Thursday, April 7, 2016

Ancient Neanderthal Y-DNA

We finally have ancient Neanderthal Y-DNA (the previous five autosomal ancient DNA samples from Neanderthals were from women) and it is very much as we expected it to be.

The Neanderthal Y-DNA is much more ancient than the most basal known modern human Y-DNA haplogroup A00 (of which only a dozen or two modern bears have been found) for which TMRCA is about 280,000 years ago.  Y-DNA A00, in turn, is much more ancient than any other modern human Y-DNA haplogroups (the most basal of which are other subtypes of Y-DNA haplogroup A).*  Its mutation estimated age largely corroborates estimates of the split of the most recent common ancestor of modern humans and Neanderthals from autosomal DNA and mtDNA estimates.  The estimated divergence date of Neanderthal mtDNA from modern human mtDNA is 400,000 to 800,000 years ago, with a mean just 12,000 years different from the 588,000 years ago estimate based upon Y-DNA.**

No modern human has any Neanderthal Y-DNA or any Neanderthal mtDNA.  Essentially all non-African modern humans have a low percentage of introgressed Neanderthal autosomal DNA in all other chromosomes.  The paper notes based upon its examination of protein coding differences that could have impacted male hybrid fertility that:
It is tempting to speculate that some of these mutations might have led to genetic incompatibilities between modern humans and Neandertals and to the consequent loss of Neandertal Y chromosomes in modern human populations. Indeed, reduced fertility or viability of hybrid offspring with Neandertal Y chromosomes is fully consistent with Haldane’s rule, which states that “when in the [first generation] offspring of two different animal races one sex is absent, rare, or sterile, that sex is the [heterogametic] sex.”
This also corroborates that Y-DNA A00 is unlikely to be an introgression from an archaic hominin species and is instead simply a basal Y-DNA lineage that has survived at a very low frequency despite the fact that all but one of the modern human Y-DNA lineages that emerged over the intervening ca. 100,000 years between it and the next most basal Y-DNA lineage have gone extinct leaving no descendants.
Sequencing the genomes of extinct hominids has reshaped our understanding of modern human origins. 
Here, we analyze ∼120 kb of exome-captured Y-chromosome DNA from a Neandertal individual from El SidrĂ³n, Spain. 
We investigate its divergence from orthologous chimpanzee and modern human sequences and find strong support for a model that places the Neandertal lineage as an outgroup to modern human Y chromosomes—including A00, the highly divergent basal haplogroup. 
We estimate that the time to the most recent common ancestor (TMRCA) of Neandertal and modern human Y chromosomes is ∼588 thousand years ago (kya) (95% confidence interval [CI]: 447–806 kya). This is ∼2.1 (95% CI: 1.7–2.9) times longer than the TMRCA of A00 and other extant modern human Y-chromosome lineages. 
This estimate suggests that the Y-chromosome divergence mirrors the population divergence of Neandertals and modern human ancestors, and it refutes alternative scenarios of a relatively recent or super-archaic origin of Neandertal Y chromosomes. 
The fact that the Neandertal Y we describe has never been observed in modern humans suggests that the lineage is most likely extinct. 
We identify protein-coding differences between Neandertal and modern human Y chromosomes, including potentially damaging changes to PCDH11Y, TMSB4Y, USP9Y, and KDM5D. Three of these changes are missense mutations in genes that produce male-specific minor histocompatibility (H-Y) antigens. Antigens derived from KDM5D, for example, are thought to elicit a maternal immune response during gestation. It is possible that incompatibilities at one or more of these genes played a role in the reproductive isolation of the two groups.
Fernando L. Mendez, G. David Poznik, Sergi Castellano, Carlos D. Bustamante, "The Divergence of Neandertal and Modern Human Y Chromosomes", AJHG Volume 98, Issue 4, p728–734 (April 7, 2016) (open access).

