January 26, 2011

Is X-DNA lineage Neanderthal?

Upon the recent discoveries of Neanderthal and other archaic admixture in modern humans, it arose in the debates occasionally this almost forgotten matter of an X-linked haplotype that looked very much non-African. However Africa had only been sampled poorly back in that time and we lacked any confirmation on this haplotype being present or not in the Neanderthal genetic pool.

According to a new paper this X-DNA haplotype, known as B006, fits well with Neanderthal genetic data and is therefore a likely case of Neanderthal lineage among us.


Frequency of B006 worldwide

It was previously known that the lineage was most common among Europeans and Native Americans, though maybe most diverse in Central-NE Asia. Almost nothing was known then about its presence among South Asians or Australian Aborigines and the little knowledge of the African scatter (mostly among Burkinabe peoples, with one Ethiopian individual as well) has been confirmed, it seems.

But most importantly B006 shares both mutations divergent from the ancestral (Chimpanzee) form among all those analyzed in the Neanderthal genome. One is common to most modern human lineages but the other transition is unique to B006 and the Neanderthal lineage:

In the available Neandertal sequence (Green et al. 2010), there is information on 20 out of 35 dys44 polymorphic sites. These represent eighteen ancestral and two derived alleles, fully matching the corresponding sites of B006 (Table 1). One of the derived alleles, C of  rs6631517, is also shared with other dys44 haplotypes, whereas the second one, G of  rs11795471, is unique to B006 (the information on two remaining B006-polymorphisms is not available).

While not yet fully demonstrated (further B006 haplotypes should be considered along further Neanderthal ones as well), the idea, until now purely speculative, of this lineage being a Neanderthal one, clearly gains strength with this paper's work.

15 comments:

  1. Wow Maju very interesting! I remember we were talking about this lineage a few days ago. You said it was found mainly in Basques and Native Americans, but this new map shows it's present among all non-African populations plus north Africans.

    It's safe to claim neanderthal ancestry, or could it be descended from an archaic African population who left Africa earlier than other migrations? I yelling this to you ecause I read that this haplotype shows a colascence time with all other haplotypes much younger than what's expected for it's neanderthal origins (about 100-200K).

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  2. The map I knew of was the one included at Razib's post. Notice that B006 has two sub-haplotypes and that the greatest diversity is in Asia, not where it's most common.

    Anyhow neither Australians nor South Asians had been sampled then and many less Africans too.

    "It's safe to claim neanderthal ancestry, or could it be descended from an archaic African population who left Africa earlier than other migrations?"

    It's safer than before but there is still some decent uncertainty because of how badly is the Neanderthal sequence (Vindija combo?) known in the details.

    "I read that this haplotype shows a colascence time with all other haplotypes much younger than what's expected for it's neanderthal origins (about 100-200K)".

    Good observation. While I would not pay normally much attention to age estimates, the difference between the given dates and the likely species divergence is striking to say the least.

    But the real substance is in the sequence where B006 and the Neanderthal known sequence are identical (however there's more than half the sequence not known in Neanderthals). There's a figure by the end of the paper with the exact sequence comparison.

    I'd say that the likelihood of this lineage being from, ultimately, a Neanderthal person (can be either gender) is now pretty good. Specially knowing that there is other evidence supporting minor Neanderthal adimixture.

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  3. It's intriguing that this haplotype has a frequency of 9% among non-Africans, because the overall genome is only 1-4% of neandertal origin.
    Apparently the % among non-Africans varies a lot, which might be due to founder effects.

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  4. B006 shows the lowest diversity - so, given its lack of much presence (other than what can easily be explained with late into-Africa migrations) in Africa, this seems like a slam-dunk. However, I would also like to see the remaining phenotypes, and also a wider stretch than what is published in the paper (barely enough to construct a tree).

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  5. shows the lowest diversity

    sorry, I meant least derived.

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  6. ML: 9% looks a bit too high, right? Specially when it's almost non-existent in Asia (except India). It is abnormally high among some Native Americans (and per previous data also Basques and some Mongols) but 9% can only come from not weighting the samples against the populations they actually represent (so Native Americans are overweighted while Asians in general are underweighted).

    I would say that frequency by population has to do with founder effects and random drift, rather than actual Neanderthal admixture, which does not seem to correlate with this lineage at all.

    However I do see some correlation of B006 and Y-DNA P (R and Q). Only this lineage makes a link between South Asia, Europe and Native Americans, right?

    Eurologist: the lineage was reported to exist previously (just more or less forgotten eventually). Here there is a link, though there was another paper a few years(?) later that I cannot locate now.

    This paper just shows that B006 could well be the Vindija (Neanderthal) X-DNA lineage. However, as the Neanderthal sequence is quite incomplete, they cannot be sure.

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  7. "However I do see some correlation of B006 and Y-DNA P (R and Q). Only this lineage makes a link between South Asia, Europe and Native Americans, right?"

