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Sunday, May 9, 2010

On some details of the Neanderthal genome draft


Still chewing on the Neanderthal genome draft (
Green 2010). Only today I have got some time to dwell on some of its details.


Alleles specific to all Homo sapiens (and not to Neanderthals)

It's interesting not just that some of us carry a small apportion of Neanderthal alleles but also the list of alleles that are exclusive of our species. Green et al. dwell on this matter in the section titled A catalog of features unique to the human genome.

There is a list of 78 alleles (table 2) that are fixated in the derived (non-Chimpanzee) form in the species Homo sapiens exclusively and found in their ancestral state among Neanderthals. Many are not really known their role but others seem to accumulate in certain processes such as skin (sweat...), melanin, smell, vision, sperm motility, hormonal and cellular division regulatory processes. This suggests me that there were some marked biological and appearence differences among the two species in spite of the proximity.

Therefore the inter-species barrier was possibly rather high even if still not total.

The authors emphasize specially five alleles in which more than one SNP is different, suggesting greater differences. These are specially related to skin morphology and regulatory substitutions (specificity).

Also the studied certain regions in clear rapid evolutionary change in the line leading to humans called HARs. The vast majority of these HARs had already evolved before the Neanderthal-Sapiens transition but a few (c. 1.7%) had not yet and belong specifically to Homo sapiens.

These human-specific HARs include genes related to mental functions (associated with mental disorders such as Dow syndrome, schizophrenia and autism) as well as a the RUNX2 (CBFA1) gene that would be related to changes in skull, clavicle and ribcage morphology.


Are Chinese slightly 'more Neanderthal' than other Eurasians?

Less definitely, when working with the comparative data at table 4, I find that the Han Chinese sample (n=2) appears very slightly but maybe significantly "more Neanderthal" than the other Eurasians, including the only Japanese. The Chinese individuals differ from the African sample in Neanderthal alleles by an average factor of 5.05 (4.95 and 5.15), while the non-Han Eurasian average is 4.21 (3.93-4.65), that is: almost a point more. Only one European individual (4.65) really approaches the Han Chinese figures, which differ by almost a whole point (0.92) from the rest.


This, of course, can only be a very preliminary indication but it does seem intriguing and potentially meaningful. The fact that the greatest difference is with the, otherwise very close, Japanese could even point to some greater diversity patterns in East Eurasia in regard to Neanderthal genes in us, and, considering the tiny sample sizes, even in much of the rest of Eurasia.

28 comments:

Kepler said...

I always thought, specially when talking to some guys from Eurasia: Oh, my God, homo sapiens must have interbred with Neardenthals.

Look at this famous Flemish socialist:
Johan Vande Lanotte

:-p

No, seriously: these are interesting days, there is a lot we may find out about in the coming months.

I wonder if one day we will find a better preserved Neardenthal in the receding glaciers of Switzerland...as far as I understand, these guys are working with pretty damaged material and they have "reconstructed" DNA sequences by using software that is simply remapping sequences that are deemed to be corrupted.

Maju said...

Interesting day indeed.

I must say that, as far as I can tell, the Paabo team are using the most refined methods so far in aDNA processing and double-checking. There's always something better in the future, you know, but by today's standards their methods are "la creme de la creme".

However it is true that the vast majority of the DNA recovered was of microbial organisms and had to resort to some special amplification methods. But the results seem pretty good anyhow. They checked for possible Eurasian->Neanderthal contamination by using known genetic distances to Yoruba (closer) and San (more distant) and the result does not correspond with any such possible contamination.

It seems as good as it can be.

Another thing is interpreting the results, there's where the core of the discussion is, IMO.

And, as Lalueza Fox says, the extended comparison with a much broader human full genome sample will be most interesting to follow.

:)

Ken said...

"It was another surprise that even the Chinese carry Neanderthal genes, although Neanderthals never lived in China,"

Shouldn't Chinese have far less Neanderthal genes than Europeans if the Neanderthal genes entered the European gene pool in Europe?

Maju said...

You haven't read the paper, right Ken?

