The great panmixia

Human inbreeding has decreased in time through the Holocene:

The history of human inbreeding is controversial. The development of sedentary agricultural societies may have had opposite influences on inbreeding levels. On the one hand, agriculture and food surplus may have diminished inbreeding by increasing population sizes and lowering endogamy, i.e. inbreeding due to population isolation. On the other hand, increased sedentism, as well as the advent of private property may have promoted inbreeding through the emergence of consanguineous marriage customs or via ethnic and caste endogamy. The net impact is unknown, and to date, no systematic study on the temporal frequency of inbreeding in human societies has been conducted. Here we present a new approach for reliable estimation of runs of homozygosity (ROH) in genomes with ≥3x mean coverage across >1 million SNPs, and apply this to 440 ancient Eurasian genomes from the last 15,000 years. We show that the frequency of inbreeding, as measured by ROH, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to endogamy, although singular cases of high consanguinity can also be found in the archaeogenomic record.

I think it is hard to think this is unrelated to decreased pairwise Fst between populations over the Holocene. Fst is a statistic that measures the proportion of genetic variation across two populations in relation to the total variance. In a Pleistocene world of small clans occupying a thinly populated landscape, one can envisage a scenario where gene flow is far more viscous than the more sedentary, but interconnected, world of agriculturalists.

Hunter-gatherers were probably not more xenophobic. Rather, increasing populations by an order of magnitude increases the number of potential geographically close mates a lot.

Another consequence of more gene flow and more partners is that inbreeding also declines, as people have more recent ancestors in their pedigree.

The main caveat I would put into this though is that this applies to dense Eurasian time transects. There is some reason to think that hominins on the northern Eurasian fringe were always on the knife’s edge of sustainability.


Neanderthal Y chromosomes are paleo-modern?

I don’t have time to blog in detail today so I’ll point you to Ann Gibbon’s story, How Neanderthals lost their Y chromosome. You can find the link to the paper in there. The big issue here is that both mtDNA and Y chromosomes were replaced due to introgression from a population closer to modern humans than the Neandersovans, though basal to any modern humans alive today. This new group may actually be basal to the “basal human” group hypothesized by some scholars (there are suggestions of its existence in autosomal admixture into Neanderthals).

The probability of fixation of a newly introduced allele is the frequency of that allele, so how is it that these paleo-modern variants swept into Neanderthals? Perhaps on one locus, but two? One solution offered is naturals selection. This seems plausible, but the possibility of natural selection on Y and mtDNA lineages has always been a “wild card” that would make us rethink a lot of our phylogeography in general.

Finally, though it looks like the vast majority of modern ancestry outside of Africa is derived from a relatively recent (60,000 years ago) rapid expansion, it is clear that the picture at any given time is more complex than the signal we see today. It seems more and more likely that there was more a continuum between the African and Neandersovan lineages, and I strongly suspect that some of the paleo-modern lineages will at some point be detected in some modern groups once we have ancient DNA (the closer genetic distance and low fraction makes it hard for these segments to be identified in extant modern lineages using standard inference).


ABO introgression from Eurasian hominins

One of the oldest group of loci investigated for variation in humans are the ABO antigen markers. There are several reasons for this. First, you can assay them with pre-DNA methods. Second, they vary a lot. Third, they’re very important for things like blood donation.

The fact that they vary a lot means that researchers in the early 20th century used these markers to try and figure out population history. This was not workable for two reasons. First, looking at a locus here and there is not really informative. Y and mtDNA have special characteristics, but even these markers are really informative in a broader context. Second, the ABO locus is subject to natural selection. More precisely, it looks like a lot of immunological markers the ABO locus is subject to balancing selection which keeps it quite diverse.

What does this mean? Basically, variation at any locus is going to turnover. All the polymorphism will “coalesce” back to a common ancestor. The date of coalescence is going to be conditional on parameters such as genetic drift, and selection. Strong sweeps mean all the variance is removed and the coalescence is shallow. Similarly, bottlenecks mean short lifetimes for lineages, since drift cranks away variation. Balancing selection results in the opposite effect. At immunological loci the coalescence is often deeper than the time between the separation of species. The reason is that frequency-dependent selection prevents rare alleles from going extinct (the fitness goes up the rarer the allele).

