meantime, the baboons do give a clear notion of the direction that we should look for evidence of Neandertal-modern interactions:

So far, almost all genetic systems investigated in extant humans show no signs of a Neandertal inheritance, but perhaps we need to be more selective in our search. A moving hybrid zone may leave in its wake a few neutral markers derived from the retreating population (Arntzen and Wallis, 1991), but these are likely later to be eliminated by drift. Most likely to survive and be incorporated are genes for traits strongly favored by local conditions (and "hitch-hiking" markers linked to these). Some years ago, a popular work (Kurtén, 1971) plausibly suggested that Neandertals were blond and blue-eyed in adaptation to cloudy, periglacial Europe, while incoming "moderns" had the darker pigmentation of a subtropical people. Perhaps we should survey nordic Europeans for unusually "deep" diversity in noncoding genetic elements closely linked to loci determining pigmentation... (ibid.).

Of course by the publication of this review, precisely that had been attempted by the survey of MC1R variation by Rosalind Harding and colleagues (2000), finding that the so-called ginger allele may be ancient enough to have come from European Neandertals (reviewed here).

Jolly continues with an interesting hypothesis about possible immunological retentions from Neandertals:

Less fancifully, Parham et al. (1994; and Parham, personal communication) speculatively identified a possible Neandertal legacy: an allele of the human MHC system that is found at low frequency in the old Neandertal range. It is remarkable for its inferred ancient separation from other alleles, which themselves form a tight, young clade. MHC alleles are among the likeliest genes to pass through a semipermeable hybrid zone, since selection favors immunological diversity per se, so if the interpretation is confirmed it would set a likely upper limit on the Neandertal genetic contribution to extant Europeans (ibid.).

Much of interest here from the perspective of interbreeding among archaic human groups. Immensely important stuff, and the earlier parts fo the article are just as essential. Please read it.

On a side-note, I also found this interesting mis-citation of myself:

...the uniquely human, culture-driven, in situ conversion of Neandertals to "moderns" (Hawks and Wolpoff 2001) without any appreciable population movement or "gene-flow" is now hard to reconcile with the rather short timescale of replacement (Churchill and Smith 2001), and has been abandoned by its original formulators (Jolly 2001:198).

Funny, I do remember myself ever writing about the "in situ conversion" of Neandertals without gene flow. Nor do I often see gene flow written with scare quotes, since it is given the chapter in most genetics textbooks. Oh well, the idea that people sneakily abandon their theory is seems to be quite the growing meme lately. I guess the only way to avoid it is to keep oneself from "originally formulating" anything.

References:

Jolly CJ. 2001. A proper study for mankind: analogies from the papionin monkeys and their implications for human evolution. Yrbk Phys Anthropol 44:177-204.

Two papers in the in the current (May 13, 2005) Science and an accompanying commentary focus on the mtDNA evidence relating to human dispersals into South and Southeast Asia. One paper, by Vincent Macaulay (University of Glasgow) and colleagues provides mtDNA sequences from aboriginal populations of the Malay peninsula.

Here's the abstract:

A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated "relict" populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia 65,000 years ago was rapid, most likely taking only a few thousand years (Macaulay et al. 2005:1034).

The second paper, by Kumarasamy Thangaraj and colleagues, covers the mtDNA variation of Andaman Islanders. The abstract is less informative; here's the conclusion:

Our data indicate that two ancient maternal lineages, M31 and M32 in the Onge and the Great Andamanese, have evolved in the Andaman Islands independently from other South and Southeast Asian populations. These lineages have likely been isolated since the initial penetration of the northern coastal areas of the Indian Ocean by anatomically modern humans, in their out-of-Africa migration 50 to 70 thousand years ago. In contrast, the Nicobarese show a close genetic relation with populations in Southeast Asia, suggesting their recent arrival from the east during the past 18 thousand years (Thangaraj et al. 2005:996).