    Yes, but it's also found in Australia and it's absent in many Native American populations, as well as in some Europeans. It's also present en North Africa, where there aren't too many R and Q lineages as far as I know, and neanderthals don't have any special relationship with these lineages.

    "However, as the Neanderthal sequence is quite incomplete, they cannot be sure."

    The genome of an entire species can't be complete with only 3 individuals as it's the case. Fortunately many other neanderthal genomes are being decoded or will be decoded in the near future. I suspect many more confident information will be raised by then, but I thought they decoded the "complete" neanderthal genome, or at least that was what I understood.

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  8. I tried to look for table S1 but I cannot find it, so I'm a bit amiss on how exactly each population is relevant.

    Still I do find affinity (not strict identity) with Y-DNA P. An Y-DNA affinity for an X lineage is rather unstable in any case because each time the X chromosome is in a male generation, it requires of a female one after it in order to transmit it. However X imbalance towards the European clades was found in Americans ("Mestizos" from Colombia?), supporting repeated arrivals of males from Europe but a stable locally rooted female ancestry, each generation more European.

    "The genome of an entire species can't be complete with only 3 individuals as it's the case".

    It's a problem of the sequences not the genetic pool. A single individual is enough for a complete sequence in principle but in the Neanderthal case it was a very damaged DNA. Instead the Denisova finger's DNA was almost intact (maybe it froze?)

    "but I thought they decoded the "complete" neanderthal genome, or at least that was what I understood".

    They reached a resolution of only some 60% AFAIK. Not "complete" yet but complete enough to compare.

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  9. "I tried to look for table S1 but I cannot find it, so I'm a bit amiss on how exactly each population is relevant. "

    I also cannot find that table anywhere. Does the article have any supplementary info?

    "They reached a resolution of only some 60% AFAIK. Not "complete" yet but complete enough to compare."

    Yes, but this has nothing to do with damage. Carles Lalueza explained it, and said that this has something to do with repeated sequences (I'm not a geneticist, so I wasn't able to understand well).

    I think the overall results are quite consistent despite the damage. I mean, the list of unique genes to us match quite well some differences we can see looking at their skeletons, for example, one gene called RUNX, another gene related with smelling, etc.

    With only three individual genomes it's quite difficult to generalize for all neanderthals, because for example, neanderthals from the Levant were quite different. The genome comes mainly from three women who lived in eastern Europe, the contribution from El Sidrón, for example, was of 0,1 % which is very low.

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  10. I do understand that the Nenaderthal genome is incomplete because of bacterial damage. It could have been improved up to 80%? Maybe but its low coverage is still because of damage, mostly.

    Obviously the Neanderthal genome is lacking in more than 50% of the sites in this particular region.

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  11. "I do understand that the Nenaderthal genome is incomplete because of bacterial damage. It could have been improved up to 80%? Maybe but its low coverage is still because of damage, mostly."

    Well, you should ask to a geneticist who participated in the project, because I can't answer you, but when I asked to Lalueza why they finished having only a 63%, he told me it was more than enough.

    At first, the DNA found in the neanderthal cells was more than 95% bacterial, it had to be "purified" with DNA techniques. This is why the project has received so many criticism; for example, see this paper:

    http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.0030175

    but fortunately the damage could be addressed well, so the results are quite confident, I understand.

    "Obviously the Neanderthal genome is lacking in more than 50% of the sites in this particular region."

    Are you talking about B006 or chromosome X?

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  12. I'm talking about the pseudo-haploid zone of the X chromosome, where the haplotype is analyzed. See table 1.

    Still it is 16 sites missing out of 36, so less than 50%. It's 50% of those sites that include transitions towards B006 (2/4).

    Whatever the case it's not like the 40% missing in the Neanderthal genome is trivial and this is a clear example.

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  13. "I'm talking about the pseudo-haploid zone of the X chromosome, where the haplotype is analyzed. See table 1.

    Still it is 16 sites missing out of 36, so less than 50%. It's 50% of those sites that include transitions towards B006 (2/4). "

    Ah I see... :(

    Unfortunately many sequences are missing, but there's enough for that study and others to compare neanderthal DNA with that of living people. I suspect many other neanderthal DNAs are being sequenced, so maybe in the near future we'll be able to cover these missing sites. In the case of microcephalin, an Italian neanderthal was analyzed and the authors found that it had ancestral microcephalin. I don't know if the nuclear DNA from el Sidrón it's in better conditions to be analyzed, but in any case science is discovering more and better methods to analyze ancient DNA.

    Until then, we have a lot of information from neanderthals with that 60%, and many other studies like that, finding common haplotypes between living people and neanderthals are expected to come soon.

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  14. "Whatever the case it's not like the 40% missing in the Neanderthal genome is trivial and this is a clear example."

    I'm not able to understand what's being said here, sorry :(

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  15. Just meant that the 40% of Neanderthal DNA that we do not know would be still useful to know: it's not just DNA that is all the same in all people but stuff that does change.

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