You have not read what this blog has said in this regard (for example here).

What Green and colleagues have found is that there is a small amount (1-4% estimated) of Neanderthal-specific genes that are present among non-Africans (European, Chinese, Japanese and Papuans in similar apportions, as illustrated by my graph) and not among Africans (Yoruba and San).

The fact that, overall, Eurasians are much closer to Yoruba than to Bushmen served as control. Because both Bushmen and Yoruba are similarly non-Neanderthal. But Eurasians are all and at very similar apportions (I was here just exploring the minor differences in that Eurasian quite homogeneous Neanderthality - wow, I just invented a new word!)

terryt said...

"The Chinese individuals differ from the African sample in Neanderthal alleles by an average factor of 5.05 (4.95 and 5.15), while the non-Han Eurasian average is 4.21 (3.93-4.65), that is: almost a point more. Only one European individual (4.65) really approaches the Han Chinese figures, which differ by almost a whole point (0.92) from the rest".

I think it would be extremely unlikely that any two individuals would have exactly the same number of Neanderthal alleles (unless they happened to be advantageous), no matter how early the mixture had occurred. Therefore we should expect to see a varying amount of Neanderthality in each modern individual.

Maju said...

Sure, Terry. I'm extremely cautious: just suggesting a possible structure maybe hinted by the small sample. I though I saw a pattern but you know that our minds are programmed to look for them.

Ken said...

Sorry Maju I am clueless about this stuff, thanks for taking the time to explain.


"Therefore the inter-species barrier was possibly rather high even if still not total".

Maybe it was total, the Neanderthal alleles in modern humans could have other explanations such as modern humans mating with a not-fully-human population which had hybridized with Neanderthals.

Hybridization with humans would have given the European Neanderthals the basis for rapid evolution so why didn't they show
any evidence of that?

Maju said...

"Maybe it was total"...

We know of too many inter-species barriers that are not total. Even with the archaeological count of almost 1 million years divergence, we'd be quite close comparing with some species over there that are inter-fertile but much more distant.

"... the Neanderthal alleles in modern humans could have other explanations such as modern humans mating with a not-fully-human population which had hybridized with Neanderthals".

Not sure what you mean by "not-fully-human": Neanderthals are the closest Homo species re. us with all likelihood. Also the Africa/Eurasia differential is so clear and sharp that I can't really think of any other possible explanation that is not simply absurd.

It's quite possible that the genetic flow happened within rather small populations of both H. sapiens and Neanderthals, which became more genuinely hybrid at least on occasion. Then the some of these hybrids, maybe at 25% or 12% were assimilated by a pure H. sapiens population. The parallel Neanderthal hybrid population would never really back-migrate to Europe, what explains the lack of Sapiens genes among Neanderthals.

But this is just one of many possible histories.

"Hybridization with humans would have given the European Neanderthals the basis for rapid evolution so why didn't they show any evidence of that?"

I think you are imagining that somehow Sapiens genes were more adaptative. But, sincerely, unless proven otherwise I take genes as "mostly neutral". And while in the long run H. sapiens happened to be a more adaptative species this may have got only so much to do with genes, or even be such a remote and untestable result that we can disregard the genetic element almost totally and consider it a socio-economical one.

Would we inherit Neanderthal genes that make our legs shorter, we'd be less adaptative in a Sapiens context, but would a mixed Neanderthal be born with slimmer body, he/she would be less adaptative in a Neanderthal context (the "neutral" genes are adaptative/harmful depending on circumstances and not so much on what they do - context is all). So the genes that remained transfered are not about such specific stuff, quite clearly, but other random ones.

Eventually we'll know with more detail.

Andrew Oh-Willeke said...

The fact that Papuan and Japanese are on the opposite side of European from Chinese suggests slight variations in percentages exacerbated by founder effects, rather than any more profound population structure.

Ken said...

Maybe I'm not so clueless after all! Direction of gene flow (to or from Neanderthals, or …?)

Maju said...

That's a copy of the latest post by Dienekes on the issue. Not sure if he knows.