Nicholas Wade has an article about the paper in the New York Times. Here's a great exchange:

There is no evidence of modern humans outside Africa earlier than 50,000 years ago, said Dr. Richard Klein, an archaeologist at Stanford. Also, if something happened 65,000 years ago to allow people to leave Africa, as Dr. Macaulay's team suggests, there should surely be some record of that in the archaeological record in Africa, Dr. Klein said. Yet signs of modern human behavior do not appear in Africa until 50,000 years ago, the transition between the Middle and Later Stone Ages, he said.

"If they want to push such an idea, find me a 65,000-year-old site with evidence of human occupation outside of Africa," Dr. Klein said.

Of course, there is no chance whatsoever that a 65,000 year genetic date is significantly different from 50,000 years. Both the current papers follow a long and dishonorable tradition of not providing any confidence interval for their date estimates. Both papers do provide standard errors -- without explanation, they report different standard errors for the same clades -- but standard errors do not say anything about the real uncertainty in the age estimates. It is not all that easy to figure out what the full range of uncertainty in the estimates may be, since it owes not only to the distribution of uncertainty in coalescence times (which is assymmetrical and skewed toward the high end) but also in uncertainty coming from assumptions like the human-chimpanzee divergence time and adequacy of the sampling scheme. Based on the standard errors alone (ranging around 7,000 years for the clade ages related to the "dispersal"), the 63,000 year date is not significantly different from 50,000 years. The true range of uncertainty is probably far greater.

Now, why wouldn't a reader of the papers know anything about this range of uncertainty? Not only do the papers not report confidence intervals in the text, but also the entire presentation of the data is relegated to the supplementary information online, which for both papers is substantally longer than the text. These are not just data tables, but relatively full literature reviews (as full as they get for these papers) and methods sections. This is a disturbing new trend for Science: reporting only results in the journal, and putting the information necessary to evaluate the results into a secondary source. What if you are asked by a reporter to comment on an article, and they send you an embargoed draft? You don't know enough about the paper even from the full text to evaluate it.

I've been thinking today about "media packaging" of research results, and this strikes me as a pretty stark example. Two papers on a single theme, packaged together with a commentary. Both of the papers make relatively cautious (although not cautious enough in my estimation) interpretations; the commentary is more daring. Media reports focus on the issue raised in the commentary, quoting other scientists who haven't seen enough of the research to be informedly critical. Good science reporters know enough to be skeptical; look where the preceding exchange goes:

Geneticists counter that many of the coastline sites occupied by the first emigrants would now lie under water, because the sea level has risen more than 200 feet since the last Ice Age. Dr. Klein expressed reservations about that argument, noting that people would not wait for the slowly rising sea levels to overwhelm them but would build new sites farther inland.

Dr. Macaulay said genetic dates had improved in recent years, now that it is affordable to decode the whole ring of mitochondrial DNA, and not just a small segment.

But he said he agreed "that archaeological dates are much firmer than the genetic ones" and that it was possible his 65,000-year date for the African exodus was too old.

So in other words, there's no result here. But this only applies to the young end of the range of dates for possible "Out of Africa" migrations -- the end that Richard Klein has been so active in examining. There is no word at all about the older end of the time range in any of the articles, commentaries, or press reports. But just as there is no chance these dates aren't significantly different from 50,000 years, there is likewise no chance they are significantly different from 80,000 years, or probably even 100,000 years. Let's cover the scenario for the initial Out-of-Africa colonization:

The very similar ages of haplogroups M, N, and R indicate that they were part of the same colonization process [see (23)]. This most likely involved the exodus of a founding group of several hundred individuals (27) from East Africa, some time after the appearance of haplogroup L3 85,000 years ago, followed by a period of mutation and drift during which haplogroups M, N, and R evolved and the ancestral L3 was lost. Although the details of this period remain to be elucidated, the next stage is much clearer. The presence in each region of the same three founder haplogroups, but differentiated into distinct subhaplogroups, indicates that there was a rapid coastal dispersal from 65,000 years ago around the Indian Ocean littoral and on to Australasia (Macaulay et al. 2005:1036).