* Wikipedia summarizes the state of the research on TMCRA date for the most basal Y-DNA other than Y-DNA A00 and the most basal mtDNA (citations omitted):
Current (as of 2015) estimates for the age for the Y-MRCA are roughly compatible with the estimate for the emergence of anatomically modern humans some 200,000 years ago (200 kya), although there are substantial uncertainties. 
Early estimates published during the 1990s ranged between roughly 200 and 300 kya, Such estimates were later substantially corrected downward, as in Thomson et al. 2000, which proposed an age of about 59,000. This date suggested that the Y-MRCA lived about 84,000 years after his female counterpart mt-MRCA (the matrilineal most recent common ancestor), who lived 150,000–200,000 years ago. This date also meant that Y-chromosomal Adam lived at a time very close to, and possibly after, the migration from Africa which is believed to have taken place 50,000–80,000 years ago. One explanation given for this discrepancy in the time depths of patrilineal vs. matrilineal lineages was that females have a better chance of reproducing than males due to the practice of polygyny. When a male individual has several wives, he has effectively prevented other males in the community from reproducing and passing on their Y chromosomes to subsequent generations. On the other hand, polygyny does not prevent most females in a community from passing on their mitochondrial DNA to subsequent generations. This differential reproductive success of males and females can lead to fewer male lineages relative to female lineages persisting into the future. These fewer male lineages are more sensitive to drift and would most likely coalesce on a more recent common ancestor. This would potentially explain the more recent dates associated with the Y-MRCA. 
The "hyper-recent" estimate of significantly below 100 kya was again corrected upward in studies of the early 2010s, which ranged at about 120 kya to 160 kya. This revision was due to the discovery of additional mutations and the rearrangement of the backbone of the Y-chromosome phylogeny following the resequencing of Haplogroup A lineages. In 2013, Francalacci et al. reported the sequencing of male-specific single-nucleotide Y-chromosome polymorphisms (MSY-SNPs) from 1204 Sardinian men, which indicated an estimate of 180,000 to 200,000 years for the common origin of all humans through paternal lineage. . . . Also in 2013, Poznik et al. reported the Y-MRCA to have lived between 120,000 and 156,000 years ago, based on genome sequencing of 69 men from 9 different populations. In addition, the same study estimated the age of Mitochondrial Eve to about 99,000 and 148,000 years. As these ranges overlap for a time-range of 28,000 years (148 to 120 kya), the results of this study have been cast in terms of the possibility that "Genetic Adam and Eve may have walked on Earth at the same time" in the popular press. 
The announcement of yet another discovery of a previously unknown lineage, haplogroup A00, in 2013, resulted in another shift in the estimate for the age of Y-chromosomal. Karmin et al. (2015) dated it to between 192,000 and 307,000 years ago (95% CI). 
The same study reports that non-African populations converge to a cluster of Y-MRCAs in a window close to 50kya (out-of-Africa migration), and an additional bottleneck for non-African populations at about 10kya, interpreted as reflecting cultural changes increasing the variance in male reproductive success (i.e. increased social stratification) in the Neolithic.
** Per Wikipedia (not updated for the most recent data from this paper) the dates of the earliest Neanderthal archaeological record (with a total of abotu 400 sets of Neanderthal remains recovered to date) is as follows (citations omitted):
The first humans with proto-Neanderthal traits are believed to have existed in Eurasia as early as 350,000–600,000 years ago with the first "true Neanderthals" appearing between 200,000 and 250,000 years ago. . . .
Comparison of the DNA of Neanderthals and Homo sapiens suggests that they diverged from a common ancestor between 350,000 and 400,000 years ago. 
This ancestor was probably Homo heidelbergensis. Heidelbergensis originated between 800,000 and 1,300,000 years ago, and continued until about 200,000 years ago. It ranged over Eastern and South Africa, Europe and Western Asia. Between 350,000 and 400,000 years ago the African branch is thought to have started evolving towards modern humans and the Eurasian branch towards Neanderthals. Scientists do not agree when Neanderthals can first be recognised in the fossil record, with dates ranging between 200,000 and 300,000 years BP.
Ancient DNA from H. Heidelbergensis has established that it was an ancestor of the Neanderthals, and that Denisovans, for whom we also have ancient DNA, are not members of the species H. Heidelbergensis.