I'm already discussing this issue with him at his blog. You may want to read the comments.

Ken said...

Yes! I am clueless after all

Ken said...

Neanderthals who were not raised by humans would be terrified of humans, like a bonobo would be terrified of a chimp in the wild.

No human could have mated with a 'wild' Neanderthal, they'd get parts of their anatomy bitten and twisted off.


It could be that infant Neanderthals were sometimes kept as a pets after their parents were hunted and occasionaly stayed alive long enough to mate with humans - < 10 years, they matured fast - and that the mating of a non-pet Neanderthal with a human never took place. That would explain why the genes flowed one way; the offspring all were born into a band of humans.

If the humans who shared Europe with Neanderthals have died out and been totally replaced since that would explain why Europeans don't have any extra Neanderthal ancestry.

Maju said...

"Neanderthals who were not raised by humans would be terrified of humans, like a bonobo would be terrified of a chimp in the wild".

They were much stronger, remember? If anything H. sapiens would be the scared ones.

"No human could have mated with a 'wild' Neanderthal, they'd get parts of their anatomy bitten and twisted off".

That's just a fantastic speculation of you. Neanderthals were surely as tender and overtly 'human' as we are or nearly so.

"It could be that infant Neanderthals were sometimes kept as a pets after their parents were hunted and occasionaly stayed alive long enough to mate with humans"...

Adoption is certainly a possibility in this story but I would not consider such close conspecifics as "pets": they were smarter than you in many cases probably. Remember that they had really big brains, larger than the modern average.

They were not just "all brawn, no brain" but more the Schwarzenager type: strong but intelligent enough to be governor. Of course, there must have been quite a lot of diversity but that was surely the trend.

"If the humans who shared Europe with Neanderthals have died out and been totally replaced since that would explain why Europeans don't have any extra Neanderthal ancestry".

It is not necessary (nor really likely, IMO). I'd dare say that in that late period, if there was any genetic flow, it was from Sapiens to Neanderthals (some of which look "sapienized"), probably because then our species already had the upper hand.

Kepler said...

As I said initially: the reconstructions of Neardenthals I have seen even in the museums in Germany seem very human to me.

I am just reading a biography of Caesar (Adrian Goldsworthy, very good). They described the battles time after time and one thing was obvious: massive rape took place. Could this not have happened?
Or just "blonde girl falls in love with big muscled and endearing guy" story?

Anyway: how many Neardenthals do we have? Not many, I would say. We know so little about their real distribution, just that the last ones were living in the Iberic Peninsula.

Considering what we know of comparative linguistics now, I think the next step is obvious: examine the Basque genome more closely
Just kidding (running for cover)

Maju said...

"the reconstructions of Neardenthals I have seen even in the museums in Germany seem very human to me".

They are reconstructions only: creative exercises. The real thing are the bones and they look somewhat less 'human' than the reconstructions.

"I am just reading a biography of Caesar (Adrian Goldsworthy, very good). They described the battles time after time and one thing was obvious: massive rape took place. Could this not have happened?"

Iron Age is much more similar to our reality than to Paleolithic. As the myth goes, bronze and iron ages are ages of chaos and violence... but there was a golden age first of all (Paleolithic?)

If you know anything about hunter-gatherers, they are not into such things. It's not impossible of course but not documented, much less between different communities.

Rape and such arise mostly where sex has been regulated, which can't happen among de-facto anarchist hunter-gatherers (though serial monogamy is the tendency). Doesn't really look like a good explanation, specially as most sex happens within ethnic communities (tribe or similar).

Let's see: the usual HG band of 20-35 individuals, which is just a communist operative unit, totally flexible as any member may leave at any time, is part of a larger 'clan' or 'tribe' typically above the 100 members, who gather for some seasonal celebrations and joint efforts. These clans may belong to a larger ethnic grouping or 'tribe'. Outside there may be people but are strangers (if they are considered to be human at all). Most sex happens between consensual couples within this ethnic group. However adoption and such happen too (incl. adoption of friendly adults).