This is the context of a new preprint, ABO genetic variation in Neanderthals and Denisovans:

Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. As one of the first genetic markers, variation at the ABO gene has been studied for over 60 years, and yet there are some aspects of its evolution that remain mysterious. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We analyze coding variation at the ABO locus from next-generation sequences in ~2,500 individuals from 28 populations, including three Neanderthal and one Denisovan individuals. We use the modern human haplotypes to impute ABO genotypes for the four archaic human genomes. We found that the Siberian Neanderthals, Altai and Chagyrskaya, are both homozygous for a derived Neanderthal variant of the O allele, while the European Neanderthal, Vindija, is a heterozygote for two derived Neanderthal variants, an O variant different from Altai and Chagyrskaya, and a rare cis-AB variant. The Denisovan individual is homozygous for an ancestral variant of the O allele, similar to variants found widely in modern humans. Perhaps more surprisingly, the derived O allele variant found in the Altai Neanderthal can be found at low frequencies in modern European and Southeast Asian individuals, and the derived O allele variant found in the Vindija Neanderthal is also found at very low frequency in East Asian individuals. Our genetic distance analyses suggests both alleles were introgressed through Neanderthal-human gene flow. In summary, our study identifies the genetic variation of the ABO gene in archaic humans, we find that ABO allele diversity in Neanderthals was likely high, and that some of these alleles still survive in modern humans due to inbreeding with Neanderthals.

The results are in alignment with theoretical expectations (which were probabilistic though). Alleles from these Eurasian hominins are probably beneficial in some way. Admixture with diverged lineages is a way to “rescue” diversity that may have been lost. The interesting point in the discussion though is that the Neanderthal population that the rare alleles were obtained had more variation than the small samples of European and Altai Neanderthals that we have now. This is not surprising, as it was probably a Near Eastern extension of European Neanderthals, and may even had have a larger long-term effective population than the groups further north.


The Wallacean Hominin Wonderland

A new preprint, Introgression, hominin dispersal and megafaunal survival in Late Pleistocene Island Southeast Asia, attempts to synthesize paleontology, biogeography, and human evolutionary genomics. It’s a pretty impressive effort, and short and compact:

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic super-archaic species, Homo luzonensis and H. floresiensis, were present around the time anatomically modern humans (AMH) arrived in the region >50,000 years ago. Contemporary human populations carry signals consistent with interbreeding events with Denisovans in ISEA, a species that is thought to be more closely related to AMH than the super-archaic endemic ISEA hominins. To query this disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes. Our results corroborate widespread Denisovan ancestry in ISEA populations but fail to detect any super-archaic admixture signals. By highlighting local megafaunal survival east of the Wallace Line as a potential signature of deep, pre-H. sapiens hominin-faunal interaction, we propose that this understudied region may hold the key to unlocking significant chapters in Denisovan prehistory.

Most paleonathropologists seem convinced now that Flores and the island of Luzon in the Phillipines were host to deeply diverged lineages of humans. By “deeply diverged” we’re talking well over one million years. Homo itself is only two million years ago. If they are deeply diverged there are ways to probe the genome for outlier segments of DNA which seem to have “come in” from outside lineages in relation to the main branch of ancestry. The more deeply diverged the ancestry, the easier it is to pick up the signal with even small amounts of admixture.

The authors could not find such ancestry in the various population across Southeast Asia and Australia, at least not to a greater extent than elsewhere. This implies that if luzonensis and floresiensis are deeply diverged they did not mix with anatomically modern humans. Or, the other option is that luzonensis and floresiensis are themselves Denisovans! In other words, luzonensis and floresiensis underwent strong adaptation to local conditions and changed so much that a standard morphological comparison will yield greater phylogenetic distance than what the whole genome might indicate. As we do not have ancient DNA from luzonensis and floresiensis this hypothesis cannot be tested.

But the model which the preprint seems to favor is that there are regions of island Southeast Asia with rich megafaunal survival, Sulawesi and Mindoro (an island off the coast of Luzon), that are also likely candidates for Denisovan remains. I would like the biogeographic element of the preprint fleshed out more before publication, though perhaps my relative confusion here is due to the fact that the evolutionary genomics is quite familiar to me.

I will note that the authors cite super-archaic admixture into the Andamanese, but from what I can tell most researchers in the area are skeptical of that particular paper. Basically, it looks like direct super-archaic admixture is unlikely. That being said, there are more complex models of indirect admixture through Neanderthals and Denisovans, and “first wave” modern humans, which I find possible.


How the Amazonians got their Australasian

Nature recently came out with two blockbuster papers establishing a better chronology on the settlement of the New World by humans. More precisely, the papers seem to push the likely date back by over 15,000 years. The figure above is from one of the papers. It shows human-derived artifacts from sites that date to 25,000 years BP and even 32,000 years BP.

I have recorded a podcast with the first author of one of the papers (she is second on the other). The podcast should post later today. Nevertheless, talking to the author I am more than 50% convinced that humans were present in the New World 32,000 years ago, and 90% convinced they were here 25,000 years ago. This is well before what is needed and expected from the standard “Beringian standstill” model.

The Beringian standstill alludes to the fact that the proto-Amerindians, a mix of Paleo-Siberian (ANE) and diverged East Asian, may have occupied Beringia for thousands of years before finally pushing southward ~15,000 years ago. The sites in the database of these papers show that a huge explosion of human occupation characterized North America during this period. But these were not the first humans.

I believe these new results likely open the possibility for a resolution of the mystery of why some groups in the Amazon seem to have “Australasian” genetic affinities. The result is robust. But it was hard to resolve with the Beringian standstill. The new chronology offers up an opportunity. Clearly the earlier populations before 20,000 years ago may have been the ancestors of the “Australasians” that are still hinted at in the Amazonians. I believe that these early people were members of what I have termed Clade-2 East Eurasians. This clade was dominant in South, Southeast Asia, Tibet, and present in coastal East Asia (Japan), during the Pleistocene. It has closer affinities to Oceanians than East Asians to the north.

If the first humans in the New World arrived as coastal fringe dwellers, it is clearly plausible that populations from Japan and points south could simply have done a circum-Pacific arc. We’ve seen lots of mass replacements in the ancient DNA, and the WST-Clovis groups seem to have been very numerous. Weak to no genetic signature of Clade-2 New World peoples is not surprising. There is no evidence of Oase Aurignacians in modern Europeans.


Let’s talk about sexual selection and Charles Darwin

Charles Darwin famously posited the origin of species through adaptation driven by natural selection. The theory of evolution as we understand it. But another of Darwin’s major ideas was that sexual selection was very important in driving diversity within species. More specifically Darwin thought that female choosiness was critical and explained why in species such as birds the males were so much more “showy.”

Sexual selection is a huge field of study, and it’s hard to deny that it is a real thing. But, there has long been an argument about the efficacy of sexual selection within humans. Depending on how you define it, it does not seem that humans are particularly sexually dimorphic compared to common chimpanzees and gorillas, for example. This goes back to whether we are polygynous or monogamous. Because of high reproductive variation for males in polygyny sexual selection can drive changes really fast (e.g., one super-fit male can produce huge numbers of offspring). The situation in monogamy is more difficult since there is less reproductive variance.

A new preprint seems to suggest that selection is happening on males, even today, due to deleterious genes. Sex-biased reduction in reproductive success drives selective constraint on human genes:

Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants. While genes under the strongest selective constraint are highly enriched for Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known. Here we show that genetic variants that damage these genes reduce reproductive success substantially in males but much less so in females. We present evidence that this reduction is mediated by cognitive and behavioural traits, which renders male carriers of such variants less likely to find mating partners. Our findings represent strong genetic evidence that Darwin’s theory of sexual selection is shaping the gene pool of contemporary human populations. Furthermore, our results suggest that sexual selection can account for about a quarter of all purifying selection acting on human genes.

The figure to the right gets at the major finding. More mutations mean a far more rapid drop in fitness for males than females. Why? The major reason seems to be that males can’t find a partner. If they can find a partner, the effect is much weaker. Basically, this is detecting an increase in childlessness.

A plausible explanation is that it impacts fertility, but the above indicates that that is not the case. And, the deleterious mutations aren’t enriched in the testes, nor does pruning out loci with known reproductive effects remove the impact. The authors also looked at intelligence. Those with mutations were not as intelligent, but that can’t explain most of the effect (and obviously it didn’t have much of an impact on women). The same with known conditions such as schizophrenia. Rather, what’s going on is that people are picking up on overall “genetic quality.”

There are major limitations of course. This is in British people. And, the samples from the Biobank tend to be somewhat healthier than average. There is a lot more work to be done with a lot more samples. But this is an awesome result in that it synthesizes the power and methods of modern genomics with a classical evolutionary hypothesis about the shape of human variation.

The main question I have regarding sexual selection then is what will the results in other societies be? As per Joe Henrich’s recent book, The WEIRDEST People in the World, the British have been in enforced monogamy for 1,000 years. Purifying selection could be much stronger in some non-WEIRD societies (and in inbred Arab cultures cousin-marriage would also ‘expose’ recessive alleles faster). That might mean there aren’t as many deleterious alleles. Or, it could be the effect is much stronger in those who have no children (males).

This is just the beginning. Perhaps it’s time to reread Geoffrey Miller’s The Mating Mind?


Humans like us in Sri Lanka 48,000 years ago

Bows and arrows and complex symbolic displays 48,000 years ago in the South Asian tropics:

Archaeologists contend that it was our aptitude for symbolic, technological, and social behaviors that was central to Homo sapiens rapidly expanding across the majority of Earth’s continents during the Late Pleistocene. This expansion included movement into extreme environments and appears to have resulted in the displacement of numerous archaic human populations across the Old World. Tropical rainforests are thought to have been particularly challenging and, until recently, impenetrable by early H. sapiens. Here, we describe evidence for bow-and-arrow hunting toolkits alongside a complex symbolic repertoire from 48,000 years before present at the Sri Lankan site of Fa-Hien Lena—the earliest bow-and-arrow technology outside of Africa. As one of the oldest H. sapiens rainforest sites outside of Africa, this exceptional assemblage provides the first detailed insights into how our species met the extreme adaptive challenges that were encountered in Asia during global expansion.

The most interesting aspect of this is that it is pretty close (a few thousand years earlier) to the date for the arrival of modern humans in Europe. The admixture with Neanderthals seems to be about 10,000 years earlier than this date, while that with Denisovans around this date. Something happened around 50,000 years ago, as a group of modern humans in and around the Near East seem to have radiated rapidly all across Eurasia, and later Oceania.

I assume that modern(ish) humans were present in Southeast Asia, but most of the ancestry dates to this period and pulse. A decade ago I might posit some incredible biological change, but cultural innovations in the Holocene triggered massive demographic shifts. There’s no reason the same couldn’t apply to the Pleistocene.


Biogeography, Denisovans, and Siberia

A new ancient DNA preprint, this time using the sequence of a 34,000-year-old sample from Northeastern Mongolia. The preprint is Denisovan ancestry and population history of early East Asians:

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in North East Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.

There are two major points in this preprint. First, as noted in the title, this adds weight to the inference that there were multiple admixtures between “Denisovan” populations and the peoples of south and east Eurasia. I put Denisovan in quotations because there is more and more evidence now that this was a diverse and variegated lineage of humans, not a simple classification such as Neanderthals, who often seem to have been closely related due to periodic population bottlenecks. This individual carries segments similar to the Altai Denisovan, and something different from the segments in the Papuans.

I think the second major aspect here is east-west gene flow in Eurasia in a bidirectional sense. It seems more and more likely that the “Ancient North Eurasians” (ANE) reflect two dynamics. First, the rapid expansion of an ancient West Eurasian branch of humans pushing up through the Near East and into Central Asia, and then Siberia, very early. Second, the assimilation and admixture with a minority element of incipient East Asian populations pushing up from the south. Though the trend was patchy and uneven, eventually the East Asian ancestral component kept increasing, until you have “Neo-Siberian” modern populations which are overwhelmingly East Asian.

Why the difference? As with Denisovans, I think the answer is a function of biogeography. Though West Eurasians had an easier “straight shot,” East Asians had a much larger reservoir population near at hand to the south over the late Pleistocene. Over time this resulted in a difference, whereby Siberian populations become more and more East Asians, with relatively little influx of West Eurasian genes until the Russian colonization.


Massive “Basal Eurasian” back-migration”

In 2005 Dienekes Pontikos had a post up, The mitochondrial time depth of humanity:

It is common to distinguish between Africans and non-Africans, with the former being much more genetically diverse than the latter. But, the real “gap” in human origins seems to be between the really old Africans (“Paleoafricans”) and the rest (“Afrasians”).

