Another Introgressing Archaic Hominin Species?

Genetic Evidence of Archaic Introgression

Outside Africa

Somehow I missed a notable conclusion in a paper in Nature Genetics this summer on the genetic origins of the Andamanese people, and a related controversy over it.

This paper shows signs of a non-Neanderthal, non-Denisovan archaic hominin species 1-3% admixture (more if more recently diverged, less if less recently diverged) with a species diverged by about 400,000 years +100,000/-200,000 years from modern humans.[1] While this conclusion has certainly not reached a consensus level based upon this single paper, it is a very notable development. This would mean there were three separate archaic species that introgressed into modern humans outside Africa. The archaic species divergence estimated in the Andamanese study seems too recent to be a Homo Erectus, which should have diverged ca. 1,900,000 years ago when it left Africa, making Homo erectus too old a source for the archaic admixture that was reportedly observed. Another group of prominent researchers, however, was not able to replicate this result, published a refutation within a week, and thinks that it Andamanese paper is erroneous on this point.[2]

UPDATE March 21, 2017:

An April 30, 2014 pre-print at arXiv that I didn't mention thickens the plot (thanks to Ryan in the comment for pointing it out) reveals contributions from two more archaic hominin species to Eurasian genomes that diverged 859,000 and 3,464,000 years ago, both of which belong to common ancestors of modern humans and Neanderthals.[19] There is no indication, however, that the pre-print was ever published, so it may have gotten bogged down by hurdles or substantially revised over the course of the peer review process. The fact that only one of the many co-authors (Li Jin) has many publications in this area could also explain the lack of publication.

END UPDATE

In Africa

In addition there were probably probably one to four archaic species that introgressed into modern humans in Africa but not into modern humans outside Africa.[3][4][5][6] There is also the question of what to make of an extremely old African Y-DNA lineage, A00, which could just be an old modern human or proto-modern human lineage, or could be introgressed from an archaic hominin species.[7]

Matching Genetic Signs Of Introgression To Skeletal Remains

The alleged new introgressing species in South/Southeast Asia and in Africa are statistical ghosts derived from modern human genomes.

Denisovan admixture is associated with only by a few teeth and perhaps a knuckle in addition to a strong genetic signal in a few populations, although possibly a very weak signal in other Asian population.[8][9][10]

Only Neanderthals are represented by ample quantities of bones that have been tested for DNA.[11] Neanderthal introgression was found to have been very recent in an individual from 40,000 years ago in Romania whose ancient DNA was tested.[12] Introgression into Altai Neanderthals from modern humans suggests an introgression event ca. 100,000 years ago, predating the common ancestor of all modern humans outside Africa today and suggesting a two wave migration model for modern humans in which the first wave mostly failed.[13] Some African populations have some Neanderthal admixture due to Eurasian back migration.[14]

UPDATE March 23, 2017:

There were probably at least three distinct waves of Neanderthal admixture, in addition to one wave of Denisovan admixture.[20]

END UPDATE

And, while not precisely on point, modern human DNA from an individual who died 40,000 years ago in China has been extracted, which is distinctive East Eurasian rather than West Eurasian, and had modern levels of archaic hominin DNA, suggesting that little or no archaic admixture has taken place in East Asia since then.[15]

We also have bones from Homo floresiensis (a.k.a. hobbits) on the island of Flores, and bones from some archaic looking hominins in China not assigned to a species[16], but similar in brain capacity to modern humans and Neanderthals. We have no genetic information from either, but the former, due to its strategic location at the starting point of high levels of Denisovan DNA, and the latter, due to its evolutionary position and geographic location midway between the Altai and Flores, are both prime candidates for Denisovans.