So, if this event happened in the Levant, for example, it's likely that the surely distinct ethnicities of 'Palestinian' H. sapiens and 'Syrian' Neanderthals had amicable relationships for a long time, what allowed for some mixed couples, with some gene flow into both populations. If the event happened in Iran it'd be the same.

"Or just "blonde girl falls in love with big muscled and endearing guy" story?"

That's a good one (though no blonds yet probably). Heavily built Neanderthal women were surely not attractive for human males but that same constitution among Neanderthal males might have been quite interesting for women, I guess. That might also explain why the flow has only been detected among our species, because children would be reared within the mother's group (matrilocality).

"I think the next step is obvious: examine the Basque genome more closely"...

LOL. If French are not particularly affected, I doubt Basque are.

But the distant B006 X-DNA lineage is most frequent among some Europeans, notably Basques, and Amerindians as well (though it had highest diversity in Mongolia). It might be a case of Neanderthal lineage or maybe just a distinct 'Palestinian' human one.

terryt said...

"If you know anything about hunter-gatherers, they are not into such things".

I remember reading (years ago) that in Australian Aborigine societies it was common for women who had wandered too far away from their own tribal region to be raped. Not sure if it's still claimed to have been so. Also not claiming at all that it's the explanation here.

"it's likely that the surely distinct ethnicities of 'Palestinian' H. sapiens and 'Syrian' Neanderthals had amicable relationships for a long time, what allowed for some mixed couples, with some gene flow into both populations. If the event happened in Iran it'd be the same".

Agreed. And, as you are aware, it's a position I have long maintained.

"Heavily built Neanderthal women were surely not attractive for human males"

I know several men who are very much attracted to 'Heavily built ... women', so I wouldn't dismiss the possibility.

"That might also explain why the flow has only been detected among our species, because children would be reared within the mother's group (matrilocality)".

Someone pointed out at another blog that the Neandethals chosen for the study were from a pre-modern period. They made the comment that if post-contact Neanderthals had been examined we may find that gene flow had moved in that direction too, which makes sense to me.

Maju said...

"Someone pointed out at another blog that the Neandethals chosen for the study were from a pre-modern period".

Pre-modern for sure. There are no Neanderthals since the Early Upper Paleolithic. LOL

Again, have you read the paper? It's freely available!

Two of the specimens are dated (38 Ka and 44 Ka BP), while the third is older than the other two because of stratigraphic logic (say 60-70 Ka maybe).

All individuals used in the Neanderthal Genome project are of a rather late date, surely none older than 70 Ka ago. The most recent date is 38 Ka BP (roughly 43 Ka calibrated), which it's prior to Sapiens full colonization of Europe but surely after some good deal or colonization in West Asia and Central Europe had already happened.

So some of those bones are from the after-contact period most likely.

From this study:

- Vi33.16 (Vi80): 38 Ka BP = 43 Ka cal
- Vi33.26: 44 Ka BP = 47 Ka cal

The other individual is clearly older. But one of the other Neanderthals researched in the project is also from the post-Bohunician period:

- Neander Valley: 40 Ka BP = 45 Ka cal

The H. sapiens flow into West Eurasia, incl. parts of Europe, surely began 50-48 Ka ago (or maybe a bit earlier: 55 Ka ago), so these specimens are "post-contact" in the restricted sense you're using this term, because contact began c. 130,000 years ago, it seems to me.

Ken said...

they were smarter than you in many cases probably What!


They made the comment that if post-contact Neanderthals had been examined we may find that gene flow had moved in that direction too, which makes sense to me.

A purely Neanderthal population with no introgression would likely respond to environmental challenges by evolving along distinctly 'Neanderthal' lines to a greater extent than one that had hybridized; I believe there is some evidence that the north west European Neanderthal type did develop into the most extreme version of the Neanderthal.

They were much stronger, remember? If anything H. sapiens would be the scared ones.

