Back to work

My apologies to readers for being for so long in "lazy mode". Actually I got interrupted largely by a request to provide a quality article on Basque, Sardinian and European origins for a soon to be published collective book in Basque language. This took me a lot of time and energies in late March and early April, so basically I put everything else on hold. The last weeks I've been resting indeed, what may be aggravated by a declining health that makes me sleep irregularly and often for much longer than most of you do. Being fed up with Internet information feeds and a quite active political reality also drain my energies to other endeavors, not to mention paperwork.

In this sense I want to announce that I have begun recently a new multi-purpose blog in Spanish language: Bagauda. Most of it is politics, I warn you, but I have also included the unedited raw article for that book I mention in the previous paragraph (prior to translation to Basque and corrections). I'm reasonably sure that those of you who have Spanish as primary or even secondary language will be interested in having a look (→ here).

Another relevant entry was the announcement of the upcoming congress on Iruña-Veleia to be held on May 7 in Vitoria-Gasteiz. You can still register but hurry up.

I will now proceed to comment in a separate entry on the news of the week, the Fu et al. study of a large array of Paleoeuropean ancient DNA. But, before I get to that, I must mention some interesting studies that I have not been able to get time to even properly read, let alone discuss:

• K. Voskarides, S. Mazières et al., Y-chromosome phylogeographic analysis of the Greek-Cypriot population reveals elements consistent with Neolithic and Bronze Age settlements. Investigative Genetics 2016. Open access → LINK [doi:10.1186/s13323-016-0032-8]
• B. Vernot et al., Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science 2016. Freely accessible (with registration?) → LINK [doi:10.1126/science.aad9416]
• Y.Y. Waldman, A. Biddanda et al., The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry. PLoS ONE 2016. Open access → LINK [doi: 10.1371/journal.pone.0152056]

Another intriguing new independent paper by a regular visitor and commenter to this blog, Olympus Mons, that I have not yet read is:

→ R1b from Sulaweri-Shomu to Bell Beaker, available as PDF or in blog format.

He seems to argue for a Caucasus origin of both the lineage and Bell Beaker phenomenon. I have no opinion as of yet, because, simply put, I have not been able to read it in full.

Another regular visitor here to have put an independent paper online, also on the issue of R1b origins, is Paul Conroy:

→ Anatole A. Klyosov and Paul M. Conroy, Origins of the Irish, Scottish, Welsh and English R1b-M222 population. Available at Paul's Academia.edu account.

Again I have not yet got the opportunity to read it, so no opinion. 

Feel free to use this entry to comment on any of the aforementioned studies or articles or to provide info about stuff I may have missed.

H. heidelbergensis is Neanderthal ancestor and not 'Denisovan' cousin

Quickies

The unprecedented sequencing of a small fraction of the autosomal DNA of Homo heidelbergensis from the Sima de los Huesos of Atapuerca proves that they are in direct ancestral line to H. neanderthalensis and not particularly related to Denisovans.

Matthias Meyer et al., Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins. Nature 2015. Pay per view → LINK [doi:10.1038/nature17405]

Abstract

A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago¹. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals². However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.

Some articles that describe the findings:

→ at Nature News

→ at Público (in Spanish)

Matthieson also found that the Sima de los Huesos hominids were closer to Denisovans and Neanderthals in mtDNA two years ago. But this sequencing of their nuclear DNA puts them much closer to Neanderthals instead.

Prüffer et al. found in 2013 that Neanderthals form a cline with "Denisovans" in nuclear DNA but not in mtDNA, in which they are closer to us. This one is a very interesting read for background, as it explores in great detail the various possible scenarios.

That "Denisovans" could be closely related to H. erectus (a catch-all term for most archaic populations, particularly in Asia) has been considered as very possible before (Waddell et al. 2012) but there is no genetic confirmation so far, neither strong rejection. Getting DNA from such ancient specimens is considered a breakthrough and this partial sequencing of 400,000 years ago is believed to be within the very limits of absolute possibility.

[Conclusions edited on Mar 19th because I got it all wrong and don't wish to keep confusing anybody else. Instead I listed several relevant background studies, judge yourself].

>100 Ka old tools found in Sulawesi

Quickies

Flake type tools dated to approx. 118,000 years ago have been found in Sulawesi (Indonesia). They imply that some species of human was making them but it is unclear which one. Homo floresiensis (alias The Hobbit) is maybe the first one that comes to mind but actually there are other possibilities: on one hand the significant H. heidelbergensis (alias Denisovan) admixture found in Australasian aboriginals would be consistent with its presence somewhere in SE Asia, Wallacea even, but another serious possibility is that they are in fact made by H. sapiens, whose presence in other parts of Asia soon after this date (or even before in the case of West Asia) is well known by now.

Good documentaries on human Prehistory

I just watched the documentary "First Peoples - Asia" (by NOVA) and found it quite good, discussing many of the issues that I and the readers of this blog have been following and discussing the last years on the settling of Asia (and geographical dependencies): the Zhirendong jaw, the Nubian points of Arabia, the archaic admixture events... 

The only issue is that for some odd reason (copyright masking?) interviewed people voices often have a too high pitch.

I hope the other four documentaries of the series are similarly good. I haven't watched them yet but the full playlist is embedded below beginning with the Asian colonization movie. For many readers it won't be that interesting personally (they already know all or most of it, maybe even better than what the movie explains) but it is still a promising tool to share your hobby with family and friends, so watch it in good company. 

Enjoy!

