HST and Scladina Neanderthals

A A recent paper by Stephane Peyregne et al., (Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe, Science Advances 26 Jun 2019: Vol. 5, no. 6, eaaw5873 DOI: 10.1126/sciadv.aaw5873) looked into the mitochondrial DNA (mtDNA) of some ancient European remains and compared them to that of modern humans, Neanderthals and Denisovans.

What they found is indeed interesting, and unexpected.

The team sampled the remains of two Neanderthal people, which lived roughly at the same time (some 125,000 years ago), relatively close to each other in Western Europe: a male femur (thigh bone) discovered in the Hohlenstein-Stadel Cave, Germany, back in 1937 -this sample was named HST. They also analyzed a jaw bone belonging to a girl found in 1993 in Scladina, Belgium.

The mtDNA of the Scladina girl and the HST man, both from Western Europe, were most similar to the mtDNA of the Altai Neandertal (from the Altai region in Asia), 3,300 miles (5.300 km) west of Scladina and Hohlenstein-Stadel.

Their mtDNA was quite different from the mtDNA of later European Neanderthals that lived in the same region 80,000 years later.

HST and its unique mtDNA

The HST an carried mtDNA that was very different from that of all other Neanderthals, it had more than 70 mutations that distinguish it from the others' mtDNA. The bone was dated to approximately 124 kya. (62 to 183 kya), but its mtDNA split from that of other humans 270 kya.

The girl's remains are of a similar age: 127 kya (95 to 173 kya) but her mtDNA was more similar to that of an Asian Altai Neanderthal.

In fact both Scladina and the Altai Neanderthal grouped together in a branch of their own, with HST at the root and all other later Neanderthals on a separate branch.

The image below shows the branch that groups the Scladina girl with Atai Neanderthals and the HST Branch (inside the red square). As you can see, they are quite differentiated from that of all the other Neanderthals and Modern Humans (we are shown on the upper part of the diagram).

MtDNA of Neanderthals, Sima de los Huesos, Denisovan and Modern Humans

The fact that these three older Neanderthals are grouped together (see red square in image above) means that they share a common lineage of mtDNA; they all lived more or less at the same time (some 125 kya) and spanned a wide geographic area from the North Sea to the Altai in Siberia.

All more recent Neanderthals who lived roughly 40,000 years ago (green square in the image above) shared a common ancestor who lived some 97 kya, and belong to a branch that diverges from that of these three older Neanderthals.

These "modern" Neanderthals' mtDNA is derived from that of the "older" group.

The interesting part is that the Denisova Neanderthal (see "Denisova 11" in the image) which lived 90 kya in the Denisova cave in Central Asia, and is a hybrid of Denisovan father and a Neanderthal mother, has mtDNA which is closer to the more recent Neanderthals of Western Europe than to the Altai Neanderthal that lived in that same Denisova cave! 120,000 years ago.

This means that the ancient mtDNA of Altai Neanderthals was replaced by the "new" mtDNA shared by Denisova 11 and all other modern Neanderthals, so these later western European Neanderthals migrated east into Siberia and repopulated the Altai.

What about the Nuclear DNA?

The team looked into the nuclear or autosomal DNA of both Scladina and HST specimens and compared them with that of other Neanderthals.

They found that from a nuclear DNA point of view HST and Scladina were "more closely related to Vindija than they are to the Altai Neandertal". Vindija is a cave in Northern Croatia.

We see that all Neanderthals, old and recent share a common root for their nuclear DNA, but there are two branches: one with the Altai Neanderthal, and the other with all the other Neanderthals.

So it may be reasonable to suppose that all known Neanderthals (old and recent) share a common origin, and that it split as they migrated into Western Europe (HST and Scladina) and Siberia (Altain Neanderthals), this explains their branching.

Regarding the Atai Neanderthal, (see Prüfer K, Racimo F, Patterson N, et al. The complete genome sequence of a Neanderthal from the Altai Mountains, Nature. 2014;505(7481):43–49. doi:10.1038/nature12886) it was found to be (see Figure 2b in that paper) on the most diverged and basal branch within Neanderthal's nuclear DNA and therefore furthest away from the Vindjia specimens).

See image below, which I adapted from (here) and Fig. 2 of Peyregne et al.; it depicts the Nuclear DNA branching.

So we can imagine a very early migration of Neanderthals into Siberia (ancestral to Altai Neanderthal) who did not leave descendants.

The Western Neanderthal population (which included HST and Scladina) had settled Europe 125 kya and its descendants later migrated across Eastern Europe, entered Asia and settled in the Altai region replacing this eastern population in Asia.

The very odd HST mtDNA

The very divergent mtDNA carried by HST split from that of all other Neanderthals some 270,000 years ago. This is far older than expected by the team (they'd estimated less than 150 kya).

And they believe that this is due to the fact that "HST carries some ancestry from a genetically distant population.".

