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Randy Neanderthals?

Posted 8 November 2006 by Andrea Bottaro

In population genetics, the influx of new genetic variants from one population to another after a period of genetic isolation is called introgression. One of the most intriguing questions in anthropology is the possibility and role of introgression along the Homo sapiens lineage, that is, in more mundane terms, the extent to to which our H. sapiens ancestors were willing and able to mate with other coexisting human species (such as H. neanderthalis, and possibly even H. erectus), and whether such exchange of genetic material played any role in our evolution. Molecular evidence from available Neanderthal mitochondrial DNA, which is transmitted to the progeny by females alone, has suggested that Neanderthal gals did not contribute to H. sapiens's current mitochondrial genetic diversity. Whether any trace of sapiens-Neanderthal interbreeding can be detected in nuclear genes, however, is still an open question. A paper appearing online yesterday in PNAS (free access, for once!) reports strong evidence of introgression for a variant of the microcephalin gene, known to be involved in brain development and size. To make a very long story short, it appears that a common human variant of the microcephalin gene originated on a chromosomal region that separated from the human lineage over 1 million years ago, only to come back ("introgress") into H. sapiens about 37,000 years ago. John Hawks's Anthropology blog has a couple posts with an excellent explanation of the story, so I'll just send you there to read about it. John also hints at more evidence coming out in the near future for sapiens-Neanderthal hanky-panky, and of course Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, the whiz of ancient DNA analysis, has recently announced his goal to clone and sequence the Neanderthal genome, which is likely to yield more information in this regard, so stay tuned...

12 Comments

Coin · 8 November 2006

Dumb question. Let's say we could sequence the genome of something extinct, like a neanderthal or a mammoth. How much would science have to progress before we could use that sequenced genome to clone a living organism?

Clastito · 8 November 2006

From what I quickly read at Hawk's, it does not sound sooo convincing to me... for now let's be kind and grant that no one has screwed up in the time calibrations of sequence differences (of course!).
Genes older than the split of all modern humans may have remained in the genetic diversity of the lineage leading to modern humans, without it implying introgression. Are there no biological explanations to why a gene may fail to recombine other than that it has been in an isolated lineage?
If more versions of these genes are being found where there were no neanderthals, are we going to accept this or not as a way of putting to test the alleged mixture from neandertals that gave europeans these allegedly super advantageous brain genes?
Indeed, what are we accepting as evidence that may refute the whole thing? The fact that NO genetic evidence for human-neandertal hybridization may ever turn up does not seem to worry Hawks too much. Nor does the fact that all recovered neandertal genes are veeeeery different, unrepresented in human populations.

Can sequence comparisons of microcephalin alone be trusted as evidence of such two major biological events as: 1) mixture with the neandertals 2) selective advatages for humans with the D microcephalin gene, despite the fact that what these advantages would be reamains totally murky, since people without that gene do fine.

Please allow me to remind the alternative: Other, less spectacular explanations may exist for these sequence comparisons...specially if combined with drift. Can drift be confidently discarded? I mean, what a coincidence... that the D version is only common in populations that came out of africa... hmmm
Can we lay all our trust into the comparisons of the microcephain gene for all this without confirmation from nenadertal genes nor any other reliable independent source of data? Sorry, that's way too much for my level of skepticism. Artifact, alternative explanation suspected.
I would sincerely appreciate a more explicit statement on what evidence could effectively DISCARD this hypothesis.

JoshuaK · 8 November 2006

One slightly irreverent question comes to mind - did the Rev Haggards of the day consider it to be sodomy or merely miscegenation? :)

Slightly (but only slightly) more serious - H. sapiens is willing and able to mate with the entire subphylum, let alone the genus. Perhaps "breed" would be a better word.

David B. Benson · 8 November 2006

As I recall the matter, there is a distinctive feature of the jawbone shared only by (some) Europeans and Neanderthal.

djlactin · 8 November 2006

This proposition of genetic introgression from Neandertals resonated with me a bit. You may recall, a few weeks ago Nick Matzke posted a chart of changing hominin brain volume vs. time. We played with it a bit and were able to estimate slopes of the lines for each "species" in mL/million years. I summarize:

A. afarensis 434
A. africanus 31
A. robustus -114
"A". habilis 98
A. boisei 102
H. erectus 158
Achaic H. s. 150
H. neander.. 1694
H. sapiens 351

The odd "man" out? Neandertals, with a brain growth rate that requires a new scaling of the y-axis! Neandertal brain expansion was 5 times greater than that of modern himans and more than 10 times greater than archaic Homo sapiens!

Obviously, this observation is not proof of the Neandertal brain-gene introgression hypothesis, but it is certainly consistent with it.

Torbjörn Larsson · 9 November 2006

Hawks starts at http://johnhawks.net/weblog/reviews/early_modern/europe/pestera_muierii_2006.html .

Clastito (And may you be Alexander Vargas, perchance?):

You posted an identical comment at Pharyngula. While we wait for the experts:

The extensive anatomical and genetic evidence Hawks cites makes the case for introgression, and Neanderthal specifically, easy to accept I think.