The Paleoafrican element is entirely confined to Africa, while the Afrasian one is found in both Africa and Eurasia. Indeed, modern humans can be entirely split into two groups: (i) a group of “pure” Afrasians which includes all non-Africans, and (ii) a group of Afrasian-Paleoafricans which includes all non-Caucasoid Africans. Human groups of entirely Paleoafrican origin, unhybridized with the younger Afrasians are no longer in existence.

Today, a preprint with very sophisticated computational methods of data analysis was posted, Ancient admixture into Africa from the ancestors of non-Africans. The figure to the right shows the proportion of deep “Eurasian” admixture into each major Sub-Saharan African population. Basically this preprint very formally breaks down the high likelihood that Dienekes’ model outlined in the mid-aughts was correct. Even back in 2008, there was an mtDNA phylogeny and coalescence that aligned well with his hypothesis: The Dawn of Human Matrilineal Diversity. Finally, there is the fact Y haplogroup E is dominant among non-hunter-gatherers in Africa, and it is within the “Eurasian-clade” DE.

The abstract of the new preprint makes the genome-wide results pretty clearly in alignment with the older uniparental evidence, as well as some interesting twists that one can infer from population genomics:

Genetic diversity across human populations has been shaped by demographic history, making it possible to infer past demographic events from extant genomes. However, demographic inference in the ancient past is difficult, particularly around the out-of-Africa event in the Late Middle Paleolithic, a period of profound importance to our species’ history. Here we present SMCSMC, a Bayesian method for inference of time-varying population sizes and directional migration rates under the coalescent-with-recombination model, to study ancient demographic events. We find evidence for substantial migration from the ancestors of present-day Eurasians into African groups between 40 and 70 thousand years ago, predating the divergence of Eastern and Western Eurasian lineages. This event accounts for previously unexplained genetic diversity in African populations, and supports the existence of novel population substructure in the Late Middle Paleolithic. Our results indicate that our species’ demographic history around the out-of-Africa event is more complex than previously appreciated.

The reason I put “Basal Eurasian” in the headline is that this is the “ghost population” postulated by the Reich group researchers in the first half of the teens to account for the fact that Mesolithic European hunter-gatherers seem to share more genetically with people such as Oceanians and Han Chinese in some ways that European “first farmers.” More precisely, the early West Asian farmer groups seem to be a mix of a population that is distinct as the “first branch” of non-African humanity, “Basal Eurasians”, and people related to West Eurasian Mesolithic hunter-gatherers. The latter place West Asians in the clade with Pleistocene Europeans and early Siberians, as a “western” group, while the former means that West Asians have ancestry that is more distant to Papuans and Amerindians than Mesolithic European hunter-gatherers.

Another thing that notable about Basal Eurasians is there is some circumstantial evidence that this population did not undergo much admixture with Neanderthals. This is important because the authors above report that the dominant signal of admixture between “40 and 70 thousand years ago” didn’t contribute Neanderthal admixture. Additionally, there’s the symmetrical distance from Han and European, which means that the gene-flow predates that divergence. Europeans have some Basal Eurasian admixture, so the symmetry might imply that this admixture is even basal to the Basal Eurasians (a Lazaridis et al. preprint suggests that there might be such a thing), though I’m not sure they have the statistical power to ascertain this. Rather, whatever this back-migration was, it probably doesn’t extend to a population beyond the Near East, and, it was probably just a bit before the massive “Out of Africa” break that happened ~55,000 years ago and is synchronous with Neanderthal admixture that we currently detect.

There are some things to reflect on in light of these data. First, crazy ideas sometimes are true. Reading Dienekes’ 2005 post today is not that exciting. It is quite plausible, perhaps right even. But in 2005 it seemed crazy. The “dogma” of a tree-like phylogeny and explosive “Out-of-Africa” event all over the world was pretty strong then. It was a robust prior and hard to entertain alternative models. But science advances, so here we are.

Second, terms like “Eurasian” and “African” do a little too much work. The ancestral lineages that we are thinking of here may not have been geographically where we assume using the geographical term. There is a good amount of evidence that the ancestors of the non-African lineage went through a protracted bottleneck. But we don’t know where this bottleneck occurred. We call it “non-African,” but perhaps the bottleneck occurred in Kenya? We don’t know. The bottleneck includes Basal Eurasians, so it predated Neanderthal admixture, and the massive radiation ~55-60,000 years ago. The most likely region is probably the Levant and Arabia. Sub-Saharan Africa seems to be lacking the geographic barriers such as a mega-desert or bodies to water to sustain barriers to gene-flow for thousands of years. But “most likely” does not mean overwhelmingly likely.

