April 07, 2016

Neandertal Y-chromosome (finally)

It's been six years since the publication of the draft Neandertal genome, and one piece of the puzzle that's always been missing is the Neandertal Y-chromosome (unfortunately most of the Neandertals yielding data were female). But, the wait is finally over, with the first publication of Neandertal Y-chromosome data.

AJHG Volume 98, Issue 4, p728–734, 7 April 2016

The Divergence of Neandertal and Modern Human Y Chromosomes

Fernando L. Mendez, G. David Poznik, Sergi Castellano, Carlos D. Bustamante

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 Sidrón, 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.

Link

17 comments:

Mark Moore (Moderator) said...

Every study I have seen says that there is no detectable Neanderthal mtDNA in humans. That would seem to indicate that any Nuclear gene flow did NOT come from female Neaderthals mating with male humans. Now this study shows no crossover in the Y chromosome, indicating the gene flow did not come from male Neaderthals mating with female humans. Something does not add up here. Those are the only two ways gene flow is supposed to happen.

Did the genes come via viral infections crossing over and taking some DNA with it? Is there some other means? Do we just need more samples (obviously but still....)?

eurologist said...

~600,000 years ago is compatible with the documented co-evolution in brain cavity size between heidelbergensis and African specimen.

Bloodredskies911 said...

This is pretty much the worst, most ill-informed paper I've ever read.

That no Y-DNA from the +200,000 year old Sima de los Huesos population has yet to be found in modern humans should come as no surprise.


Neanderthals in Europe underwent a rapid population turnover 50,000 years ago corresponding to changing climatic conditions at that period. Neanderthals in the Levant and Central Asia are so morphologically distinct from their European counterparts that they were likely diverged from the Europeans genetically as far as early modern humans were from the same region.

http://www.mbe.oxfordjournals.org/content/early/2012/02/23/molbev.mss074.short?rss=1

Until someone gets Y-DNA from a late Neanderthal, European or otherwise, no one is fit to make the absurd and quite frankly outrageous declaration that Neanderthal Y lineages are extinct, based on an analysis of one of the earliest and most isolated populations of Neanderthals.

All that can be said with any meaningful degree of certainty is that the Neanderthal mitochondrial lineage is extinct. If modern humans and Neanderthals interbred, Y-DNA or mtDNA lineages must be present in a modern human somewhere. If it is not present, even in the genome of the archaic specimen Oase 1, who's base pairs indicate relation to a Neanderthal within 150 years, then that means they did not interbreed, because we aren't a different species, and a pure multiregional evolutionary scenario is what really happened.

Onur said...

This is pretty much the worst, most ill-informed paper I've ever read.

That no Y-DNA from the +200,000 year old Sima de los Huesos population has yet to be found in modern humans should come as no surprise.


Neanderthals in Europe underwent a rapid population turnover 50,000 years ago corresponding to changing climatic conditions at that period. Neanderthals in the Levant and Central Asia are so morphologically distinct from their European counterparts that they were likely diverged from the Europeans genetically as far as early modern humans were from the same region.

http://www.mbe.oxfordjournals.org/content/early/2012/02/23/molbev.mss074.short?rss=1

Until someone gets Y-DNA from a late Neanderthal, European or otherwise, no one is fit to make the absurd and quite frankly outrageous declaration that Neanderthal Y lineages are extinct, based on an analysis of one of the earliest and most isolated populations of Neanderthals.


Read the paper carefully. The Y-DNA sequence is not from the very old Sima de los Huesos Neanderthals but from a ∼49,000-year-old Neanderthal from El Sidrón, Spain. The El Sidrón Neanderthals are in the post-turnover cluster according to the paper you linked.

All that can be said with any meaningful degree of certainty is that the Neanderthal mitochondrial lineage is extinct. If modern humans and Neanderthals interbred, Y-DNA or mtDNA lineages must be present in a modern human somewhere. If it is not present, even in the genome of the archaic specimen Oase 1, who's base pairs indicate relation to a Neanderthal within 150 years, then that means they did not interbreed, because we aren't a different species, and a pure multiregional evolutionary scenario is what really happened.