Update (Jan 9):

I've watched already four of them (Africa, Asia, Australia and Europe) and the European one is no doubt the worst: a superficial Neanderthal hybridization neo-myth spearheaded by John Hawks. Also the only map or description of the route followed by modern humans to Europe is absolute nonsense: directly from Africa via Palestine, when in fact it's extremely clear that at least most of the lineages went all the way to SE Asia and back before ever entering Europe. What happened to the spear in the rib of Zawi Chemi Shanidar man? What happened to the very fast replacement in the early Aurignacian, coincident with the Campanian Ignimbrite eruption? What about dogs? Not a word! Just whitewashing of the probably quite violent Sapiens-Neanderthal interaction. You can skip that one, really, it's pretty much nonsense.

Some hyper-hybridationism permeates all the documentaries but the others seem much better: the Asia one is quite good, the Africa one is not bad either (although could be much better if they paid more attention to archaeology, also Africa deserves 50% of the documentary space probably), the Australia one is OK but it simply ignores Papua and Wallacea altogether, what is a bit perplexing to say the least. The Europe one is just horrible: it has some facts but half of it its John Hawks' preaching his particular ideology about people being oh-so-nice that they probably used spears as toothpicks, Paabo making a lot of extra work for the cleaning crew (spectacular admittedly but should be in a separate Neanderthal docu, not in one dedicated to H. sapiens) and some real archaeology scattered around (but definitely not enough at all).

Altitude-adaption in Tibetans is "Denisovan-like"

It seems that archaic humans left a small but critical legacy among us:

Emilia Huerta Sánchez et al., Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 2014. Pay per view → LINK [doi:10.1038/nature13408] 

Abstract

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau^{1, 2, 3}. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans^{4, 5, 6, 7, 8, 9, 10}, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.

Figure 3: A haplotype network based on the number of pairwise differences between the 40 most common haplotypes.
The haplotypes were defined from all the SNPs present in the combined 1000 Genomes and Tibetan samples: 515 SNPs in total within the 32.7-kb EPAS1 region. The Denisovan haplotypes were added to the set of the common haplotypes. The R software package pegas²³ was used to generate the figure, using pairwise differences as distances. Each pie chart represents one unique haplotype, labelled with Roman numerals, and the radius of the pie chart is proportional to the log₂(number of chromosomes with that haplotype) plus a minimum size so that it is easier to see the Denisovan haplotype. The sections in the pie provide the breakdown of the haplotype representation amongst populations. The width of the edges is proportional to the number of pairwise differences between the joined haplotypes; the thinnest edge represents a difference of one mutation. The legend shows all the possible haplotypes among these populations. The numbers (1, 9, 35 and 40) next to an edge (the line connecting two haplotypes) in the bottom right are the number of pairwise differences between the corresponding haplotypes. We added an edge afterwards between the Tibetan haplotype XXXIII and its closest non-Denisovan haplotype (XXI) to indicate its divergence from the other modern human groups. Extended Data Fig. 5a contains all the pairwise differences between the haplotypes presented in this figure. ASW, African Americans from the south western United States; CEU, Utah residents with northern and western European ancestry; GBR, British; FIN, Finnish; JPT, Japanese; LWK, Luhya; CHS, southern Han Chinese; CHB, Han Chinese from Beijing; MXL, Mexican; PUR, Puerto Rican; CLM, Colombian; TSI, Toscani; YRI, Yoruban. Where there is only one line within a pie chart, this indicates that only one population contains the haplotype.

See also this entry on Neanderthal introgression being subject to positive and negative selection.

Neanderthals, Denisovans and everything else

A recent analysis of the nuclear DNA of a Neanderthal toe from Altai has caused widespread interest.

Kay Prüffer et al., The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 2013. Pay per view → LINK [doi:10.1038/nature12886]

The story of a finger and a toe

Both the Denisovan and Neanderthal DNA sequences discussed in this paper come from small bones found at the same location: Denisova cave, Altai Republic. The Denisovan sequence that revolutionized human paleogenetics a few years ago corresponds to a finger phalanx bone of some 50,000 years ago. The less notorious Neanderthal sequence discussed in this study corresponds to a toe imal phalanx, which was found in a lower layer in the same gallery of the same cave, and hence should be older.

This is very interesting to underscore because it seems to imply that Neanderthals were in Altai and specifically in Denisova cave very early, at dates similar to those we find in West Asia (Tabun excepted) and they may even be older than Denisovans in the very cave that gave them their name.

The toe sequence was found in a previous study to have Neanderthal mtDNA, closely related to the lineages of European Neanderthals of various dates and sites. Instead the finger mtDNA (Denisovan) was derived from a more ancient branch of humankind than the very point of split between Neanderthals and modern humans (H. sapiens) and has been recently shown to be related to European H. heidelbergensis from Atapuerca. 

Notes in red are mine.

This study focuses on the autosomal DNA of both Neanderthals and Denisovans. Unlike mtDNA, whose phylogenetic position is simple and quite straightforward, autosomal or nuclear DNA (nDNA) is extremely much more complex to understand because of its recombining nature, requiring of statistical approaches, which may get extremely complex and potentially subject to premise biases. When comparing two individuals this gets largely simplified but it is a lot more complex when doing the same with larger samples.

And that is precisely what this study does: comparing one Denisovan, several Neanderthals and also several modern humans. Therefore it is a very complex paper and the authors necessarily assume some evaluation risks, which nevertheless are discussed in depth in the supplemental material, a methodology of the Pääbo team that we can't but greatly appreciate.

Age estimates

The study makes two age estimates, one based on a very conservative and truly unbelievable Pan-Homo split date of 6.5 Ma BP and the other based on observed per generation mutation rates, which happens to be perfectly coincident with a Pan-Homo split of 13 Ma BP, the oldest extreme of Langergraber's estimate. This coincidence alone is of enough relevance for all molecular clock approaches, because it effectively demands the doubling of all age estimates based on the ridiculously short 6.5 Ma Pan-Homo split supposition. 