Up close yes and that supports my contention that if humans tried to get jiggy with a Neanderthal they would be seriously injured. The main thing to remember about the interactions is Neanderthals were defenceless against humans' ability to throw spears while maintaining a safe distance with their superior mobility. By my way of thinking Neanderthals would have regarded humans as a deadly dangerous predator and be panic stricken when they saw one. Is there a precedent for a animal to hybridize with a species that preys on adult members of its species?

The 'humans ' who hybridized with Neanderthals were obviously not regarded as a much of a threat but maybe they were not behaviorally modern enough to want to hunt Neanderthals. The fully behaviorally modern humans of Europe would have been killing Neanderthals for sport.

Ken said...

They are reconstructions only: creative exercises. The real thing are the bones and they look somewhat less 'human' than the reconstructions.

Neanderthals - what they really looked like

Another explaination for a lack of introgression in Neanderthals would be that the humans who were mated with were subsequently eaten.

Maju said...

Ken: that link is racist defamatory shit. Using a gorilla template with a ferocious expression and FELINE or SERPENTINE RED EYES is maybe good for Hollywood but for science it's pure crap.

You also make the same absurd and potentially insulting claim (remember that there are many "Neanderthal spawn" over here, including me). I really think that you need to provide evidence for your "natural predator" nonsense (lol, they didn't even co-exist for long!) or abide by the clause of no racism and the unspoken one of seriousness.

I want serious and respectful commentators.

"What!"

That. Neanderthals were certainly in the human range of intellectual development. Many were smarter than you because you are obviously no Einstein.

The fact that you swallow the nonsense claims of that Vendramini is proof.

No self-respecting Neanderthal would believe that shit, really!

First of all the template, if not H. sapiens, should be a Pan (chimp and bonobo). But really our species is the closest thing. If anything it'd be 7 parts H. Sapiens, and 1 part Pan genus. They are slightly closer (9-1) in the human-specific HAR regions (so they were 90% human in comparison with chimps in that critical aspect) and had evolved in a parallel direction as H. sapiens (unlike Pan, specially chimps) towards larger brains.

However they had been living some 1 million years in colder conditions, so I can accept the concept of fur as possibility.

A much more serious report on Neanderthal variable representation has been made in the last several weeks by Millán Mozota (http://timoneandertal.blogspot.com/ - several recent articles, in Spanish but most interesting are the images).

Ken said...

Racist is the wrong term as there is no question that Neanderthals were a different species; Jane Goodall saw a chimp mating with a baboon in the wild you can't call them the same species on that basis. The existence of baboon DNA in Kipunji certainly doesn't mean they are the same species.

The night vision eyes are silly I agree but the size of the orbits is not human Chapelle aux saints. I don't know what the noses looked like and neither does anyone else, however:- Architecture of the nasal complex in Neanderthals: comparison with other hominids and phylogenetic significance.
that Neanderthals do indeed possess a configuration that is unique among hominids
So I very much doubt that Neanderthals' noses bore any resemblance to that of any modern human. Neanderthal Skeletal Structure and the Place of Homo Neanderthals in European Hominid Phylogeny
a recent full-body skeletal reconstruction that not only highlights the extreme differences between the highly apomorphic H. sapiens and H. neanderthalensis in the construction of the thorax and pelvic girdle, but strongly suggests significant gait differences between the two species that add to the probability that the two kinds of hominid would not have recognized each other as breeding partners.


Neanderthal could not possibly have remained a distinct species alongside modern humans if they were just sturdy broad faced versions of us which is the way they are depicted in almost all the modern reconstructions on the Millán Mozota link. The creationists and the Neanderthal experts are on the same page when it comes to minimizing the ape like qualities of Neanderthals.

Vendramini's reconstruction is tendentious but show me one that isn't, it looks ape like but you yourself said
78 alleles (table 2) that are fixated in the derived (non-Chimpanzee) form in the species Homo sapiens exclusively and found in their ancestral state among Neanderthals. Many are not really known their role but others seem to accumulate in certain processes such as skin (sweat...), melanin, smell, vision, sperm motility, hormonal and cellular division regulatory processes. This suggests me that there were some marked biological and appearence differences among the two species in spite of the proximity.