We also have bones classified as Homo heidelbergensis (a.k.a. Homo rhodesiensis) that lived in Africa, Europe and western Asia between 600,000 and 200,000 years ago," which are both about right in terms of age to be an archaic species admixing with modern humans (somewhere, at least). And, we do have ancient DNA from H. heidelbergensis, which presents a complicated story. The mtDNA looked Denisovan,[17] but the nuclear DNA looked significantly more Neanderthal than Denisovan.[18] This "suggests the Neanderthal-Denisovan split happened before 430,000 years ago" (the date of the specimens from which the samples in Spain were taken). This fits with the notion that H. heidelbergensis is a parent clade to the Neanderthals and that Neanderthals and Denisovans are fairly closely related to each other (compared to modern humans and either Neanderthals or Denisovans). Homo heidelbergensis, or an immediate predecessor in Africa (or perhaps a slightly more remote predecessor like Homo ergaster), could also have been an ancestor (at least partially) of modern humans.

References

[1] Mayukh Mondal, et al., "Genomic analysis of Andamanese provides insights into ancient human migration into Asia and adaptation" 48 Nature Genetics 1066–1070 (July 25, 2016) (closed access; the open access supplemental materials are here). The abstract is as follows:

To shed light on the peopling of South Asia and the origins of the morphological adaptations found there, we analyzed whole-genome sequences from 10 Andamanese individuals and compared them with sequences for 60 individuals from mainland Indian populations with different ethnic histories and with publicly available data from other populations. 

We show that all Asian and Pacific populations share a single origin and expansion out of Africa, contradicting an earlier proposal of two independent waves of migration. We also show that populations from South and Southeast Asia harbor a small proportion of ancestry from an unknown extinct hominin, and this ancestry is absent from Europeans and East Asians. The footprints of adaptive selection in the genomes of the Andamanese show that the characteristic distinctive phenotypes of this population (including very short stature) do not reflect an ancient African origin but instead result from strong natural selection on genes related to human body size.

[2] Pontus Skoglund, Swapan Mallick, Nick Patterson, and David Reich, "No evidence for unknown archaic ancestry in South Asia", bioRxiv (August 1, 2016). The abstract is as follows:

Genomic studies have documented a contribution of archaic Neanderthals and Denisovans to non-Africans. Recently, Mondal et al. 2016 (Nature Genetics, doi:10.1038/ng.3621) published a major dataset--the largest whole genome sequencing study of diverse South Asians to date--including 60 mainland groups and 10 indigenous Andamanese. They reported analyses claiming that nearly all South Asians harbor ancestry from an unknown archaic human population that is neither Neanderthal nor Denisovan. However, the statistics cited in support of this conclusion do not replicate in other data sets, and in fact contradict the conclusion.

[3] Michael F. Hammer, et al., "Genetic evidence for archaic admixture in Africa" PNAS (2011). The abstract is as follows:

A long-debated question concerns the fate of archaic forms of the genus Homo: did they go extinct without interbreeding with anatomically modern humans, or are their genes present in contemporary populations? 

This question is typically focused on the genetic contribution of archaic forms outside of Africa. 

Here we use DNA sequence data gathered from 61 noncoding autosomal regions in a sample of three sub-Saharan African populations (Mandenka, Biaka, and San) to test models of African archaic admixture. We use two complementary approximate-likelihood approaches and a model of human evolution that involves recent population structure, with and without gene flow from an archaic population. 

Extensive simulation results reject the null model of no admixture and allow us to infer that contemporary African populations contain a small proportion of genetic material (≈2%) that introgressed ≈35 kya from an archaic population that split from the ancestors of anatomically modern humans ≈700 kya. Three candidate regions showing deep haplotype divergence, unusual patterns of linkage disequilibrium, and small basal clade size are identified and the distributions of introgressive haplotypes surveyed in a sample of populations from across sub-Saharan Africa. One candidate locus with an unusual segment of DNA that extends for >31 kb on chromosome 4 seems to have introgressed into modern Africans from a now-extinct taxon that may have lived in central Africa. Taken together our results suggest that polymorphisms present in extant populations introgressed via relatively recent interbreeding with hominin forms that diverged from the ancestors of modern humans in the Lower-Middle Pleistocene.

[4] J. Lachance, et al., "Evolutionary History and Adaptation from High-Coverage Whole-Genome Sequences of Diverse African Hunter-Gatherers" 150 Cell 457-469 (2012). The abstract is as follows:

To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at >603 coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation. 