Red outlines are mine. Click to enlarge.

It also produces a semi-reasonable San-West African age estimate of c. 86-130 Ka, although I would think it a bit older in fact or at the very least at the top end. This highlights the severe difficulties of such molecular clock estimates, because a 4 Ma divergence between the alleged introgressing mystery archaic in the Denisovan genome, seems out of the question according on the archaeological and paleontological record, which only documents Homo species since c. 2 Ma ago, half that time (within the estimate but clearly very far from the top end).

Altai Neanderthal inbreeding

An important finding of this study is that the studied individual was extremely inbred, with parents in effective relationship comparable to that of grandparent and grandchild or half siblings. This inbreeding tendency, even if extreme, is not so strange in populations that have experienced founder effect bottlenecks and small population sizes. The Denisovan and the modern human Karitiana people are not so extreme but range in the lower end of double first cousins level of genetic relationship between the parents. Other Native Americans like the Mixe are close to that range, while the other compared populations, Papuans and Sardinians, show much lower levels of inbreeding.

Whatever we may think of Altai Neanderthal inbreeding, their drift parameter is still very low when compared with European Neanderthals. This is not discussed in the paper but such extreme drift also seems to imply extreme inbreeding issues in European Neanderthals, even if these may have other causes such as an extremely strong founder effect or whatever.

Bonobo-specific segments were removed, so the bonobo position is not realistic.

Inferred population history

Both populations leading to the Altai Neanderthal and Denisovans, but not modern humans, appear to have gone through a strong decline in population size since hundreds of millennia ago. The Denisovan decline seems to begin c. 800 Ka ago while the Neanderthal one may have begun c. 500 Ka ago. While this is coincident with a general expansion of the H. sapiens branch (still undifferentiated in Africa), peaking around c. 250 Ka ago before differentiation and relative decline. In their words:

All genomes analysed show evidence of a reduction in population size that occurred sometime before 1.0 million years ago. Subsequently, the population ancestral to present-day humans increased in size,whereas the Altai and Denisovan ancestral populations decreased further in size. It is thus clear that the demographic histories of both archaic populations differ substantially from that of present-day humans.

Neanderthal and Denisovan admixture in modern humans

The new tests confirm in essence the previous findings: there is significant Neanderthal introgression in modern humans descending from the migrants out of Africa and there is also significant Denisovan one among Australasian populations.

Additionally and with some caution, the authors think that much lesser Denisovan introgression (of around 0.2%) is found among East Asians and that these, as well as Native Americans, show slightly more Neanderthal admixture than West Eurasians. In my understanding this may be caused by minor African flow to West Eurasia after the admixture event (and/or residual "First Arabian" persistence) and I would think that measuring South Asians would help to clarify this issue (because African admixture is negligible in the subcontinent but they are also distinct from East Asians).

These measurements are so weak that the authors agree to all kind of cautions about them in any case.

In addition to all this, the supplemental material (section 13) also detects tiny, almost homeopathic, amounts of Neanderthal gene flow to Yorubas (~0.02%), obviously mediated by H. sapiens backflow from Asia and Europe into parts of Africa, which eventually influenced other African populations. An even more diluted amount may also be present among the Mbuti Pygmies.



Altai Neanderthal admixture in Denisovans

This issue is not really explained in the paper as such, and we have to reach out to the Supplemental Information chapter 15 in order to grasp it.

It is clear that the Altai Neanderthals are closer to Denisovans than other Neanderthals are by approx. the following fractions (directly deduced from the raw affinities listed in fig. S6a.2):

• 2% more than Mezhmaiskaya
• 7% more than Vindija (avg.)
• 9% more than El Sidrón

Feldhofer appears closer instead but this sequence was not used by the authors in most tests because it has too dubious quality.

In section 15 of the supplementary material, using complex methodology and lamenting the lack of a second Denisovan sample which would be most useful, they estimate a minimal 0.5% (Altai) Neanderthal introgression in Denisovans, with strong warnings that this could well be quite higher. I don't know why they are not even considering a more direct approach, but I would dare to guesstimate the introgression to be close to 8% from the above raw data, assuming that there are no further complexities at play, such as other Heidelbergensis introgression in European Neanderthals, etc. The drift parameter (see above) does not seem to be one such complexity because Mezhmaiskaya is almost as drifted as Vindija yet it is consistently much closer, as it seems to correspond to its specific relatedness to Altai Neanderthals in mtDNA (and possibly also in nDNA if it is admixture what causes their pseudo-tree positioning closer to the root, what would be typical).

Note in blue is mine.

Mystery archaic genetic flow into Denisovans

The authors find that some 0.5-8% of the Denisovan genome appears to come from another hominin, which split from the human trunk even earlier.

We caution that these analyses make several simplifying assumptions. Despite these limitations, we show that the Denisova genome harbors a component that derives from a population that lived before the separation of Neanderthals, Denisovans and modern humans. This component may be present due to gene flow, or to a more complex population history such as ancient population structure maintaining a larger proportion of ancestral alleles in the ancestors of Denisovans over hundreds of thousands of years.