Post-Script on Neanderthal mtDNA

I've long advocated for Haldane's Law as the source of a lack of Neanderthal Y-DNA in modern humans and it is nice to see that hypothesis largely confirmed based upon the protein coding of actual Neanderthal Y-DNA.

So, why is there no Neanderthal mtDNA in modern humans?

My hypothesis, which is as solid as anything else out there at this point, is that overwhelmingly, Neanderthal-modern human admixture in both directions involved sexual encounters of short duration (probably some combination of rapes and brief flings) that did not continue through the birth of a child. Further, that in any instances where there was a prolonged nuclear family relationship that such relationships were matrilocal (I suspect that this was very rare, but if it did happen at any frequency, it wouldn't change the result.)

In this scenario, mother's of Neanderthal-modern human hybrids would stay with the tribe of the mother, rather than the tribe of the father.  Thus, hybrid Neanderthal-modern human children (all girls or infertile boys) with human mothers and hence modern human mtDNA would be raised in modern human tribes, while those with Neanderthal mothers and hence Neanderthal mtDNA would be raised in Neanderthal tribes.

The hybrid children in modern human tribes with modern human mtDNA contributed to current populations.  The descendants of hybrid children in Neanderthal tribes with Neanderthal mtDNA went extinct with the rest of the Neanderthal species.

It is possible that in some very rare instances a Neanderthal woman with hybrid children was incorporated into a modern human tribe, that her mtDNA was lost due to random drift (or, in part, because the daughters of Neanderthal women may have been at a selective disadvantage in a modern human tribe relative to other girls in the tribe).

But, while mtDNA lineages are lost much more often due to random drift than you would naively expect in stable populations, and are frequently lost in shrinking populations (e.g. those experiencing a population bottleneck), mtDNA lineages are much less likely to be lost due to random drift in expanding populations.  Yet, the modern human population outside Africa was probably expanding rapidly around the time of Neanderthal admixture.


terryt said...

"Indeed, reduced fertility or viability of hybrid offspring with Neandertal Y chromosomes is fully consistent with Haldane’s rule, which states that 'when in the [first generation] offspring of two different animal races one sex is absent, rare, or sterile, that sex is the [heterogametic] sex'."

To me that is a sufficient explanation. In most pairs of mammalian species male fertility is the first to drop off as the species become more separated in time. Obviously it is not a purely linear relationship as some species separated by as much as a million years do not exhibit male sterility, but in others it can be as little as half a million years, which is the time between modern and Neanderthal. I have read many ridiculous ideas of why the Neanderthal Y-DNA has died out such as the Anthropology blog, where they ignore the obvious:

If two species form hybrids where the F1 males are unable to reproduce then obviously just one male line will come to dominate even if hybrid females are able to successfully reproduce. But if hybrid individuals are accepted into the mother's species and just one of those species comes to dominate then the mt-DNA from the species that becomes extinct will also become extinct.

Ryan said...

"This also corroborates that Y-DNA A00 is unlikely to be an introgression from an archaic hominin species"

I think that would depend on your definition of archaic. If it's quite literally intermediate between modern humans and the modern human / Neanderthal common ancestor, I think that's a pretty interesting edge case.

terryt said...

I think it is becoming increasingly difficult to accept anything other than that the ancestors of modern humans must have moved into Africa some time after they split from Neanderthals. That is around half a million years ago. Neanderthals must have formed from Denisovans (most likely what used to be called H. heidelbergensis) somewhere in Eurasia. The separation of Neanderthals and moderns may simply have been caused by increasing aridity through the Sahara/Arabian Peninsula.