"Are there no biological explanations to why a gene may fail to recombine other than that it has been in an isolated lineage?"

I'm not a biologist, but didn't the paper (and Hawks) discuss this? They mention "balancing selection", whatever that is, as an alternate explanation "for maintaining the coexistence of D and non-D alleles". In other cases this can't be discarded (though Hawks seems to disagree) but here it can be shown to be highly unlikely due to the lack of the main mechanism for suppressed recombination. ( p 4.)

"Can drift be confidently discarded?"

Again, outside my domain by far, but the paper seems to say so. They use this as the null hypothesis. (p 4.) "simulations of ancient admixture showed that an archaic genetic contribution <0.1% is unlikely to be detectable" (p 1.)

Hawks discusses a lot of alternative hypotheses. His conclusion: "Complete replacement is completely out. "Mostly" replacement, or "assimilation" is still in, but with the observation that archaic human genes had substantial evolutionary importance in the adaptation of modern humans.

In other words, we have moved the ball down the field. Time to line up for the next play."

David:
I think Hawks goes through some such features at the link above. He claims that "this broad and altering mix of features in different specimens" argues against parallelism or retaining of features.

Andrea Bottaro · 9 November 2006

That is correct - drift is already considered as part of the model, and of course there are alternative possibilities, although they seem at this point less likely than introgression. E.g., it could be that the microcephalin D variant arose in the sapiens lineage, but on a unique chromosome version that was both much more rare and significantly older than all other existing chromosome versions, and then the parental chromosomal variant, after persisting for so long, went completely extinct while the D variant spread out. It is possible in principle, but very unlikely. I strongly encourage people to read the original paper, which is exceptionally well written and I think very accessible to the layperson.

Coin: Let's say we could sequence the genome of something extinct, like a neanderthal or a mammoth. How much would science have to progress before we could use that sequenced genome to clone a living organism?

In short, a LOT. It's hard but not impossible to clone all the DNA, but this is done in fragments that are then expanded in bacteria and sequenced independently. Therefore, even with all the DNA available one would need to a) putting all the fragments back together in the right order to reconstitute the original chromosomes, b) transfer that chromosomal DNA into the nucleus of a cell whose chromosomes have been selectively ablated somehow, c) ensure that all the highly complex protein-DNA interactions that are associated with normal chromosomal DNA inside the cell nucleus and are involved in gene expression regulation etc, are re-created, and d) get a living organism from that cell. Of these steps, only d) seems feasible at this point. (Incidentally, when people talk about cloning a mammouth, they are actually suggesting something that would entirely skip steps a-c, i.e. finding an intact enough somatic frozen cell from a frozen mammouth, extracting the nucleus from that cell, injecting it into an enucleated elephant oocyte and activating the product to divide and develop into a baby mammouth after transferring it into an elephant foster mother uterus. Apart from the ancient frozen cell part, this is akin to the cloning process that people have used to generate cloned cows, cats, dogs, etc.)

JoshuaK: Slightly (but only slightly) more serious - H. sapiens is willing and able to mate with the entire subphylum, let alone the genus. Perhaps "breed" would be a better word.

Of course. ;-)

Clastito · 10 November 2006

I am not talking of drift over the point of whether microcephalin D is the result of ingression, but on the claim that its increased frequency in non-african populations really is the result of selection. 
But about the alleged ingression, I insist: calibrations of the dates of divergence of genes is no small issue...
For instance, I heard a lot of speculation about the supposed difference in the time of divergence of all Y chromosomes, which was more recent than that of mithochondrial genes. After reading many crazy hypotheses about how Y chormosomes spread to ALL of humanity by selection, cultural means, etc. I found one small comment in a Cavalli-Sforza paper in nature... that it was an interesting possibility that the discordance in the dates of them may come from an artifact in callibration and estimation of their divergence.
So, hypotheses of technical artifacts just do not get as much attention as more fantastic explicative scenarios.
I do not deny the possibility of introgression, I think it is an interesting and somewhat overlooked source of evolutionary innovation. But, I believe it is normal scientific procedure to figure as many independent sources of data that may prove consistent with such colorful hypotheses, rather than rely entirely on estimates derived from computer simulations for what is likely and what is not (failure to model reality always lurks).
For instance, evidence that birds are dinosaurs has been available for many years, but the best thing about that story is how succesive challenges have been met by evidence confirming over and over agains its airtight consistency, in the face of decades of persitent opposition. 
That's why, while knowing I may be wrong, I consider I do good in demanding evidence of the D microcephalin ( or simply just ANY human gene) in a neanderthal, I demand a clear effect and selective advantage between someone that has the D and someone that does not (just "assuming" an almost invisible slight fine tuning does not work). I truly worry when rather than strain for different sources of confirmation, some ALREADY settle into saying "this may be as good as the evidence will ever get". If that is indeed true, this means to me that the whole idea is condemned to the hypothetical realm and may never cross the line into fact. 
Stay alert: More inconsistencies in divergence dates for genes may show up, such that we may have to postulate more and more introgressions, with other ape-men lineages: I know this was already proposed for admixture with chimpanzee ancestors...once we have all possible introgressions, we may not always find actual availability of apemen, in time and space, to provide the "archaic" genes. And then what?