Later in the discussion section they ponder further the implications of this finding:

The evidence suggestive of gene flow into Denisovans from an unknown hominin is interesting. The estimated age of 0.9 to 4 million years for the population split of this unknown hominin from the modern human lineage is compatible with a model where this unknown hominin contributed its mtDNA to Denisovans since the Denisovan mtDNA diverged from the mtDNA of the other hominins about 0.7–1.3 million years ago⁴¹. The estimated population split time is also compatible with the possibility that this unknown hominin was what is known from the fossil record as Homo erectus. This group started to spread out of Africa around 1.8 million years ago⁴², but Asian and African H. erectus populations may have become finally separated only about one million years ago⁴³. However, further work is necessary to establish if and how this gene flow event occurred.

Going to the detail of the matter (i.e. supplemental material sections 16a and 16b), one of the key details is that present-day Africans share more derived alleles with Neanderthals than with Denisovans. This can only be explained because Denisovans have other archaic ancestry prior to their apparent divergence from Neanderthals or (what is about the same) because Denisovans diverged themselves prior to the Neanderthal-Sapiens split, what is what the mtDNA (unlike the nDNA) suggests. However the difference, even if consistent across comparisons, is too small (a few percentage points) to be attributed to the later scenario.

This means that Denisovans appear to be at nDNA level some sort of an independent branch of proto-Neanderthals with some other but minor archaic admixture. Instead at mtDNA level they appear to be unrelated to Neanderthals and related instead to H. heidelbergensis (a detail not discussed in this paper because it is a too recent independent discovery).

There are still many details to explore but, in principle, it would seem that the Denisovan branch appears to be a divergent proto-Neanderthal one (maybe related to the Hathnora hominin, which looks very much Neanderthal) with lesser other archaic (H. heidelbergensis?) admixture, which nevertheless remained prominent in their mtDNA for whatever accidental reason.

Whether the H. heidelbergensis population of Atapuerca responds to this same profile (i.e. they were Denisovans too) or belongs instead to the "other archaic" population which introgressed in the Denisovan genome remains to be solved. So far we only know the mitochondrial lineage and this one may be misleading, as seems to be the case with the Denisova hominin.

Note in red is mine

Modern human genetic evolution

Benefiting from the high quality of the archaic genomes of Altai, the authors cataloged a long list of simple mutations exclusive to our species: 31,389 single nucleotide substitutions and 4,113 short insertions and deletions (indels). Additionally they found other 105,757 substitutions and 3,900 indels shared by 90% of their modern human sample of 1094 individuals.

They suggest some lines for future research in this regard, maybe focusing on genes known to influence brain development or regions that could show signs of positive selection. These preliminary lines of research are explored in SI-20, noticing potential selection in genes that affect the ventricular zone of the brain and cell proliferation in fetal brain development.

The Denisovans were not alone

H. heidelbergensis from Atapuerca
Cranium 5 "Miguelón"
(CC by José Manuel Benito)

About half an hour ago, somewhat cryptic comments in this blog and my email woke me up, more abruptly than I would have desired maybe, to a new game-breaking finding: researchers have sequenced the mtDNA of a 400,000 years old Homo heidelbergensis from Atapuerca (Iberian Peninsula, Europe) and it was not at all like most would have expected.

Mathhias Mayer et al., A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature 2013. Pay per view → LINK [doi:10.1038/nature12788]

Abstract

Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene¹. One of these sites, the ‘Sima de los Huesos’ (‘pit of bones’), has yielded the world’s largest assemblage of Middle Pleistocene hominin fossils^{2, 3}, consisting of at least 28 individuals⁴ dated to over 300,000 years ago⁵. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits^{6, 7, 8}. Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans^{9, 10}, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.

The key figure is this one, which phylogenetically relates the newly sequenced mtDNA with the known Homo ones:

Figure 4: Bayesian phylogenetic tree of hominin mitochondrial relationships based on the Sima de los Huesos mtDNA sequence determined using the inclusive filtering criteria.
All nodes connecting the denoted hominin groups are supported with posterior probability of 1. The tree was rooted using chimpanzee and bonobo mtDNA genomes. The scale bar denotes substitutions per site.

It has been argued by all sides (myself included) that the H. heidelbergensis of Atapuerca and other European locations are ancestral to Neanderthals. Some say that also to H. sapiens, while others argue that ours is a wholly distinct line, derived from H. rhodesiensis, and yet others claim that H. rhodesiensis is not different from H. heidelbergensis in spite of being older and rooted, it seems, in South Africa.

The clear evidence for migrations out of Africa, before our species, is limited to two periods: (1) the c. 1.8 Ma old migration of H. erectus/georgicus with Olduwayan technology (mode 1, "choppers"), and (2) the c. 1 Ma old migration of H. ergaster/antecessor (sometimes also confusingly called H. erectus) with Acheulean technology (mode 2, typically "hand axes"). Archaeological evidence for later migrations does not exist.

See: Late human evolution maps at Leherensuge.

So we could well ask, if H. heidelbergensis is not ancestral to Neanderthals, then where do Neanderthals come from?

It must be answered that we do not know yet if H. heidelbergensis is or not ancestral to Neanderthals or in what degree it is. The mitochodrial (maternal) lineage may well be misleading in this sense. Denisovans themselves were much more related to Neanderthals via autosomal (nuclear) DNA than the mtDNA, so it may also be the case with European Heidelbergensis.

In fact it is still possible that these individuals represent some sort of admixture between older and newer layers of human expansion. But there is no clear answer yet. What is clear is that no Neanderthals have these mitochondrial sequences but others closer to those of H. sapiens - and this is the most puzzling part in fact. 

But one thing is clear: the World is much bigger than just Europe, and that was also the case back in Paleolithic times. Our answer may well lay under the sands of some tropical desert, the waters of the sea or whatever other place in Asia or Africa.

Even if we'd find the "missing link", so to say, we might not be able to discern it as such without genetic sequencing and that is often not even possible at all. However this pioneer research, as well as its precursors on a bear also from Atapuerca and a 700,000 years old horse (the true record of ancient DNA recovery), give us some hope of getting an improved, even if sometimes perplexing, understanding of the complexity of the human adventure.

Nearly complete sequence of a Neanderthal from Altai

A 99.9% complete Neanderthal genome from a toe bone found at Denisova Cave (Altai, Southern Siberia).

Documents at Max Plank Institute for Evolutionary Anthropology, Department of Evolutionary Genetics.

A high-quality Neandertal genome sequence

The genome sequence was generated from a toe bone discovered in Denisova Cave in southern Siberia in 2010. The bone is described in Mednikova (Ethnology & Anthropology of Eurasia 2011. 39: 129-138).

DNA sequences were generated on the Illumina HiSeq platform and constitute an average 50-fold coverage of the genome. 99.9% of the 1.7GB of uniquely mappable DNA sequences in the human genome are covered at least ten times.
Contamination with modern human DNA, estimated from mitochondrial and nuclear DNA sequences, is around 1%.

The figure shows a tree relating this genome to the genomes of Neandertals from Croatia, from Germany and from the Caucasus as well as the Denisovan genome recovered from a finger bone excavated at Deniosva Cave. It shows that this individual is closely related to these other Neandertals. Thus, both Neandertals and Denisovans have inhabited this cave in southern Siberia, presumably at different times. 

One may wonder: how can they know it is a Neanderthal and not a "Denisovan"? Because of the close genetic affinity with other Neanderthals from Europe:

It is still possible, considering its position in the tree that the Altai Neanderthal had minor "Denisovan" admixture. But it would be very minor in any case. 

More Neanderthal admixture details

The main conclusion of this new study seems to be that East Asians have normally more Neanderthal admixture than South or West Eurasians. Also the Maasai from East Africa have been shown to have minor Neanderthal admixture, consistent with the also minor Eurasian genetic component they have.

Jeffrey D. Wall et al., Higher Levels of Neanderthal Ancestry in East Asians Than in Europeans. Genetics 2013. Freely accessible at the time of writing this → LINK [doi: 10.1534/genetics.112.148213]

Abstract

Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from roughly 30-300 thousand years ago (Kya). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 Kya. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations.

There is a sentence in page 8 in which the authors claim that:

By using the high coverage Denisova genome, we are able to show that the admixture rate into East Asians is 40% higher than into Europeans.

However I fail to see it in the D-statistic graphs, which show less than 15% more Neanderthal admixture in Eastern Asians than in Europeans (on average and discounting error margins, which strongly overlap). It may be therefore another case of hair-splitting.

Instead the evidence of weak Neanderthal admixture (via minor Eurasian  genetic influence) in the Maasai of East Africa seems more solid: while error margins of Maasai and Luhya do overlap, the main blocs do not.

Figure 3. Summary of significance tests for average values of D. Positive values indicate that the second sequence is more similar to the Neanderthal genome than the first sequence. In all parts, the box plots indicate the range of D values obtained for pairs of individuals from the populations indicated. Parts A and B are box plots of individual D statistics computed for each individual from the specified population compared with each Yoruban. The p values are from the randomization test, Test 1, of significant differences in the average D values for different pairs of populations. Parts C and D show box plots of individual D statistics computed for every pair of individuals in the specified populations. The p values are from the randomization test, Test 2, of significant differences of the average D from 0. See also Table 2.

It is surely convenient to look carefully at all the data, including the supplementary materials, before jumping to any strong conclusions. Among them I found more interesting fig. S1:

Figure S1: Box plot of the D-statistics for Analyses A and B for the set (Afr, X), where X was any of the non-African populations, CEU or TSI (Europeans, green), CHB or JPT (East Asians, blue), or GIH (South Asian, pink) (PDF, 222 KB).

As we can see here, the error margins continue overlapping very strongly, but, assuming that we can jump to conclusions based on the norm (thick black line), which is assuming some risks indeed but also the only way to (tentatively) agree with the authors' conclusion of greater Neanderthal admixture among East Asians, then the causes should be:

1. Founder effect among East Asians, known to have less overall genetic diversity and suspected to have undergone some extra (mild?) bottleneck at their ancient origins.
2. Low-level African (and surely also early OoA residuals from West Asia) admixture among West Eurasians, notably Tuscans (TSI) in these samples but also to some extent all Europeans (incl. CEU). This has the effect of increasing genetic diversity but also of slightly diluting Neanderthal admixture. The control here are Indians (GIH), which show slightly more Neanderthal admixture than Europeans (but are still closer to these than to East Asians also in this aspect).

Indians (who don't seem to have any post-OoA African admixture, unlike Europeans and West Asians, who have it at variable low levels) suggest that factor #2 (dilution) weights only somewhat and therefore that factor #1 (East Asian founder effect) must be considered the main one instead. 

But, unless someone can point me where I am wrong, I fail to see neither the alleged 40% excess Neanderthal admixture in Orientals nor why would these results question the single admixture episode (or period) at the origins of migration out of Africa (OoA).

To finish this entry, it must be mentioned that the authors could only detect at most the tiniest fraction of Denisovan admixture among the sampled populations (i.e. nothing relevant and with no regional differences). However they did not research, admittedly, the South China populations suggested to have slight more Denisovan input by  Skoglund and Jakobsson 2011.