We found evidence of archaic introgression in all three populations, and the distribution of time to most recent common ancestors from these regions is similar to that observed for introgressed regions in Europeans. 

Additionally, we identify numerous loci that harbor signatures of local adaptation, including genes involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing. Within the Pygmy population, we identify multiple highly differentiated loci that play a role in growth and anterior pituitary function and are associated with height.

The relevant section of the body text states (in part):

Hunter-Gatherer Genomes Possess Signatures of Archaic Admixture 

Gene flow between anatomically modern humans and archaic species has been described for European, Melanesian, and African populations (Hammer et al., 2011; Plagnol and Wall, 2006; Wall et al., 2009; Reich et al., 2010). 

To detect putatively introgressed regions in the Pygmy, Hadza, and Sandawe hunter-gatherer populations, we modified the summary statistic S*, which searches for clusters of population-specific SNPs in near complete LD, to be suitable for genome-scale analyses. S* has previously been used to detect archaic admixture in individuals of European and African descent (Hammer et al., 2011; Plagnol and Wall, 2006; Wall et al., 2009). We first verified that our implementation of S* could accurately identify introgressed regions by performing extensive coalescent simulations (Supplemental Information and Figure S7) and analyzing publicly available whole-genome sequences from nine CEPH and four Tuscan individuals sequenced by Complete Genomics. We calculated S* in 50 kb sliding windows and identified the top 350 regions (top 0.4%) in each population with unusually large values of S* as high-confidence candidates for introgression. TMRCA distributions for these regions are significantly larger than the distribution for all loci (p < 1016), consistent with the hypothesis that they are enriched for introgression (Figure 2A). Moreover, non-African genomic regions with high values of S* were significantly enriched for Neanderthal-specific SNPs (p < 1016, Figure 3B). Thus, S* can robustly detect genomic regions inherited from archaic ancestors. We next used S* to identify putatively introgressed regions in the African hunter-gatherer samples. 

In all three African hunter-gatherer samples, we found evidence of introgression from at least one archaic population. Strikingly, the median TMRCA for putatively introgressed haplotypes in the hunter-gatherer samples is similar to the median TMRCA for introgressed haplotypes in Europeans (1.2–1.3 Mya versus 1.1–1.2 Mya, respectively; Figure 2A), suggesting that the archaic African population diverged from anatomically modern humans in the same time frame as Neanderthals (simulations suggest that relative time of split with archaic populations can be recovered via TMRCA; Figure 3C). 

Additionally, we performed a STRUCTURE analysis of the putatively introgressed regions and of 350 random regions. If candidate regions identified by unusually large values of S* are enriched for genuine introgressed sequence, then we would expect STRUCTURE to identify two populations, as introgressed regions primarily consist of individuals carrying one archaic and one anatomically modern haplotype. In contrast, we would expect STRUCTURE to identify three populations in the randomly selected regions corresponding to the Pygmy, Hadza, and Sandawe populations. Indeed, this is precisely what we find (Figures 2B and 2C), further demonstrating that top-ranked S* regions are enriched for putatively introgressed sequence. 

There is significant overlap (p < 10^-16) among putatively introgressed regions in the three hunter-gatherer populations, consistent with either gene flow among the hunter-gatherer populations or introgression events that predate population splitting of these populations. In addition, the TMRCA of introgressed regions shared between all three populations is significantly older compared to introgressed regions observed in only one population (Wilcoxon rank-sum test, p = 2.2 x 10^-5; Figure 2D), consistent with an introgression event predating the divergence of these populations. In contrast, we observed few introgressed regions that overlap with those observed outside of Africa. One exception is a 2 Mb window on chromosome 8 (Figure 2E; chr8:3–5 Mb) that contains introgressed regions in all global populations. However, we note that because the chr8:3–5 Mb region is enriched for CNVs, it may be more prone to false positives (Supplemental Information). Id. . . .

Evidence of Archaic Introgression 

A striking finding in our data set is that compelling evidence exists that extant hunter-gatherer genomes contain introgressed archaic sequence, consistent with previous studies (Hammer et al., 2011; Plagnol and Wall, 2006; Reich et al., 2010; Shimada et al., 2007; Wall et al., 2009). 

We note that unambiguous evidence of introgression is difficult to obtain in the absence of an archaic reference sequence, which currently does not exist and may never be feasible given the rapid decay of fossils in Africa. Although we carefully filtered our data set in an attempt to analyze only high-quality sequences (Supplementary Information), it is possible that unrecognized structural variants or other alignment errors could generate a spurious signature similar to introgression. Encouragingly, we did not see an enrichment of structural variation calls in our candidate introgression regions. 

Additionally, through extensive simulations and analysis of European whole-genome sequences (Supplementary Information), we have demonstrated that the signatures of introgression that we observed are unlikely to be entirely accounted for due to other aspects of population demographic history, natural selection, or sequencing errors. Moreover, we did not find strong evidence that introgressed regions were clustered in the genome more often than expected by chance (p > 0.05; Supplemental Information). Nor did we find significant evidence that introgressed regions were enriched in genic regions (p > 0.05); rather, genic regions were significantly depleted for introgression in several populations (Supplemental Information). Therefore, the simplest interpretation of these data is that introgressed regions in extant human populations represent neutrally evolving vestiges of archaic sequences. In short, we find that low levels of introgression from an unknown archaic population or populations occurred in the three African hunter-gatherer samples examined, consistent with findings of archaic admixture in non-Africans (Reich et al., 2010).

[5] David Reich, et al., "Genetic history of anarchaic hominin group from Denisova Cave in Siberia." Nature 468, 1053–1060 (2010). The abstract is as follows:

Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4–6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population ‘Denisovans’ and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.

[6] R. Bohlender, et al., A complex history of archaic admixture in modern humans. (2016) (from the
ASHG 2016 (American Society for Human Genetics) Conference abstracts).

The sequencing of complete Neanderthal and Denisovan genomes has provided several insights into human history. One important insight stems from the observation that modern non-Africans and archaic populations share more derived alleles than they should if there was no admixture between them. We now know that the ancestors of modern non-Africans met, and introgressed with, Neanderthals and Denisovans.

The estimate of the quantity of shared derived alleles, the mixture proportion, rests on an assumption of no archaic admixture in African populations, and so African populations have been used as the “non-admixed” outgroup in prior analyses. We find that the story is likely more complex, that the history within Africa involves admixture with population(s) related to Neanderthal and Denisova, and that the mixture proportion estimates for non-African populations have been biased, particularly in Melanesia.

Here, we present results from a composite likelihood estimator of archaic admixture, which allows multiple sources of archaic admixture. We apply the method to archaic introgression, but it can be used to estimate ancient admixture among any four populations where the modeled assumptions are met. This joint estimate of Neanderthal and Denisovan admixture avoids the biases of previous estimators in populations with admixture from both Neanderthal and Denisova. To correct for dependence in our data, we use a moving blocks bootstrap to calculate confidence intervals.

With assumptions about population size and more recent population separation dates taken from the literature, we estimate the archaic-modern separation date at ~440,000 ± 300 years ago for all modern human populations. We also estimate the archaic-modern mixture proportion in the 1000 genomes, and the modern genomes sequenced with the high coverage Neanderthal and Denisovan genomes. 

We report those estimates here, support several prior findings, and provide evidence for a lower level of Denisovan admixture (0.0191 [0.0184, 0.0197]), relative to Neanderthal (0.0256 [0.0247, 0.0265]), in Melanesia. On the basis of an excess of shared derived alleles between San, Neanderthal, and Denisova we suggest that a third archaic population related more closely to Neanderthal and Denisova than to modern humans introgressed into the San genomes studied here.

[7] Fernando L. Mendez, et al., "An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree." 92 AJHG 454-459 (March 7, 2013). The abstract is as follows:

We report the discovery of an African American Y chromosome that carries the ancestral state of all SNPs that defined the basal portion of the Y chromosome phylogenetic tree. We sequenced ∼240 kb of this chromosome to identify private, derived mutations on this lineage, which we named A00. We then estimated the time to the most recent common ancestor (TMRCA) for the Y tree as 338 thousand years ago (kya) (95% confidence interval = 237–581 kya). 

Remarkably, this exceeds current estimates of the mtDNA TMRCA, as well as those of the age of the oldest anatomically modern human fossils. The extremely ancient age combined with the rarity of the A00 lineage, which we also find at very low frequency in central Africa, point to the importance of considering more complex models for the origin of Y chromosome diversity. These models include ancient population structure and the possibility of archaic introgression of Y chromosomes into anatomically modern humans. 

The A00 lineage was discovered in a large database of consumer samples of African Americans and has not been identified in traditional hunter-gatherer populations from sub-Saharan Africa. This underscores how the stochastic nature of the genealogical process can affect inference from a single locus and warrants caution during the interpretation of the geographic location of divergent branches of the Y chromosome phylogenetic tree for the elucidation of human origins.

[8] David Reich, et al., "Denisova Admixture and the First Modern Human Dispersals into Southeast Asia and Oceania" 89(4) AJHG 516-528 (October 7, 2011). The abstract is as follows:

It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. 

Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a “Negrito” group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. 

These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.

[9] Ping Hsun Hsieh, et al., "Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies" 26 Genome Research 291-300 (February 17, 2016). The abstract is as follows:

Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. 

Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. 

Here, we use statistical inference based on high coverage whole-genome data (greater than 60×) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing model-based whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr.

[10] P. Skoglund and M. Jakobsson, "Archaic Human Ancestry in East Asia", 108 PNAS 18301-18306 (2011). The abstract is as follows:

Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome--a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.

[11] Sriram Sankararaman, et al., "The Date of Interbreeding between Neandertals and Modern Humans" PLOS (October 4, 2012). The abstract is as follows:

Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. 

We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000–65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.

[12] Q. Fu, et al., "An early modern human from Romania with a recent Neanderthal ancestor" 524 Nature 216-219 (2015). The abstract is as follows:

Neanderthals are thought to have disappeared in Europe approximately 39,000-41,000 years ago but they have contributed 1-3% of the DNA of present-day people in Eurasia. Here we analyse DNA from a 37,000-42,000-year-old modern human from Pestera cu Oase, Romania. Although the specimen contains small amounts of human DNA, we use an enrichment strategy to isolate sites that are informative about its relationship to Neanderthals and present-day humans. We find that on the order of 6-9% of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe.

[13] Martin Kuhlwilm, et al., "Ancient gene flow from early modern humans into Eastern Neanderthals" 530 Nature 429–433 (February 25, 2016). The abstract is as follows:

It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

[14] Shuoguo Wang, et al., "Apparent Variation in Neanderthal Admixture among African Populations is Consistent with Gene Flow from Non-African Populations" 5(11) Genome Biol Evol 2075-2081 (October 25, 2013). The abstract is as follows:

Recent studies have found evidence of introgression from Neanderthals into modern humans outside of sub-Saharan Africa. Given the geographic range of Neanderthals, the findings have been interpreted as evidence of gene exchange between Neanderthals and modern humans descended from the Out-of-Africa (OOA) migration. 

Here, we examine an alternative interpretation in which the introgression occurred earlier within Africa, between ancestors or relatives of Neanderthals and a subset of African modern humans who were the ancestors of those involved in the OOA migration. Under the alternative model, if the population structure among present-day Africans predates the OOA migration, we might find some African populations show a signal of Neanderthal introgression whereas others do not. To test this alternative model, we compiled a whole-genome data set including 38 sub-Saharan Africans from eight populations and 25 non-African individuals from five populations. 

We assessed differences in the amount of Neanderthal-like single-nucleotide polymorphism alleles among these populations and observed up to 1.5% difference in the number of Neanderthal-like alleles among African populations. Further analyses suggest that these differences are likely due to recent non-African admixture in these populations. After accounting for recent non-African admixture, our results do not support the alternative model of older (e.g., >100 kya) admixture between modern humans and Neanderthal-like hominids within Africa.

[15] Qiaomei Fu, "DNA analysis of an early modern human from Tianjuan Cave, China." 110(6) PNAS 2223-2227 (February 5, 2013). The abstract is as follows:

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.

[16] Zhan-Yang Li, et al., "Late Pleistocene archaic human crainia from Xuchang, China" 355 Science 969-972 (March 3, 2017). Previously covered at this blog in this post. The significance statement and abstract are as follows:

Morphological mosaics in early Asian humans 

Excavations in eastern Asia are yielding information on human evolution and migration. Li et al. analyzed two fossil human skulls from central China, dated to 100,000 to 130,000 years ago. The crania elucidate the pattern of human morphological evolution in eastern Eurasia. Some features are ancestral and similar to those of earlier eastern Eurasian humans, some are derived and shared with contemporaneous or later humans elsewhere, and some are closer to those of Neandertals. The analysis illuminates shared long-term trends in human adaptive biology and suggests the existence of interconnections between populations across Eurasia during the later Pleistocene.

Abstract 

Two early Late Pleistocene (~105,000- to 125,000-year-old) crania from Lingjing, Xuchang, China, exhibit a morphological mosaic with differences from and similarities to their western contemporaries. They share pan–Old World trends in encephalization and in supraorbital, neurocranial vault, and nuchal gracilization. They reflect eastern Eurasian ancestry in having low, sagittally flat, and inferiorly broad neurocrania. They share occipital (suprainiac and nuchal torus) and temporal labyrinthine (semicircular canal) morphology with the Neandertals. This morphological combination reflects Pleistocene human evolutionary patterns in general biology, as well as both regional continuity and interregional population dynamics.

[17] Mattias Meyer, et al., "A mitochondrial genome sequence of a hominin from Sima de los Huesos" 505 Nature 403-406 (December 4, 2013). The abstract is as follows:

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 Holocene. One of these sites, the ‘Sima de los Huesos’ (‘pit of bones’), has yielded the world’s largest assemblage of Middle Pleistocene hominin fossils, consisting of at least 28 individuals dated to over 300,000 years ago. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits. 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, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.

[18] Mattias Meyer, et al., "Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins" 531 Nature 504-507 (March 14, 2016). The abstract is as follows:

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 ago. 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 Neanderthals. 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. 

UPDATE March 21, 2017:

[19] Ya Hu, et al., "Genome-wide Scan of Archaic Hominin Introgressions in Eurasians Reveals Complex Admixture" arXiv pre-print (April 30, 2014). The abstract to the paper is as follows:

Introgressions from Neanderthals and Denisovans were detected in modern humans. Introgressions from other archaic hominins were also implicated, however, identification of which poses a great technical challenge. 

Here, we introduced an approach in identifying introgressions from all possible archaic hominins in Eurasian genomes, without referring to archaic hominin sequences. We focused on mutations emerged in archaic hominins after their divergence from modern humans (denoted as archaic-specific mutations), and identified introgressive segments which showed significant enrichment of archaic-specific mutations over the rest of the genome. Furthermore, boundaries of introgressions were identified using a dynamic programming approach to partition whole genome into segments which contained different levels of archaic-specific mutations. 

We found that detected introgressions shared more archaic-specific mutations with Altai Neanderthal than they shared with Denisovan, and 60.3% of archaic hominin introgressions were from Neanderthals. Furthermore, we detected more introgressions from two unknown archaic hominins whom diverged with modern humans approximately 859 and 3,464 thousand years ago. The latter unknown archaic hominin contributed to the genomes of the common ancestors of modern humans and Neanderthals. In total, archaic hominin introgressions comprised 2.4% of Eurasian genomes. Above results suggested a complex admixture history among hominins. The proposed approach could also facilitate admixture research across species.

UPDATE March 23, 2017:

[20] Vernot, B., et al., "Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals." 352(6282) Science. :235-9 (March 17, 2016). The abstract is as follows:

Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 previously unknown Island Melanesian genomes. In aggregate, we recovered 1.34 gigabases and 303 megabases of the Neandertal and Denisovan genome, respectively. We use these maps of archaic sequences to show that Neandertal admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequences, and identify signatures of adaptive introgression.