Clastito · 10 November 2006

I am not talking of drift over the point of whether microcephalin D is the result of ingression, but on the claim that its increased frequency in non-african populations really is the result of selection. 
But about the alleged ingression, I insist: calibrations of the dates of divergence of genes is no small issue...
For instance, I heard a lot of speculation about the supposed difference in the time of divergence of all Y chromosomes, which was more recent than that of mithochondrial genes. After reading many crazy hypotheses about how Y chormosomes spread to ALL of humanity by selection, cultural means, etc. I found one small comment in a Cavalli-Sforza paper in nature... that it was an interesting possibility that the discordance in the dates of them may come from an artifact in callibration and estimation of their divergence.
So, hypotheses of technical artifacts just do not get as much attention as more fantastic explicative scenarios.
I do not deny the possibility of introgression, I think it is an interesting and somewhat overlooked source of evolutionary innovation. But, I believe it is normal scientific procedure to figure as many independent sources of data that may prove consistent with such colorful hypotheses, rather than rely entirely on estimates derived from computer simulations for what is likely and what is not (failure to model reality always lurks).
For instance, evidence that birds are dinosaurs has been available for many years, but the best thing about that story is how succesive challenges have been met by evidence confirming over and over agains its airtight consistency, in the face of decades of persitent opposition. 
That's why, while knowing I may be wrong, I consider I do good in demanding evidence of the D microcephalin ( or simply just ANY human gene) in a neanderthal, I demand a clear effect and selective advantage between someone that has the D and someone that does not (just "assuming" an almost invisible slight fine tuning does not work). I truly worry when rather than strain for different sources of confirmation, some ALREADY settle into saying "this may be as good as the evidence will ever get". If that is indeed true, this means to me that the whole idea is condemned to the hypothetical realm and may never cross the line into fact. 
Stay alert: More inconsistencies in divergence dates for genes may show up, such that we may have to postulate more and more introgressions, with other ape-men lineages: I know this was already proposed for admixture with chimpanzee ancestors...once we have all possible introgressions, we may not always find actual availability of apemen, in time and space, to provide the "archaic" genes. And then what?

Clastito · 10 November 2006

I am not talking of drift over the point of whether microcephalin D is the result of ingression, but on the claim that its increased frequency in non-african populations really is the result of selection. 
But about the alleged ingression, I insist: calibrations of the dates of divergence of genes is no small issue...
For instance, I heard a lot of speculation about the supposed difference in the time of divergence of all Y chromosomes, which was more recent than that of mithochondrial genes. After reading many crazy hypotheses about how Y chormosomes spread to ALL of humanity by selection, cultural means, etc. I found one small comment in a Cavalli-Sforza paper in nature... that it was an interesting possibility that the discordance in the dates of them may come from an artifact in callibration and estimation of their divergence.
So, hypotheses of technical artifacts just do not get as much attention as more fantastic explicative scenarios.
I do not deny the possibility of introgression, I think it is an interesting and somewhat overlooked source of evolutionary innovation. But, I believe it is normal scientific procedure to figure as many independent sources of data that may prove consistent with such colorful hypotheses, rather than rely entirely on estimates derived from computer simulations for judging what is likely and what is not (failure to model reality always lurks).
For instance, evidence that birds are dinosaurs has been available for many years, but the best thing about that story is how succesive challenges have been met by evidence confirming over and over agains its airtight consistency, in the face of decades of persitent opposition. 
That's why, while knowing I may be wrong, I consider I do good in demanding evidence of the D microcephalin ( or simply just ANY human gene) in a neanderthal, I demand a clear effect and selective advantage between someone that has the D and someone that does not (just "assuming" an almost invisible slight fine tuning does not work). I truly worry when rather than strain for different sources of confirmation, some ALREADY settle into saying "this may be as good as the evidence will ever get". If that is indeed true, this means to me that the whole idea is condemned to the hypothetical realm and may never cross the line into fact. 


Richard Simons · 11 November 2006

Years ago, when I lived in Wales, I was told (by a scientist) that a group of people living in the hills had several traits that were common in Neanderthals. Until the 1930s this area had been remote and the people kept very much to themselves. The last survivors of 'Plynlimon Man' died around 1970 but there are local people who claim descent from them. I realize it is unlikely that they actually were descendents of Neanderthalers but I've always wondered if anything had been done with these people. Does anyone here know?

Torbjörn Larsson · 17 November 2006

Clastito:
Sorry for late answer, life imposed.

"But about the alleged ingression, I insist: calibrations of the dates of divergence of genes is no small issue..."

Again, the paper deals with this.

"I believe it is normal scientific procedure to figure as many independent sources of data that may prove consistent with such colorful hypotheses"

Again, Hawks deals with this.

Go read them.