See also:

• On some details of the Neanderthal genome draft (Leherensuge 2010, when I noticed that Chinese, but not Japanese, samples looked like having slightly more admixture)
• Splitting hairs on the Neanderthal affinity, questioning if the slight greater Neanderthal admixture detected by John Hawks among Europeans (the opposite of what is claimed here) was actually meaningful at all.
• East Asians now claimed to be more Neanderthal than Europeans (prelude of this paper in a sense)
• Intriguing North African Neanderthal admixture paper

Tianyuan, mtDNA B and the formation of Far Eastern peoples

The genetic study of the ancient man of Tianyuan is already online, as I commented yesterday in a quick update.

Qiaomei Fu et al., DNA analysis of an early modern human from Tianyuan Cave, China. PNAS 2013. Open access → LINK [doi: 10.1073/pnas.1221359110]

Abstract

Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia.

Mitochondrial DNA

Part of fig. 1

And the old guy (or is it a woman?) happened to carry the matrilineage (mtDNA) B, more specifically B4'5, defined by a relatively long deleted block at positions 8281-8289 (this excludes B6 now linked with R11 and also the other relative of all them R24, see PhyloTree for details). However within B4'5 the lineage could not further be resolved within the modern haplogroups, so it is neither B4 nor B5 but a third branch of the same haplogroup. 

The authors actually talk of "haplogroup B" but they explicitly mention a deletion of a 9-bp motif (5′-CCCCCTCTA-3′, revised Cambridge reference sequence positions 8,281–8,289) as well as a substitution at position 16,189, what makes it unmistakable B4'5 per the current PhyloTree build.

The tree to the right illustrates this fact, placing Tianyuan man's lineage hanging directly from the root of this haplogroup that, beyond reasonable doubt, coalesced somewhere in East Asia (probably SE Asia, with Laos and Hainan being good references judging on diversity) some time before this person lived and died near what today is Beijing. 

What does it tell us? Really nothing new, at least within the parameters I have been managing: it confirms that the expansion of mtDNA B4'5 was already happening back in that time and that it had reached more or less its current area of expansion in East Asia (American and Oceanian B variants expanded later, of course). It also implies that its ancestors R and N, which experienced important successive expansions in the course of the colonization of Eurasia by our species had expanded  at an even earlier date (again nothing new to me but a nice confirmation anyhow).

On the other hand, this person's particular matrilineage went eventually extinct later on. This again does not tell us too much because it is something to expect with the course of time, especially at low population densities, as was the case in the Paleolithic. He can still be ancestral to modern peoples in the area and elsewhere but not by a purely mother-to-daughter line - at least not that we know. 

Chromosome 21 autosomal DNA

Because of the poor state of the DNA, the researchers had a difficult time sequencing it (technical details in the paper), however they managed to reconstruct a good deal of chromosome 21, which they used to compare with modern humans and also with Neanderthals and the so-called Denisovans. 

The result places Tianyuan closer to modern Far Eastern populations than to the rest of modern humans. This clearly indicates that the process of division in various more or less homogeneous subcontinental-sized populations was already somewhat advanced. 

Fig. 2. Maximum-likelihood tree relating the chromosome 21 sequences of the Tianyuan individual, 11 present-day humans, and the Denisovan genome. The most strongly supported gene-flow event is shown in yellow. Bootstrap support for all internal edges is 100% except for the edge putting Tianyuan outside the four Asians, which is 31%. The scale bar shows 10 times the average standard error of the entries in the covariance matrix.

While it is generally acknowledged that Papuans cluster at very deep level with East Asians, the authors are not fully persuaded of the exactitude of this tree, particularly in this aspect. They declare:

We note, however, that the relationship of the Tianyuan and Papuan individuals is not resolved (bootstrap support 31%). Further work is necessary to clarify whether this reflects the age of the Tianyuan individual relative to the divergence between modern human populations.

The caveat is particularly relevant because the colonization of New Guinea is at least as old as 49,000 years ago, some ten millennia before Tianyuan, what does not fit too well with the tree at that level of detail, assuming (as I do) that modern Papuans are direct unmixed descendants of those early settlers. Papuans do carry at high frequencies a related matrilineage (P also basal descendant from R) but that is also true of modern Europeans and they appear more distant in the tree above.

A good contrast to understand better the difficulties in getting a good picture from autosomal DNA, especially one so old, is table 1:

Here we can appreciate the differences and proximities by another measure. The closest compared modern person to Tianyuan man is a Karitiana, followed closely by the Han and, surprisingly, by the Sardinian and the French, and only then the Dai and Papuan. 

The distance of the Karitiana to Tianyuan man is still greater than that with not just the Han or the Dai but also the Europeans. However this can be argued to be because Native Americans must have a deep dual East Asian and West Eurasian origin, the latter via Altai (Y-DNA Q, mtDNA X2).

Let's check the Han then, who are not believed to have any meaningful West Eurasian admixture. Curiously the paradox happens again: the Han is somewhat closer to Europeans by this measure than to Tianyuan, and even their comparison with the Papuan shows up slightly less differentiated. 

This is admittedly harder to explain but we can conclude that either (a) this method can only grasp affinity/divergence to some degree or (b) that the Tianyuan partial genome indicates a very preliminary level of continental differentiation. Or (c) both. Of course time is the main cause of genetic differentiation and by no means we can imagine that such an ancient individual would be too similar to his modern plausible descendants but, on the other hand, all (including Tianyuan mtDNA) indicates that the process of continental differentiation was already well developed 40,000 years ago (most European ancestry must come from people living in Europe or West Asia back then) so we can either blame subtle flows like Siberian migrations that have kept both genetic pools somewhat closer than in pure isolation or we must assume that the measure is not too exact.

Admixture with other human species

The paper also deals with Denisovan and Neanderthal admixture, finding that Tianyuan man was within the modern range for both parameters in East Asia. 