Neanderthal genomes have been examined through all kinds of genetic tests: autosomal, mtDNA and Y-DNA. None of them has yielded any result supporting your pure multiregional evolutionary scenario, irrespective of the age of the Neanderthal tested. It is clear from the tests that Neanderthal and modern human lines parted ways hundreds of thousands of years ago and only mixed on rare occasions after their separation.

Tobus said...

@Mark Moore: Something does not add up here. Those are the only two ways gene flow is supposed to happen.
@Bloodredskies: If modern humans and Neanderthals interbred, Y-DNA or mtDNA lineages must be present in a modern human somewhere.

There are human samples from 5000ya whose y- or mt-DNA lineages are now extinct... there's simply no reason to expect a Neanderthal y/mt lineage to still exist in modern humans.

TNT said...

An unknown quantity of male neandertals mated with human females thus producing offspring. If said offspring were females then that will account for human mtdna lineages. Or if by chance a male hybrid had female offspring then there would account for human lineages.

Ross said...

Mark Moore "Did the genes come via viral infections crossing over and taking some DNA with it? Is there some other means? Do we just need more samples (obviously but still....)?"

Mark, I am half Irish. My mother's father was Irish, so I don't have an Irish Y chromosone. My father's mother was Irish, so I don't have an Irish mtDNA. However half my genes are still Irish. So the lack of Neandertal signature DNA could have happened by chance in a similar manner. Alternatively, it may be that modern humans have no Neandertal Y chromosones or mtDNA because they were in some way less fit than the sapiens version, and have died out because people with these genes were less able to survive.

GerardW1966 said...


Read the paper carefully. The Y-DNA sequence is not from the very old Sima de los Huesos Neanderthals but from a ∼49,000-year-old Neanderthal from El Sidrón, Spain. The El Sidrón Neanderthals are in the post-turnover cluster according to the paper you linked.

Nobody knows how old the El Sidron Neanderthals are. The dates are inconsistent; the original dating was was 10,000 ybp, now they're saying it's 45,000-52,000. The fact that the Neanderthal remains were found with Levallois rather than Chatelperronian toolkits suggests a much earlier dating.

Ryan said...

Until someone gets Y-DNA from a late Neanderthal, European or otherwise, no one is fit to make the absurd and quite frankly outrageous declaration that Neanderthal Y lineages are extinct, based on an analysis of one of the earliest and most isolated populations of Neanderthals.

We can all make that call pretty conclusively right now. Either Neanderthal Y-DNA is completely extinct, or it persists at such astronomically low levels that it just hasn't been sampled yet. We don't even need Neanderthal DNA to tell that - TMRCAs alone do. With the possible exception of A00, there is no archaic mitochondrial or Y chromosomal DNA detected in modern humans.

Anna said...

Mark -- You said, "Now this study shows no crossover in the Y chromosome, indicating the gene flow did not come from male Neaderthals mating with female humans."

This is certainly true, but only in the case of Male N/Female MH producing sons -- female infants would have the N X and the MH X, but the MH mtDNA.


To piggyback off of Onur, a very similar statement to the above applies to Bloodredskies911's comment: "If modern humans and Neanderthals interbred, Y-DNA or mtDNA lineages must be present in a modern human somewhere."

Again, this is only true if those interbreeding events either included Male N/Female MH producing sons, or Female N/Male MH producing females.
Yes it's sort of a long shot currently to say definitively that those interbreeding events were limited to those two outcomes, but the current genetic data does seem to point to that. There is always the potential that those lineages existed, and simply did not succeed for very long, and did not contribute in any significant way to our current gene pool.

It is also worth noting that a good part of the genetic comparison being done (especially through popular services such as 23andMe) is limited to a genome cobbled together from 3 female Neandertal individuals from Croatia.

matt said...