I don't see how you can know that and believe that the establishment reconstructions - which go so far as to give then recognizably European features -bear any resemblance to the real thing.

If you do then you surely are an Albert Einstein.

Maju said...

I am of the opinion that Neanderthals were a different species but 'species' is just a word anyhow. There's other very qualified people who think they were a different subspecies.

Whatever the case there is racist, specist or generally xenophobic intent not in any subtle manner but in a quite insulting one. And insulting to our intelligence as well.

I am not the least happy about that, really. Respect.

Eat them if need be but with due respect.

"The night vision eyes are silly"...

They are intended to create fear and difference and then present that illusion as if you recognize the instinctive enemy... which is surely a snake or a crocodile.

It's a very elaborated manipulation presented as 'the truth (TM)'. It's really evil!

It's clearly not a Neanderthal but an elaboration on the myth of King Kong.

But then you look at the mouth and it's like WFT, it doesn't even have fangs. And then you see the gorilla and then you notice the impossible SF eyes and the scam is revealed.

"Architecture of the nasal complex in Neanderthals: comparison with other hominids and phylogenetic significance.
that Neanderthals do indeed possess a configuration that is unique among hominids

"So I very much doubt that Neanderthals' noses bore any resemblance to that of any modern human".

I agree but neither with any other ape. Also the main difference is the organization of an internal protuberance.

I am of the opinion also that anatomically they appear as a different species and that, also for that reason, they must have evolved autonomously for some one million years and not just 400,000. But it doesn't make much difference: they were humans.

A different human species is still people like us... or almost.

"Vendramini's reconstruction is tendentious"...

Is not a "reconstruction" but true blood libel. The difference is the intent, which is blatantly mischievous and showing clear intent to deceive.

Maju said...

"... you yourself said
78 alleles (table 2) that are fixated in the derived (non-Chimpanzee) form in the species Homo sapiens exclusively and found in their ancestral state among Neanderthals".

But I am underlining the differences.

Notice that Neanderthals are very high (above the average genome distance) and akin to us in the HARs, which are regions that show specifically rapid evolution in our line and surely more directly associated to what we understand for being human. They may have some differences but they are very much like us.

I know it's a challenge to understand what's being like but not quite (for just a bit) human but the interpretation has to be reasonable and respectful.

What you have thrown here is an abuse, an insult to humankind. And not because it is extreme but because it has very evil intent.

It may be sophisticated trolling but trolling anyhow.

"I don't see how you can know that and believe that the establishment reconstructions - which go so far as to give then recognizably European features -bear any resemblance to the real thing".

I don't give much credence to reconstructions of any sort but there are things we know. For example, they had experienced depigmentation as we have, they had evolved some traits as light skin and, relatedly, hair and possibly eyes too. That doesn't mean that most Neanderthals were redhaired and had blue eyes but probably there were some of those too.

I disagree with many other issues and I do consider that they might have got body hair (but there are also reasons to think they did not, such as the use of fire and their African ultimate origins).

They probably were more different than some of the idealistic reconstructions but that doesn't mean we have to go to the opposite extreme of unbelievable ape-ification and gratuitous accusations of predators. They were competitors or allies but they were never our predators (though cannibalism used to be relatively frequent in our species).

So I close as this began: I don't believe in the usual reconstructions.

Ken said...

Maju, they couldn't throw spears and could barely run and jump, they had no tailored clothing ( no needles) so they must have been furry as bears. They had no untended devices like traps.

Maju said...

They could have perfectly used furs in a simple manner and their metabolism surely provided a lot of heat. Needles are to create tightly fit clothes but you can go with relatively simple capes and skirts around.

But whatever the case in this aspect they did use traps: they rounded horses en masse and pushed them through cliffs and such. Same with mammoths.

And don't forget it: their brain size was surely larger than yours. If chimpanzees are quite smart already and bonobos also plus highly sensible and empathic, what makes you think Neanderthals with their large brains and close relationship with us were stupid or something.