This is very important because it ratifies the mainstream model of two minor admixture episodes: (1) with Neanderthals at the exit from Africa and prior to the Great Eurasian Expansion (so all non-Africans, including Tianyuan man, have very similar levels of Neanderthal admixture today) and (2) with a relative of Denisovans (Homo erectus?) maybe in Indonesia affecting only (or almost only) the aboriginal peoples of Oceania (and Filipino Negritos but not the other so-called Negritos from Malaysia or the Andaman, who are not particularly related anyhow).

(As a side note notice that the Denisovan-like gene flow into Papuans in fig. 2 appears to hang not from the end of the branch but from a very high position, suggesting it was a relative and not the known Denisovans of Altai themselves who became admixed into Papuans and other Oceanian populations, probably a relative living in the route to Australasia).


Update: Marnie just published a mention of a previous work on Tianyuan 1, which focuses on the isotopic evidence for a fish-based diet. 

Ancient North Chinese from 40,000 years ago closely related to modern locals

The information is sketchy as of now but the news in the press indicate that , near Beijing, whose fragmented remains were discovered in 2003, was closely related to modern East Asians and Native Americans.  

The paper is not yet online but the information released to the media strongly suggests that East Asians were already distinct from other populations some 40,000 years ago. This would seem to be based on the sequencing of the mitochondrial DNA and the explicit mention of Native Americans indicates that the lineage must be A, B, C or D (X, the fifth and less common matrilineage of Native Americans, is not found in East Asians, with some exceptions from Siberia, so we can exclude it safely). 

Ancient DNA from cell nuclei and maternally inherited mitochondria indicates that this individual belonged to a population that eventually gave rise to many present-day Asians and Native Americans, says a team led by Qiaomei Fu and Svante Pääbo, evolutionary geneticists at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. 

This would seem to discard some adventurous hypothesis floating around about tremendous demographic changes in the Paleolithic and afterwards, at least for this region. Probably not even when "mode 4" technology arrived to the region (from Altai) c. 30,000 years ago. 

In other words: the seeds of modern populations were already there c. 40,000 years ago in East Asia (and surely also in most other regions) and, even if they may have changed somewhat, they have remained the same at least to some notable degree.

Furthermore, the autosomal DNA also seems to have been sequenced to at least some degree because the researchers state that Denisovan and Neanderthal genetic inputs are at the same levels as modern North Chinese (i.e. some 0% and 2.5% respectively):

The partial skeleton, unearthed in Tianyuan Cave near Beijing in 2003, carries roughly the same small proportions of Neandertal and Denisovan genes as living Asians do (SN: 8/25/12, p. 22), the scientists report online January 21 in the Proceedings of the National Academy of Sciences.

Or in the words of the Max Plank Institute:

The genetic profile reveals that this early modern human was related to the ancestors of many present-day Asians and Native Americans but had already diverged genetically from the ancestors of present-day Europeans. In addition, the Tianyuan individual did not carry a larger proportion of Neanderthal or Denisovan DNA than present-day people in the region.

This also seems to discard models implying Denisovan admixture happening in Siberia or NE Asia and would indirectly support my own hypothesis of admixture with Homo erectus (for which Denisovans, plausibly an Erectus-Neanderthal hybrid, would be just a proxy) in or near Indonesia.

Sources: Science News, Max Plank Institute.


Update (Jan 22): the paper is already online and is open access (cool!)  I don't think I have time to discuss it today but will do tomorrow without doubt (other than the sky falls on my head, you know).

Variation in human (modern and archaic) and chimpanzee lipoprotein APOE

This new study has some interest in understanding some details, of metabolic relevance, of the genetics of humans and our closest relatives:

Annick McIntosh et al., The Apolipoprotein E (APOE) Gene Appears Functionally Monomorphic in Chimpanzees (Pan troglodytes). PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0047760]

Abstract

Background

The human apolipoprotein E (APOE) gene is polymorphic, with three primary alleles (E2, E3, E4) that differ at two key non-synonymous sites. These alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, Alzheimer’s disease risk, and longevity. The relative frequencies of these alleles vary across human populations, and the evolution and maintenance of this diversity is much debated. Previous studies comparing human and chimpanzee APOE sequences found that the chimpanzee sequence is most similar to the human E4 allele, although the resulting chimpanzee protein might function like the protein coded for by the human E3 allele. However, these studies have used sequence data from a single chimpanzee and do not consider whether chimpanzees, like humans, show intra-specific and subspecific variation at this locus.

Methodology and Principal Findings

To examine potential intraspecific variation, we sequenced the APOE gene of 32 chimpanzees. This sample included 20 captive individuals representing the western subspecies (P. troglodytes verus) and 12 wild individuals representing the eastern subspecies (P. t. schweinfurthii). Variation in our resulting sequences was limited to one non-coding, intronic SNP, which showed fixed differences between the two subspecies. We also compared APOE sequences for all available ape genera and fossil hominins. The bonobo APOE protein is identical to that of the chimpanzee, and the Denisovan APOE exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human E4 allele.

Conclusions

We found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.

The relevant details are all in table 1:

Table 1. Variation at key APOE functional sites in Homo and Pan.

There is uncertainty about the correctness of the only known Neanderthal triplet.

Even if E4 seems to be the ancestral type, E3 is the most common allele in our species, ranging from 50% in most populations to as much as 90% among some tribes.

East Asians now claimed to be "more Neanderthal" than Europeans

Unlike what John Hawks had apparently found a few months ago but similar to what I thought apparent from the original Green et al. data back in 2010. 