Preprints like the one above fill in a lot of general dynamics, but I think ancient DNA is going to be necessary to nail down the model tightly.

What can we expect? Honestly, we don’t know, but here is my general sense of what ancient DNA + better methods + more compute time (look at all the simulations!) + non-genetic information (paleontology, paleoclimate, paleo-everything) might tell us. Below is my best guess outline…

  • Proto-modern humans diversified in Africa 100 to 200 thousand years ago.
  • One branch related to eastern modern humans becomes isolated from other populations 75 to 100 thousand years ago
  • This branch is ancestral “non-Africans.” They are probably located in the southern Near East
  • But, in southeast Asia, there are other earlier expansions of modern human-related groups, which have mixed with local hominins
  • The expansion of the primary non-African group means that most of the signal of earlier Asian “moderns” is gone, though perhaps some of them are responsible for the Denisovan and other archaic signals
  • At the same time that the non-basal non-Africans are pushing east, the basal non-Africans are pushing west. The admixture between Basal Eurasians and African hunter-gatherers of various sorts results in the emergence of what we term Africans qua Africans. My working assumption is that the non-African ancestry in hunter-gatherer populations is due to continuous gene-flow from the primary synthetic groups
  • Archaic admixture everywhere there were earlier human groups

As Iain Mathieson once said, the story of the last few hundred thousand years is the collapse of old structure.


We are all Denisovans now!

Since 2010 the combination of improvements in genomic technology and ancient DNA have totally revolutionized our understanding of the human past through genetic techniques. In the 2000s there was a “live debate” about archaic introgression into modern human genomes, in large part because the techniques were not powerful enough to answer the questions that were being asked (nevertheless, many thought they really knew the answer already!).

With the sequencing of the Neanderthal in 2010 we saw that non-Africans seemed to carry more Neanderthal alleles than Africans, which was suggestive evidence of archaic admixture. Before the end of the year, the Denisovans were discovered, and it was clear that their impact was significant in the Papuans (and to some extent Oceanians generally). These discoveries were a shock already, but over the years more and more subtle discoveries have occurred. To some:

– Researchers believe that the Neanderthals have some ancestry from a basal modern population (a group that diverged a long time ago)

– Lots of debate about whether greater estimated Neanderthal fraction in East Asians was due to a second admixture or dilution of the original admixture by later mixing in West Eurasians, or, differential natural selection in different populations (I lean toward the middle position)

– It is clear that there is some Denisovan ancestry in East and South Asians, as well as in peoples of the New World. And, it seems quite clear that these admixtures were from different branches of the Denisovan group of humans

– It seems quite likely that Papuans may have multiple admixture events from Denisovan populations or from people related to the Denisovans

– There is lots of circumstantial evidence that Neanderthals and Denivosons may harbor ancestry from earlier human lineages that were present in Eurasia when their ancestors pushed out of Africa ~750,000 years ago

– Lots of evidence for deep ancestry admixture within Africa

– Basal Eurasians. What are they? We still don’t know!

Add to that list a new paper, The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes:

…humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50–60 thousand years ago1. Here we examine the effect of this event using 14.4 million putative archaic chromosome fragments that were detected in fully phased whole-genome sequences from 27,566 Icelanders, corresponding to a range of 56,388–112,709 unique archaic fragments that cover 38.0–48.2% of the callable genome. On the basis of the similarity with known archaic genomes, we assign 84.5% of fragments to an Altai or Vindija Neanderthal origin and 3.3% to Denisovan origin; 12.2% of fragments are of unknown origin. We find that Icelanders have more Denisovan-like fragments than expected through incomplete lineage sorting. This is best explained by Denisovan gene flow, either into ancestors of the introgressing Neanderthals or directly into humans…

The power of the Icelandic dataset is that they got really high coverage genomes, 30x, and phased them together to generate a lot of confident haplotypes. 3.3% Denisovan out of the 2-3% that’s archaic is really small. But if you have enough data you can find it.

They had to do simulations and run some HHMs to get here. I’m not sure I believe it. But I also think it’s plausible. The two models they present are:

– Denisovans mix into Neanderthals who mix into humans

– A Denisovan related population mixes into early non-African humans just before they mixed with Neanderthals

As time goes by I suspect we’ll find many small details of past interaction.