The probability of lack of male progeny after N generations for a given male individual is close to 1.0. From the abstract this paper suggests reasons why a female ancestor with modern humans mtDNA would have lower reproduction rates of males with Neanderthal fathers. That is just a theory of going from close to 1.0 probability of no Neanderthal yDNA present today to closer to 1.0 probability of no Neanderthal yDNA present today. As far as autosomal DNA these SNPs support female line(s) with modern human's mtDNA that was bred with Neanderthal males until the autosomal was dominantly Neanderthal. This would increase the likelihood of higher Neanderthal DNA in a population when the female line bred with human yDNA. Reich has already proposed mechanisms in which reduced human X chromosone reduces fertility in both male and female to the same effect.
Absolutely no surprise that neither Neanderthal yDNA or mtDNA is found today. http://www.sciencedirect.com/science/article/pii/S1040618212001085
A lot more mileage from looking for Neanderthal etc DNA in ancient humans.

http://dienekes.blogspot.com/2015/06/oase1-had-neandertal-ancestor-no.html

DocG said...

Mark Moore: "Did the genes come via viral infections crossing over and taking some DNA with it?"

Yes, that's possible. It's called "horizontal gene transmission" (HGT) and it's apparently been confirmed in humans. See Crisp, Alastair et al. 2015. Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Genome Biology 16:50.

"[F]ar from being a rare occurrence, HGT has contributed to the evolution of many, perhaps all, animals and . . . the process is ongoing in most lineages. Between tens and hundreds of foreign genes are expressed in all the animals we surveyed, including humans."

Mark Moore (Moderator) said...

So we have four "not that unusuals" and one "maybe HGT is responsible."

I see both sides. I can see how an individuals Y-dna or mt-DNA can be lost, but we are not dealing just with an individual here, but a species. IOW Ross has correctly pointed out that he does not have an Irish Y. But unless his father was SAN or Pygmy or A00 he as something very close. From what I can tell the results of the Y on this Neanderthal are NOT very close to any known AMH Y-DNA living or dead. So it wasn't just this one poor beast whose Y-DNA went extinct but all those of his kind as well. Same thing with mt-DNA.

Someone who can do the math better than me should compute the odds. 2% of genes in 6.5 billion people and zero Y-dna and zero mtDNA. That's in say 2,000 generations? And don't say "try winning 2000 coin tosses" because without birth control most of use would have heads and tails, boys and girls. I do anyway. The only way it makes sense to me is if there is a VERY limited number of introgression events in a VERY SMALL initial AMH population.

Luc Van Braekel said...

Mark Moore: "Those are the only two ways gene flow is supposed to happen."

No. Consider your 4 grandparents. Your Y-DNA comes from the father of your father. Your mt-DNA comes from the mother of your mother. If the father of your mother, or the mother of your father, were neanderthal, your autosomal DNA would contain neanderthal DNA, but your Y-DNA nor your mt-DNA would not contain neanderthal DNA.

It is entirely possible for Y-DNA or mt-DNA haplogroups of a certain population to be extinct, while some autosomal DNA of that same population remains. As for the probability of that to happen, I matt's comment is relevant.

Diomedes said...

As far as I know there is no evidence that suggests genes can transfer in anything outside of the viruses that show this ability the way you are saying. They copy and move DNA to different areas also, not creating new information and interjecting it into other organisms. This is a theory, and the so called "foreign genes" in "all animals including humans" is an equal amount of evidence that this doesn't happen at all, as it shows no exception but a consistency. This being "important to evolution" when it's not even proven to happen in anything outside of the microscopic life forms that have this ability is a bold statement that will expanded and changed upon continuously until some semblance of the truth is found hopefully.

Solar Physics said...

Mark, If male Neanderthals produced only female offspring with female modern humans, the offspring would have no Neanderthal Y-chromosome nor Neanderthal mtDNA. No idea if that is likely, but it is logically possible.

terryt said...

"If male Neanderthals produced only female offspring with female modern humans, the offspring would have no Neanderthal Y-chromosome nor Neanderthal mtDNA"

They don't actually have to produce only female offspring for the Y-DNA to disappear as it now appears likely that male hybrid offspring were infertile. Therefore their Y-DNAs would not be present in the next generation.