Mathias Meyer et al., A High-Coverage Genome Sequence from an Archaic Denisovan Individual. Science 2012. Pay per view ··> LINK [doi: 10.1126/science.1224344]

Denisovan ancestry is claimed now to be only found among Aboriginal Australasians (Papuans) but then again the data in the supplementary material (freely accessible) seems, to my untrained eyes, to allow for a thin Denisovan genetic influence in all Eurasia. 

I withhold my judgment because there seems to be a lot of sensibility to methodology in this hair-splitting excercise. John Hawks however has written a lengthy article trying to explain why both results appear contradictory regarding which levels of Neanderthal admixture. I would not bet much for his explanation however: I'd rather suspect that the methodology is not sound enough to estimate very thin admixture, so they are getting contradictory results in the uncertainty zone, what is just logical - even if a Schrödingerian kind of logic, of course.

Another finding is that Denisovans were apparently quite endogamous had very low diversity for modern standards, specially in the short bloc zone (ancient bottleneck) but also in the long bloc one (recent endogamy)*.


___________________________________

*Red text was updated, slashed out text was removed after first publication.

Denisovan and Neanderthal proviral DNA

A provirus is a strand of autosomal DNA that was inserted by a virus once upon a time and got lost in our genome as junk DNA, not being anymore active (would it remain active it'd be a retrovirus). Such insertions are thought to be unique phylogenetic events. 

New research has identified a provirus* (HERV-K-Ne1 = HERV-K-De6, inserted in Chromosome 5) shared by Neanderthals and Denisovans but not Homo sapiens. This is consistent with the previous data that placed their autosomal DNA closer to each other than to Homo sapiens.

Lorenzo Agoni et al., Neandertal and Denisovan retroviruses. Current Biology, 2012. Freely accessible (letter with supplementary material) at the time of writing this.

It must be noted however the mitochondrial DNA, inherited by pure matrilineage, is much closer among our species and Neanderthals than either one with Denisovans, what to me suggest that Denisovans are no new species but a hybrid of Neanderthal and Homo erectus. A theory not yet fully testable for lack of DNA from Asian Homo erectus.

Interestingly Denisovans have also several proviruses not found in Neanderthals, what could well support my theory of hybridization. The detected provirus could hence have migrated from Neanderthals to Denisovans in the hybridization episode (along with lots of other autosomal DNA), while the rest could have been retained from the H. erectus ancestors by the maternal line. 

However as the article is both very technical and succinct, I can't be sure right now of how strongly or weakly can this info support the hybridization model (founded opinions welcome). 

In total the researchers detected three Neanderthal proviruses and 12 Denisovan ones, one of which is shared between both nominal species. It is convenient to remind that while the Denisovan genome was very well preserved and sequenced almost completely, the Neanderthal genome is only known in fragmentary form, amounting to about 60% of the actual genome.

Echoes from the Past (Feb 12)

Some more links for you. 

I'm also lifting the temporary comment moderation filter, hopefully lessons have been learned and no more such measures will be needed. Thanks for your patience.

Prehistory of Europe

Pileta: Más sobre Unas focas pintadas por neandertales podrían ser la primera obra de arte...[es] - Salaman mentions that lack of economic resources do not allow to research further by the moment the possibility that the Nerja seals could have been drawn by Neanderthals. 

Pileta: Catalogan pinturas de Altamira que son 15.000 años más antiguas que los bisontes[es] - Some Altamira paintings are found to be 15,000 years older than the famous bisons. This may make them the oldest rock art in Europe (with permission of Nerja and comparable to Grotte Chauvet). No images of the early Aurignacian art are available yet but it is coincident with a trend to reclassify European rock art as of earlier age and Aurignacian period, as discussed here, but mostly not as early as in this case (before 30 Ka BP).

Neanderfollia[cat] offers us some interesting maps of the MP-UP transition in Europe: 

• Mapa de jaciments Chatelperronians (Chatelperronian sites)
• Mapa de jaciments Aurinyacians (Aurignacian and Proto-Aurignacian, but not Bohunician, sites)

Prehistory of South Asia

AIOC: Lithic continuity & innovation in Holocene South India - D. Fuller introduces a new paper (ppv) on the Holocene industries of India (pictured below).

AIOC: Sourcing the 'lost Saraswati' river: new geological evidence - the same author, discusses how the lost Saraswati river does not match the Holocene geology of the subcontinent but could correspond with that of the Pleistocene.

AIOC: A widening range of textiles on Harappan trading ships

Paleodiet

How to feed a pregnant Neanderthal (AVRPI) - the almost always interesting archaeologist Julien Riel-Salvatore discusses several papers on the apparent myth of high protein Paleolithic diets.

Genetics

Max Planck Institute Leipzig | A High Coverage Denisovan Genome - The Denisovan genome is available for all to explore (the researchers however request courtesy if used for academic publication).

Ultraconserved regions of the genome do not seem to have any particular importance:

PLoS Genetics: Evaluation of the Role of Functional Constraints on the Integrity of an Ultraconserved Region in the Genus Drosophila (open access).

Linguistics

Il tente de décrypter l'ADN de la langue basque (SudOuest)[fr] - Basque cultural journalist Hasier Etxeberria prepares a documentary on the various theories on the origins of the Basque language. 

Psychology and Biology

Brains may be wired for addiction

Preference for fatty foods may have genetic roots

Why do cells age? Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases

Tiny primate 'talks' in ultrasound - our distant Pinoy wild cousin, the tarsier, is not as silent as was thought, they just talk in ways we can't hear.

What elephants want: Ranging and raiding in Asia and Africa | EveryONE  - elephants in fragmented habitats need more land, they also follow the lead of the old ones when raiding crops.