Thus, the initial timing of this putative migration is bounded on the lower end by the 65,000 year dates, and on the upper end by the 85,000 year estimate for haplogroup L3. The standard error on this estimate as reported in the supplementary information is 8,400 years, which means that this date could easily be 20,000 or more years higher than it is. So an ancestry by Skhul and Qafzeh is not excluded by these analyses, either. But the paper does not even raise this issue. More strikingly, the commentary puts the two facts in adjacent sentences without adding them together:

Early humans even ventured out of Africa briefly, as indicated by the 90,000-year-old Skhul and Qafzeh fossils [HN9] found in Israel. The next event clearly visible in the mitochondrial evolutionary tree is an expansion signature of so-called L2 and L3 mtDNA types in Africa about 85,000 years ago, which now represent more than two-thirds of female lineages throughout most of Africa. The reason for this remarkable expansion is unclear, but it led directly to the only successful migration out of Africa, and is genetically dated by mtDNA to have occurred some time between 55,000 and 85,000 years ago (Forster and Matsumura 2005:965).

Ignoring this one, the paper leaves us with these options:

Three possible hypotheses can be distinguished using these data. If modern non-Africans are descendants of populations that dispersed along both northern and southern routes, then mtDNA lineages belonging to relict populations (including Orang Asli, Papuans, and Aboriginal Australians) should diverge from founder types that are distinct from those leading to the main continental Eurasian groups. If there were just a single dispersal, then all non-African populations should diverge from the same set of founders, which would coalesce to 45,000 to 50,000 years ago if the Levantine corridor model were correct, or 60,000 to 75,000 years ago if they were all the result of the proposed earlier single southern route (4). At this time, a northern passage was most likely blocked by desert and semi-desert (26) (Macaulay et al. 2005:1035, citations therein).

Okay, hmm...let me get this straight: modern humans had uber-technology to float across the Red Sea, kill mammoths, and outcompete every archaic human in every ecology they had occupied for a half million years or more, but they couldn't manage to move in 10,000 years across a semi-desert? And let's not forget the "modern" humans that get thrown under the bus in this scenario -- Skhul, Qafzeh, Liujiang -- either they don't qualify as "really" modern, or they've been misdated. Oh, and, there is the slight problem that no other locus provides any evidence of this pattern of population movement -- even the Y chromosome -- and many are not consistent with it.

There is a strategy to deal with these evidentiary problems:

Firm archaeological age estimates are more recent [more ancient dates are simply disregarded in this paper] -- 50,000 years for Australia and ~45,000 years for southeast Asia -- but early evidence may have been lost to sea level rises. Moreover, human populations may then have diffused from the coast into the continental interiors more gradually, leaving a greater archaeological signature on the landscape as they grew in size (Macaulay et al. 2005:1036).

This is always possible, but it can't be a good sign when your hypothesis depends on the same logic as the aquatic ape theory.

A short word about the bottleneck

From the commentary:

One intriguing question is the number of women who originally emigrated out of Africa. Only one is required, theoretically. Such a single female founder would have had to carry the African L3 mtDNA type, and her descendants would have carried those mtDNA types (M, N, and R) that populate Eurasia today. Macaulay et al. use population modeling to obtain a rough upper estimate of the number of women who left Africa 60,000 years ago. From their model, they calculate this number to be about 600. Using published conversion factors, we can translate this estimate into a number between 500 and 2000 actual women. The authors' preferred estimate is several hundred female founders. All such estimations are influenced by the choice of parameters and by statistical uncertainty; hence, it is understood that the true number could have been considerably larger or smaller. Improved estimates will involve computer simulations based on informed scenarios using additional genetic loci (Forster and Matsumura 2005:966).

Gee, are there any other genetic loci that have been examined with this issue in mind? Do any of them agree with a bottleneck reducing human population size to "between 500 and 2000 actual women"? Considering that the answers to these questions are, "yes, many have been examined" and "no, most of them don't agree with that number," what does the full pattern of genetic data say about mtDNA variation?