You claim they could not run but that's also an absurd claim. It's like looking at a bear and thinking it's slow and can't climb a tree. You are simply very wrong: you want to believe that but you have nothing to support that Neanderthals were dumb or insensible.

I'm fucking tired of people who just want to insult others because of their differences. It's a very petty attitude proper of petty beings who hide their complex of inferiority behind the damn fucking group identity. You have already a long history of doing that, so I wouldn't mind if you'd stop frequenting over here, really.

terryt said...

"Is there a precedent for a animal to hybridize with a species that preys on adult members of its species?"

I don't know of any evidence at all that shows modern humans preyed upon Neanderthals. Even the odd example of spear wounds could have been inflicted by other Neanderthals in territorial disputes.

"Racist is the wrong term as there is no question that Neanderthals were a different species"

On the contrary. It is only the assumption that we are somehow a special and superior species that demands most of us need to believe Neanderthals to be a separate species from us. We actually have no evidence one way or the other, although if the recent research indicating hybridisation pans out then modern humans and Neanderthals obviously were merely subspecies.

"suggests significant gait differences between the two species that add to the probability that the two kinds of hominid would not have recognized each other as breeding partners".

Some inconsistency here. Earlier you wrote:

"Jane Goodall saw a chimp mating with a baboon in the wild"

Surely these two species are more different than modern humans and Neanderthals, so I don't see any chance that mere gait would put them off.

"They had no untended devices like traps".

We don't know that either.

"they had no tailored clothing ( no needles) so they must have been furry as bears".

The Maori of New Zealand had no tailored clothing or needles either, but they were certainly not as 'furry as bears'. But from what I've read here I guess Ken would be prepared to consider them to be a separate species from Europeans.

Ken said...

Trinkaus (1995) analyzed patterns of injury in Neandertals and determined that their patterns of injury were highly unusual in comparison to most human groups (including some ancientgroups), and he concluded that Neandertal hunting involved close contact with angry medium-sized ungulates, and that Neandertal technology may have limited them to close range hunting.

Something kept modern humans out of Europe for a long time so it was likely Neanderthals who clearly were more than a match for humans back then. Later they were maybe about equal and that's when the breeding too place.

"Joyce said the best explanation for the variations was that our human ancestors and the archaic species interbred during two periods after the first Homo sapiens had left Africa: the first in the Mediterranean around 60,000 years ago, and the second in eastern Asia about 45,000 years ago"

However the later humans were too much for Neanderthals

Experimental evidence concerning spear use in Neandertals and early modern humans

Human Spear Likely Cause Of Death Of Neandertal

How Neanderthals met a grisly fate: devoured by humans

Morphological Differences in the Parietal Lobes within the Human Genus

"The role of the upper parietal lobule in the recognition and codification of the outer spatial environment and the associated integration between the outer frame and the inner perceptions would seem to indicate that such morphological changes may also have been related to important neurofunctional differences"

Neanderthals
"The forests on which they depended began to recede, giving way to open plains. Here, Professor John Shea believes, the Neanderthal thrusting spear and ambush strategy did not work. Neanderthals retreated with the forests, their population falling as their hunting grounds shrank.

By comparison, modern humans made lighter stone points that could be fitted on to lighter spear shafts. These could be thrown, enabling our ancestors to hunt more effectively in an open landscape.

Hunting in an open landscape also required high levels of mobility to follow migrating herds, and the agility to throw the spears themselves. So the question for our team was: how did Neanderthal stand up to our ancestors in agility?

Analysing the inner ear of a Neanderthal, Professor Fred Spoor, from UCL, has discovered clues to Neanderthal's agility.

The semi-circular canals of the inner ear provide us with our sense of balance, and by studying a range of animals, Spoor, has found a high correlation between the size of the canals and agility. Throughout human evolution, our canals seem to have increased in size as our agility has increased.

But Neanderthals have smaller canals than modern humans, and even earlier ancestors suggesting they were less agile.

Returning to the skeleton, Professor Trenton Holliday found an explanation for this - that the short limbs and wide pelvis of our Neanderthal would have resulted in less efficient locomotion than modern humans.
"