They propose two scenarios:

1. "Admixture between Neandertals and ancestors or relatives of modern humans could explain the origin of this later Neandertal mtDNA... If several mtDNAs were introduced into the Neandertal population by such a putative gene flow, then the deeply divergent mtDNA in HST may represent the remnants of the mitochondrial diversity of this introgressing population... This would imply that this admixture into Neandertals occurred later than the previously suggested lower boundary of 270 ka ago".
2. "An alternative source for the deeply divergent mtDNA in HST could be an isolated Neandertal population, for example, a population that separated from other Neandertals before the glacial period preceding HST and Scladina (~130 to 190 ka ago...). Such an isolated population may have preserved the mtDNA that was later re-introduced during a warmer period between 115 and 130 ka ago (the “Eemian” period) when these populations met again and gene flow resumed."

Discussion

I ask: Can we reasonably expect a group to remain in isolation for 15,000 to 75,000 years and maintain their mtDNA without mutations? This "isolated group"notion is identical to the Beringian Standstill Hypothesis which states that the humans who would people America remained isolated in Beringia for tens of thousands of years.

But the Beringian mutated while the isolated Neanderthals did not! This is weird, same situation and two different outcomes:

The Beringians suffered mutations that gave their descent, the modern Native Americans a distinctive mtDNA that is not found in Asia is said to have arisen during the "standstill": after their ancestors left Asia, but before they dispersed into the Americas.

Yet the isolated ancestors of the Neanderthals retained their original mtDNA without anyn mutations.

So in one case it is mtDNA "stasis" and in another "mutation". You can't have it both ways. One or other or perhaps even both theories are wrong.

In this context, the admixture theory seems reasonable, but why should we have to assume admixture? Let's read it in the paper's words:

"It seems unexpected that HST carries an mtDNA lineage that diverged ~270 ka ago from other mtDNAs, given the recent population split times from the Vindija ancestors and the low levels of genetic diversity in the nuclear genomes of Neandertals".

In other words, as their nuclear genome is very similar to that of the Vindija Neanderthals, who lived 80 ky later than HST, their mtDNA can't be 270 ky old.

They add:

"An explanation could be related to a replacement of mtDNAs in Neandertals that has been suggested to explain the discrepancy between the mtDNA divergence time (<470 ka ago) and the population split times based on nuclear DNA (>520 ka ago) between modern humans and Neandertals.
The Sima de los Huesos hominins, and perhaps other early Neandertals, carried mtDNAs that shared a common ancestor with Denisovan mtDNAs more recently than with those of modern humans, whereas later Neandertals carried mtDNAs that shared a more recent common ancestor with the mtDNAs of modern humans.
Admixture between Neandertals and ancestors or relatives of modern humans could explain the origin of this later Neandertal mtDNA".

We see that once again there is a discrepancy between mtDNA and nuclear DNA divergence dates, you'd expect both to be the same age. In this case it is 470 ky vs. 520 ky.

In a previous post on this subject (Sima de los huesos is now.... closer to Neanderthals than Denisovans!) I gave an explanation for this conundrum as follows:

The common mtDNA shared by Denisovans and Sima de los Huesos but not the nuclear DNA could be explained as follows:

• A native archaic population lives in Eurasia (descendants of H. erectus?) with its specific autosomal DNA and mtDNA; they are the ancestors of Denisovans and a pre-Sima de los Huesos people.
• A later wave of proto-Neandertal reach Europe, they are more successful and breed with the native women (kill the men and keep the women) of the native pre-Sima de los Huesos stock.

The original archaic mtDNA is preserved in their offspring -since it is transmitted by the mothers to their children-, but the nuclear DNA is now admixed with that of the proto-Neandertals.

After many generations we have a European lineage with mtDNA similar to the original ancient stock (Homo erectus?) and therefore shared with Denisovans, but a nuclear DNA which will be more like that of Neanderthals which were formed by this admixture.

A similar event must have taken place with the Neanderthals.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2019 by Austin Whittall © 

Haplogroups of Humans and Neanderthals and Denisovans: mtDNA and Y chromosomes)

I have just read a paper that refutes my closing comments of this 2014 post: A shared Y chromosome lineage Neanderthals and Modern Humans but it does support the image I posted in it, pictured below:

Hypothetical Y chromosome phylogenetic tree for humans and Neanderthal. Copyright © 2014 by Austin Whittall

I explained the image as follows: "the ancestral population of both humans and Neanderthals, split into two groups: one that would later evolve into modern humans, and another that would evolve into Neanderthals. Each would carry, in the beginning, the "original" archaic Y chromosome of the ancestral population, which, as each lineage accumulated mutations due to chance and positive selection would begin to grow in different directions, forming two distinct branches, which then in turn would continue branching as more mutations appeared."

And that is what the paper states (Reconstructing the genetic history of late Neanderthals by Mateja Hajdinjak et al., 652 NATURE VOL 555 29 march 2018, doi:10.1038/nature26151.) Figure 2 in the article is shown below, and it agrees with the Y chromosome tree that I proposed back in 2014:

Phylogenetic trees for mtDNA, autosomal DNA and Y-chromosome of humans, Neanderthals, Denisovans and Sima de los Huesos hominin. From Hajdinjak et al.

The Human haplogroups are on distinct branches, well away from those of the older hominins.