Earth to Science: what about selection?

Along with the failure to provide confidence limits on estimates, both papers and commentary join another long and dishonorable tradition of completely neglecting the possibility that mtDNA has been affected by natural selection.

There are several ways that selection could affect the interpretations of these papers. My own inclination is to think that an episode of positive selection on human mtDNA explains the its recent coalescence date and the appearance of a rapid dispersal out of Africa. This would be the pattern expected if an advantageous allele appeared within the African population and spread from there through a global human population. The strength of this explanation is that it accounts for why mtDNA looks so different from most autosomal genes in its pattern of variation (c.f. Templeton 2002; Wall and Przeworski 2000).

Now, you don't have to buy into this hypothesis of positive selection to understand that some kind of selection may have severely weakened the ability of human mtDNA to accurately portray ancient population movements. Purifying selection alone would affect these estimates, particularly since they are based on coding region sequences. At the least, small isolated populations may be observed to have a higher effective rate of mutations because of an increased effect of genetic drift against weak purifying selection. At the worst, different environments affecting human groups in the past may have had differential selective effects, with unpredictable effects on the mtDNA phylogeny.

Is this a serious problem? On the one hand, even the maximum degree of purifying selection affecting nonsynonymous substitutions probably affects the apparent diversity of the coding region of the global mtDNA by a factor of two or less. So on the surface, although this might be a fairly big problem, it is somewhat limited in its possible impact. On the other hand, this kind of selection almost certainly occurred. Selected sites in the coding region of the mtDNA are increasingly recognized and known to be common within many human populations. Within just the last week, there has been a new announcement of a common mtDNA variant (haplogroup U) related to cancer risk, and one survey associating mtDNA genotypes with performance in elite athletes (Niemi and Majamaa 2005). Mitochondrial dysfunctions (not all caused by mtDNA genes) are known to increase the risk of Alzheimer's, Parkinson's, ALS, and other neurodegenerative disorders (Zhu 2004). Purifying selection has been an important force on the global distribution of mtDNA (Wise et al. 1998). The presence of mutational variants with such a high selective cost may suggest countervening selective advantages to thse mutations that have not yet been discovered -- in other words, suggesting that not only purifying but also balancing selection may be affecting the frequencies of these mtDNA alleles. So the problem is likely serious, and its full extent is not yet known.

A basic cautionary attitude would indicate that it is no longer tenable to assert that the history of the mtDNA of a population is the same as the history of the population. There are just too many unaccounted variables to believe that methods that assume complete neutrality for mtDNA are giving accurate dates for population movements, expansions, or other events. My favorite quote on the issue is from Razib at Gene Expression:

I am not totally discounting all elements of the narrative pressed forward above, but, genes serve as flexible instructions to shape and mold a human's phenotype, the lineages are all their own, and the concordance of the gene lineages with "individual" lineages, let alone populations, is I think an often tenditiously assumed axiom in many of these research papers. The authors above make the identity of genes:individuals, groups of genes:groups of people. Working back over 2,000 generations with such assumptions is I think a somewhat sketchy proposition unless your variables are controlled for (eg; at least the Andamans are islands, which are noted for fostering relatively genetically isolated people. For example, Sardinia is situated in the rather populous Mediterranean, but it often is an outlier in Principal Component Analysis diagrams of European genetics). Or, if your facts are so crystal clear, the narrative so compelling, the predictions so spot on, than the model is simply self-evidently true. But at this point I think that Recent-Out-of-Africa has depleted all the parsimony capital it had saved up, at least from where I stand.

Selection on mtDNA is not a moribund backwater of research; it is being pursued by groups studying some of the highest-profile diseases. We don't know yet how selection may have affected the full pattern of human variability, but we know enough to know that the answer isn't zero. So why have human geneticists studying global mtDNA variability completely ignored the issue? And what will it t