More on the Neanderthal -- H.s.s. debate.

[Jacques Cinq-Mars]

All,

Here is a paper that is certainly worthy of discussion.

Jacques Cinq-Mars

Neandertals Likely Kept Their Genes to Themselves

PLoS Biology - Volume 2 | Issue 3 | March 2004

Synopsis:

Scientists searching for clues to our origins have long relied on studying fossils to piece together our evolutionary history. Now, with the tools of molecular genetics, they can reach beyond morphological evidence to retrieve traces of DNA preserved in the remnants of bone. And in these ancient DNA sequences, they're finding bits and pieces of the evolutionary record. Over the course of evolution, changes in DNA sequences accumulate at a predictable rate. These mutations can reveal not only how closely related we are but also when evolutionary lineages diverged. Identifying both a typical range of genetic variation and rate of mutation for a given species or population, for example, can serve as a frame of reference for analyzing DNA sequences from other species or populations. Most molecular anthropologists use DNA found in mitochondria—intracellular structures that convert food into energy—to reconstruct human evolution. Distinct from nuclear DNA, mitochondrial DNA (mtDNA) exists in the cytoplasm of a fertilized egg and is passed on only through the maternal lineage.

An ongoing debate about human origins has revolved around the theory that Homo sapiens and Homo Neanderthalensis interbred, since the two species coexisted. Neandertals lived roughly 150,000 to 30,000 years ago, toward the end of the Pleistocene era, and inhabited Europe, parts of Asia, and the Middle East. Modern-day humans arose between 100,000 and 200,000 years ago. Recently, an international multidisciplinary team of scientists led by Svante Pbo of the Max Planck Institute for Evolutionary Anthropology have analyzed the largest sample of Neandertal and early human remains to date and conclude that Neandertals could not have made a significant genetic contribution to early modern humans.

Part of the challenge of resolving the human–Neandertal interbreeding issue stems from the fact that so many fossil samples—of both early humans and more archaic humans—are contaminated with the DNA of the contemporary humans who have handled them. So even if a Neandertal sample contained a “real” (or endogenous) DNA sequence resembling early humans—which would indicate intimacy between the two groups—it might be considered contaminated. When Pääbo and colleagues looked for modern DNA, they found it in every sample they examined: in the Neandertal and early human fossils—and even in cave bear teeth. To circumvent this problem, they looked only for Neandertal mtDNA as evidence of interbreeding. Since it is easy to distinguish modern human mtDNA sequences from the four Neandertal mtDNA samples that have been sequenced so far, the researchers decided to determine whether Neandertal-like mtDNA could be found in other Neandertal fossils as well as in early human remains.
Neandertal skull from La Chapelle aux Saints

As these fossils are precious commodities, Pbo's group applied a technique developed in their lab that uses amino acid content as a measure of extractable endogenous DNA and requires removing just 10 mg of bone from a specimen rather than much larger pieces of bone. Of 24 Neandertal and 40 early modern human fossils analyzed, they found four Neandertal and five early human specimens that passed the amino acid test. These fossils included samples classified as “transitional” between the two groups and represented a wide distribution across Europe, where the two groups would likely have encountered one another. When they analyzed these samples for Neandertal mtDNA, they found mtDNA sequences that are absent in contemporary human mtDNA genes but quite similar to those found in the four previously sequenced Neandertals. They found no Neandertal-like mtDNA in the early human samples.

While the authors explain that it's impossible to definitively conclude that no genetic flow occurred between early humans and Neandertals given the limited number of early human fossils available, they point out that even fossil samples considered as anatomically transitional between modern humans and Neandertals failed to show evidence of mtDNA exchange. Thus, Pääbo and colleagues conclude, while it's possible that Neandertals made a small contribution to the genetic makeup of contemporary humans, the evidence cannot support the possibility of a large contribution.

Copyright: © 2004 Public Library of Science.

The actual article can be downladed (as a PDF) by CLICKING HERE.

[lagarvelho]

Jacques and all:

The data rely heavily on mtDNA(more correctly, *only* on mtDNA), as far as I can tell; I'll have to read the article with some care, and I just got it), but the problem with all these ways of approaching such matters is, they don't tell us anything about what populations actually did(IOW, it tells you about lineage history, but not population history).  That's just my opinion, of course, based on what I've read so far. And I doubt that it's going to stop debate at all.  At least not in the near future.  
Anne G

[Jacques Cinq-Mars]

All,

Here is what Nature Science Update has to say about the Serre & al. PloS paper. The most interesting (cautionary) comments are from Serre himself. I have put them in "red" in the text.

Early man steered clear of Neanderthal romance. No evidence of interbreeding between primitive humans.

MICHAEL HOPKIN

Nature Science Update -- Wednesday, march 17.

If our early ancestors did breed with their Neanderthal cousins, they didn't make a habit of it, according to the largest-ever study of early human DNA.

Researchers compared the preserved remains of four Neanderthals and five early modern humans found throughout Western Europe. DNA from the two sets of samples was distinct enough to rule out large amounts of mixing between the two.

"We detected no evidence of interbreeding," says David Serre of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, who took part in the study. But he adds that, because of the scarcity of well-preserved DNA, it is impossible to be certain that such trysts never took place.

Neanderthals vanished from Europe between 30,000 and 40,000 years ago, roughly the time that truly modern man made his first appearance in the region. Researchers have been divided over whether the two groups ever came face to face - and if they did, whether relations were hostile or harmonious.

Family ties

Serre and his colleagues set out to shed light on this question by examining sequences of mitochondrial DNA taken from fossils. These sequences are passed virtually intact from mother to offspring - if Neanderthals and modern humans interbred, the sequences would be expected to overlap between the two groups. But the sequences were entirely distinct, the researchers report in PLoS Biology1.

"It's an advance," says Chris Stringer, who studies early humans at Britain's Natural History Museum in London. The finding supports the theory that our earliest European ancestors replaced Neanderthals, rather than mixing to form a single group that eventually gave rise to the people of today, he says.

But it's not yet fully clear how this process unfolded: did modern humans bully their slow-witted neighbours to extinction, or did the Neanderthals die out and leave us to inherit an empty landscape?

"I don't think DNA can answer this question," says Serre. Although the two groups seem to have been genetically separate, the fossil record is too patchy, and dating methods too unreliable, to say whether this was because they never met, or because they simply didn't consider each other an enticing proposition.

Given the small number of fossils studied, it's also possible that interbreeding did occur, he adds, but that we have not found the evidence yet.

Such a match-up would have been genetically feasible, says Stringer. The two groups were closer in genetic terms than other primates that happily breed today, he says.

Physically, however, they were very distinct, he adds. Perhaps the Neanderthals' thickset build and furrowed brow were just too different for romance to blossom.

So what did happen to the Neanderthals? Stringer points out that Europe's climate was very unstable at around the time of their demise. This, combined with the arrival of a cunning new competitor in modern man, could have conspired to wipe them out. "If the climate had been stable, perhaps the two could have overlapped for some time," Stringer speculates. "In my view, the Neanderthals were just unlucky."
References

   1. Serre, D. et al. PLoS Biology, published online, doi:10.1371/journal.pbio.0020057 (2004).|Article|


© Nature News Service / Macmillan Magazines Ltd 2003

From the above statements, it is clear, I think, that Serre is a bit more cautious and scientifically realistic than Stringer in his appraisal of the significance of the results of this study.

Jacques Cinq-Mars

[Daryl Habel]

From Serre et al. (2004) "Concluding Remarks":

"It is noteworthy that under the model of constant population size, about 50 early modern human remains would need to be studied to exclude a Neandertal mtDNA contribution of 10%. To exclude a 5% contribution, one would need to study more early modern human remains than have been discovered to date. Thus, definitive knowledge of the extent of a putative contribution of Neandertals to the modern human gene pool will not be possible, although extensive studies of variation in the current human gene pool may clarify this question (Wall 2000)."

All this is assuming they can eliminate contamination problems, and that the HVR I is not susceptable to selection, and that their analysis has been performed perfectly, and so on, etc..  Even if all that is true,  I think a careful reading of the paper shows that, to paraphrase the the media-headlining, "no Neanderthal contribution detected", could easily be slanted in another direction to "Neanderthal contribution cannot be excluded", even if their results conclude the contribution was no more than 25% and probably was less.

Freely admitting my bias toward reading mtDNA analyses with saltshaker handy.

Dar

[colin]

Dar
Good to hear your contributions - your obviously in good form.
With regard to Serre, I think your right to keep the salt cellar handy. His line about AMH resisting romance with neanderthals I find unlikely simply on the grounds that - and  I dont want to lower the tone too much in a learned debate - AMH in modern times show a propensity to mate with inflatable dolls and goodness knows what, so the idea they were  so choosy  in the past I find unlikely.
Cheers
Colin

[Daryl Habel]

Dar
Good to hear your contributions - your obviously in good form.
With regard to Serre, I think your right to keep the salt cellar handy. His line about AMH resisting romance with neanderthals I find unlikely simply on the grounds that - and  I dont want to lower the tone too much in a learned debate - AMH in modern times show a propensity to mate with inflatable dolls and goodness knows what, so the idea they were  so choosy  in the past I find unlikely.
Cheers
Colin

Hi Colin,

With regards to being in "good form", admittedly I was up on my soapbox with concerns about contamination, selection, etc., but I do not wish to be overly critical of the Serre et al. analysis, other than to point out that it is a statistical conclusion in which various parameters used in the math are presumed true, when in fact these parameters are open to question.  I'm sure they took all precautions to eliminate contamination, and the math is done with the usual presumption of HVR I selective neutrality.  But others have questioned whether it is not possible that selection in other regions of the mtDNA genome might carry the HVR I sequences in "piggy-back" fashion, thus selection in one region affects selection in all regions of mtDNA.  Also, the authors freely admit that, "in the absence of further technical improvements, it is impossible to produce indisputable human mtDNA sequences from ancient remains" (p. 0314), yet the math which they use in the analysis clearly includes both the 24,000-year-old AMH sequences as well as the additional fragmentary AMH sequences described in their paper.

Other than pointing to questions I have about the parameters, I don't have any particular objections to the Serre et al. analysis.  I'd even go so far as to agree with them that by using a more "realistic" model of population growth, the Neanderthal contribution would be less than 25%.

Still, a 10-25% contribution does not seem unreasonable, when considering that mtDNA only tells the female half of the story from one locus in the human genome.  And I think a good many advocates of all but the most strict MREH would go along with this as at least a reasonable possibility under some models of prehistoric demographics.  My biggest gripe comes from the fact that these studies always seem to be accompanied by sensationalistic headlines, such as that in the Nature Science Update article, "Early Man Steered Clear of Neanderthal Romance," and the like, which place the emphasis on no interbreeding detected, with added implications that none took place.

So I don't think you can blame Serre for that particular headline, which more properly can be assigned to the editorial staff of Nature Science Update.  I would just like to see a bit more even-handedness in the journalistic reporting of these mtDNA studies presented to the uninitiated public, largely ignorant of the realites involved.

Dar
[climbing down from soapbox]

[lagarvelho]

All:

I think it's important to keep Colin's remark about "inflatable dolls" in mind here when people --- scientists or not --- get up on their soapboxes and make claims about early human mating habits.  Yes, the genomes of the two groups apparently (in some ways) different.  But did this affect ideas about mating?  I don't know.  On the one side, you have people like Paabo claiming litte or no contribution to "modern" humans, and on the other, you have people like Trinkaus and Zilhao claiming that there probably was.  Anomalies on either side can be explained away by the promoters of either view.  And as someone (Dar?) suggested, it would apparently take extractions of DNA from more early "modern" fossils than apparently exist tod date, to prove or disprove either set of claims.  Neandertal DNA apparenlty won't work, because it's so incomplete.  And so the debate goes on.  And on.  And on.
Anne G

[Daryl Habel]

For the uninitiated, or the curious initiated, here is more fallout on the debate.

From an old 2003 issue of Science News:

CLICK HERE

The 2003 Science News article, announcing results reported in Caramelli et al. (2003) has a number of interesting quotes from various scientists, as well as a number of links to more information.  As well as the contamination problems, the matter of selection was brought up by Milford Wolpoff in an earlier Science News article (one of the links from the 2003 article).

CLICK HERE FOR WOLPOFF'S QUOTE

Bruce Bower is more even-handed than some reporters.  For instance, Richard Klein, who naturally is overjoyed by this new Serre et al. (2004) analysis, is quoted extensively in the current Discovery.com article "Study: Humans and Neanderthals Did Not Mate", at:

CLICK HERE

But no one from the opposing camp is quoted.

Anyway....the beat goes on (and on).

Dar

[Dale Hoogeveen]

It is interesting to note that this article does some work on probability of participation at various levels of interaction and at various levels of relevant populations, coming up with different results for each.  IIRC there has been some other work about the effects of subsequent mushrooming populations.  Sarich quoted some of that about ten years ago.

What I have not seen is what effect a possible randomized reduction in female reproductive participation growing out of concealed ovulation might have on the ability of human populations to maintain mtDNA variation.

Should that result in extremely short average numbers of generations in mother daughter strings, I would think that humans would first display a very high extinction rate on the shortest lineage branches, tending to reduce ongoing mtDNA lineages to minimal numbers, and second concentrate mtDNA expression in those ongoing lineages.  

There must always be at least one, since every daughter must have a mother, but how many more must there be, especially in extremely low density populations?  Perhaps even better one should ask how few are there going to be?  It seems to me that low density human groups may very well have worked on very close to a one surviving lineage level amoung women in particular breeding pools.

And when different populations interact, even with complete reproductive freedom, would not there be the probability that one will be reduced or lost as the  automatic result of reduction in ongoing strains to minimum ongoing quantities, especially at the extremely small population levels that would have been typical of any Neanderthal (or other local archaic human group) interaction with any "modern" group.  

FWIW it seems to me that those levels would more than anything actually tend to interact in series of 10 to 15 individuals that in a single group comprising thousands, which it seems to me very much increases the likelihood that Neanderthal genetic contribution to ongoing populations would have been transparent to ongoing mtDNA lineages.  There would have been no outside support to replace Neanderthal losses.  It seems to me that Neanderthal mtDNA should have disappeared regardless of anything else that happened.

What a single surviving main group of mtDNA lineages would seem to show more than anything is a hugely expanded territorial integration of human reproduction, not extensive exclusion.

Dutch

[trehinp]

Dear All,

Thanks for all this excellent discussion/information. I have a question concerning this topic. Bear with me, I am very naive on this subject, just interested.

Does any of you know if there have been hypothesis or theoretical model made on the fertility or lack of thereof in offsprings of potential interbreeding between Modern human beings and Neanderthals ?

Could it be a possibility that the reason why we find very little evidence of Neanderthal heritage in molecular genetics of modern man was that offsprings could have been sterile ?

Paul Trehin

[Daryl Habel]

Dear All,

Thanks for all this excellent discussion/information. I have a question concerning this topic. Bear with me, I am very naive on this subject, just interested.

Does any of you know if there have been hypothesis or theoretical model made on the fertility or lack of thereof in offsprings of potential interbreeding between Modern human beings and Neanderthals ?

Paul,

The answer to this hinges on resultion of the "species" problem, for which there is no present consensus.  Trinkaus and Zilhao have hypothesized ("modern"/Neanderthal) inter-fertility extending over several thousand years (more than 3,000 yrs) to explain the mosaic of traits in the 24,000 year old Lapedo child from Portugal; i.e., that this was not a one-time event.  It appears to me that they favor the single-species hypothesis, with subspecies populations.  Similar suggestions have also been made to explain the mosaic of archaic and modern traits seen in the anatomy of a good number of Central European Aurignacian and Gravettian period fossil humans.

However, those who advocate separate species (Hs & Hn), doubt this hypothesis, and (Tattersall & Schwartz, for instance) say the Lapedo child is instead a chunky Gravettian AMH.  The same separate species advocates do not consider the Central European fossils of Aurignacian/Gravettian age as possessing evidence strong enough to consider them anything but modern humans who have retained some archaic traits.

Until the "species" problem is resolved to a better consensus, all theoretical models/hypotheses of fertility or lack thereof would produce results consistent with the initial presumption(s) made of species status.

Could it be a possibility that the reason why we find very little evidence of Neanderthal heritage in molecular genetics of modern man was that offsprings could have been sterile ?

Paul Trehin

That is a possibility that has been put forward in the past by several "two-species" advocates, but, so far as I know, there is no way to determine whether or not such was the case.  As I said above, it all depends on resolution of the "species" problem.

There probably are better answers to these questions, but that's about all I can say, off the top of my head.

Dar  

[skwirl42]

Has there been any simulation work on the possibility of Neanderthal contributions to AMHs? I think a properly laid out simulation could answer how long it would take for mtDNA to be almost invisible, and even provide insights into the general question of how much genetic contribution a small population can make to a much larger one.

[lagarvelho]

skwirl:

I don't know about any simulations, but John Relethford has explained some of the mathematical models that(to him)suggest there weren't that many Neandertals around to make a contribution in the first place, and therefore, any contribution would have been sort of like putting a pint or white paint into a gallon of red, and adding the red to more red paint.  You can read this(if you're interested) in his "Reflections on our Past", which came out last year.
Anne G

[skwirl42]

Anne:

It definitely does interest me. I'll take a look at that as soon as I get the chance. Given my computer science background, simulation is likely to be a big component of any research I do, and any simulation requires some sort of model. :)

[lagarvelho]

skwirl42:

I think you might find that book useful.  There are others that I know of, written for laypeople and which explain things fairly clearly so that even  *I* can understand what they're getting at.  If you're still interested, I can recommend some other books, though not very many, unfortunately.
Anne G