See this Sept. 2020 update.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2018 by Austin Whittall © 

On human and Neanderthal - Denisovan mtDNA

There is no evidence at all of extant Neanderthal mtDNA in modern humans. This seems quite surprising, and many explanations have been offered. But the most simple and clear cut one is, in my opinion, the lack of enough samples of Neanderthal mtDNA tested to date. And this is precisely what this paper says: No Evidence of Neandertal mtDNA Contribution to Early Modern Humans, by David Serre, Andre Langaney, Mario Chech, Maria Teschler-Nicola, Maja Paunovic, Philippe Mennecier, Michael Hofreiter, Göran Possnert, Svante Pääbo (Published: March 16, 2004https://doi.org/10.1371/journal.pbio.0020057)

They clearly state the following:

"..Under the model of a constant human effective population size (Tavare 1984; Nordborg 1998) of 10,000 over time (Figure 4A), any contribution of Neandertal mtDNA to modern humans 30,000 years ago larger than 25% can be excluded at the 5% level (Figure S3). A more realistic scenario may be that the spread of modern humans was accompanied by an increase in population size before and during their migration out of Africa and subsequent colonization of western Eurasia (see Figure 4B). In that case, the Neandertal contribution that can be excluded is smaller (i.e., less gene flow could have taken place)...
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... ."

The authors indicate that the Neandertal fossil remains carry "closely related mtDNAs that are not found among current humans", in fact all reads are very similar to each other and, different to the standard modern human reference.

They mention the possible causes for this lack of Neanderthal mtDNA in H sapiens: "...such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils.".

Both causes seem very reasonable and the authors fin that this "... excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution."

So, after all, there may have been a small introgression of Neanderthal mtDNA into us.

An intersting point to ponder is that "Although mitochondria retain their own genome, the vast majority of the >1000 proteins that function in mitochondria are encoded in the nucleus" (from The Mitonuclear Dimension of Neanderthal and Denisovan Ancestry in Modern Human Genomes. Joel Sharbrough Justin C. Havird Gregory R. Noe Jessica M. Warren Daniel B. Sloan. Genome Biology and Evolution, Volume 9, Issue 6, 1 June 2017, Pages 1567–1581, https://doi.org/10.1093/gbe/evx114).

This means that the mitochondrial genes and the nuclear genes that encode these proteins (known as N-mt genes), proteins used by the mitochondria, have to adapt to each other during episodes of introgression in order to function correctly and not cause the death of the hybrid individual.

Sharbrough et al then apply this concept to Neanderthal ⁄ Denisovan admixture with H. sapiens:

"The potential for mitonuclear interactions among hominins is of interest because, unlike in the nuclear genome, there has not been any detectable mtDNA introgression from Neanderthals or Denisovans into modern human populations (Krings et al. 1997; Serre et al. 2004). Regardless of what has caused this lack of mtDNA introgression, one consequence is that all introgressed Neanderthal and Denisovan nuclear alleles must function on a modern-human mitochondrial background..."

In other words if there is no Neanderthal or Denisovan mtDNA in humans, our modern mtDNA however must have had to adapt to the N-mt genes that did introgress from our older relatives (Neanderthals and Denisovans). And their paper looks into this.

They concluded that "... genes involved in mitochondrial function may have been subject to distinct selection pressures during the history of introgression from archaic hominins but that mitonuclear incompatibilities have had, at most, a small role in shaping genome-wide introgression patterns, perhaps because of limited functional divergence in mtDNA and interacting nuclear genes."

In other words there wasn't much incompatibility between the mtDNA and the N-mt genes after all! And this was because our and their mtDNA and nuclear genes were, or are, very similar. Which is what you'd expect anyway, we all branched off from the same tree not that long ago (say 750 Ky).

I do look forward to mtDNA sequences more complete in nature, from more individuals (archaic H. sapiens and Neanderthal & Denisovans), who knows, we may actually find one with a shared mtDNA Haplogroup...

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall © 

Sima de los Huesos remains, Neanderthals, Denisovans and their nuclear and mtDNA

A very interesting paper published in Nature (Matthias Meyer et al.) has confirmed that the Sima de los Huesos remains, that are 430 ky old, have mtDNA that resembles that of Denisovans more closely than that of the Neanderthals. But, their nuclear DNA is more similar to that of Neanderthals than to Denisovan nuclear DNA.

Since the Sima de los Huesos hominins are supposed to be the ancestors of Neanderthals it is reasonable that their nuclear DNA is similar to that of Neanderthals and different from Denisovans. But why is the relationship regarding mtDNA exactly the opposite?

The paper offers three explanations:

1. The Sima de los Huesos people had two very diverging mtDNA types, one leading to Neanderthals the other to Denisovans, and these samples are of the first kind.
2. Some "other" hominin contributed its mtDNA to both Denisovans and Sima de los Huesos people
3. The original proto Neanderthal mtDNA was inherited by their Neanderthal descent but was completely diluted by later inflow of Neanderthal mtDNA from Africa, which we find in more recent Neanderthals.

In science, the breakthroughs come from finding the correct answer to discrepancies like these. So it is very exciting and who knows what will eventually be learned from this!.

Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall ©