Selection and Reduced Population Size Cannot Explain Higher Amounts of Neandertal Ancestry in East Asian than in European Human Populations

It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data.     

Complex History of Admixture between Modern Humans and Neandertals

Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought.     

No evidence of Neandertal admixture in the mitochondrial genomes of early European modern humans and contemporary Europeans

Neandertals, the archaic human form documented in Eurasia until 29,000 years ago, share no mitochondrial haplotype with modern Europeans. Whether this means that the two groups were reproductively isolated is controversial, and indeed nuclear data have been interpreted as suggesting that they admixed. We explored the range of demographic parameters that may have generated the observed mitochondrial diversity, simulating 3.0 million genealogies under six models differing as for the relationships among contemporary Europeans, Neandertals, and Upper Palaeolithic European early modern humans (EEMH), who coexisted with Neandertals for millennia. We compared by Approximate Bayesian Computations the simulation results with mitochondrial diversity in 7 Neandertals, 3 EEMH, and 150 opportunely chosen modern Europeans. A model of genealogical continuity between EEMH and contemporary Europeans, with no Neandertal contribution, received overwhelming support from the analyses. The maximum degree of Neandertal admixture, under the model of gene flow supported by nuclear data, was estimated at 1.5%, but this model proved 20-32 times less likely than a model without any gene flow. Nuclear and mitochondrial evidence might be reconciled if smaller population sizes led to faster lineage sorting for mitochondrial DNA, and Neandertals shared a longer period of common ancestry with the non-African's than with the African's ancestors.     

An Extended Admixture Pulse Model Reveals the Limitations to Human–Neandertal Introgression Dating

Neandertal DNA makes up 2–3% of the genomes of all non-African individuals. The patterns of Neandertal ancestry in modern humans have been used to estimate that this is the result of gene flow that occurred during the expansion of modern humans into Eurasia, but the precise dates of this event remain largely unknown. Here, we introduce an extended admixture pulse model that allows joint estimation of the timing and duration of gene flow. This model leads to simple expressions for both the admixture segment distribution and the decay curve of ancestry linkage disequilibrium, and we show that these two statistics are closely related. In simulations, we find that estimates of the mean time of admixture are largely robust to details in gene flow models, but that the duration of the gene flow can only be recovered if gene flow is very recent and the exact recombination map is known. These results imply that gene flow from Neandertals into modern humans could have happened over hundreds of generations. Ancient genomes from the time around the admixture event are thus likely required to resolve the question when, where, and for how long humans and Neandertals interacted.     

Ancient DNA: would the real Neandertal please stand up?

Mitochondrial DNA sequences recovered from eight Neandertal specimens cannot be detected in either early fossil Europeans or in modern populations. This indicates that, if Neandertals made any genetic contribution at all to modern humans, it must have been limited, though the extent of the contribution cannot be resolved at present.     

Comparing models on the genealogical relationships among Neandertal, Cro-Magnoid and modern Europeans by serial coalescent simulations

Populations of anatomically archaic (Neandertal) and early modern (Cro-Magnoid) humans are jointly documented in the European fossil record, in the period between 40 000 and 25 000 years BP, but the large differences between their cultures, morphologies and DNAs suggest that the two groups were not close relatives. However, it is still unclear whether any genealogical continuity between them can be ruled out. Here, we simulated a broad range of demographic scenarios by means of a serial coalescence algorithm in which Neandertals, Cro-Magnoids and modern Europeans were either part of the same mitochondrial genealogy or of two separate genealogies. Mutation rates, population sizes, population structure and demographic growth rates varied across simulations. All models in which anatomically modern (that is, Cro-Magnoid and current) Europeans belong to a distinct genealogy performed better than any model in which the three groups were assigned to the same mitochondrial genealogy. The maximum admissible level of gene flow between Neandertals and the ancestors of current Europeans is 0.001% per generation, one order of magnitude lower than estimated in previous studies not considering genetic data on Cro-Magnoid people.     

Variation in modern human premolar enamel formation times: implications for Neandertals

A recent study demonstrated that variation in enamel cap crown formation in the anterior teeth is greater than that in the molars from two geographically distinct populations: native indigenous southern Africans and northern Europeans. Eighty southern African and 69 northern European premolars (P3 and P4) were analyzed in the present study. Cuspal, lateral, and total enamel formation times were assessed. Although cuspal enamel formation times were not consistently different between the two populations, both lateral and total enamel formation times generally were. Bonferroni-corrected t-tests showed that southern Africans had significantly shorter lateral enamel formation time for five of the six cusps, as well as significantly shorter total enamel formation time for these same cusps. An analysis of covariance performed on the lingual cusps of the upper third and fourth premolars showed that differences in enamel formation times between these populations remained when crown height was statistically controlled. A further goal of this study was to ascertain, based on perikymata counts, what Neandertal periodicities would have to be in order for their teeth to have lateral enamel formation times equivalent to either southern Africans or northern Europeans. To this end, perikymata were counted on 32 Neandertal premolars, and the counts were inserted into regression formulae relating perikymata counts to periodicity for each population and each tooth type. Neandertal enamel formation times could be equivalent to those of southern Africans or northern Europeans only if their hypothetical periodicities fall within the range of periodicities for African apes and modern humans (i.e., 6-12 days). The analysis revealed that both populations could encompass Neandertal timings, with hypothetical periodicities based on the southern African population necessitating a lower range of periodicity (6-8 days) than those based on the northern European population (8-11 days).     

The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.     

Zuttiyeh面骨

在以色列Zuttiyeh发现的额面骨破片距今至少已120,000年,认识到它如此古老就提示它有可能是任何地中海地区较晚居民的祖先。有些人认为它是早期尼安德特人,而另一些人则认为它是解剖学上已具现代特征的智人中的早期者。我们认为这个标本最适于与周口店直立人相对比。经过系统比较我们发现两者有着细节上的相似性。尽管两个地点在时间和空间距离上有差别。在本文中我们以人类进化地区连续性的解释讨论了这个相似性的含义。这对于理解晚更新世地中海地区居民的祖先及其关系是重要的。由于它表明亚洲至少是某些现生人类群体的重要发源地,所以对于现代人起源的“伊甸园”理论有着重要的含义。     

A reanalysis of the ancient mitochondrial DNA sequences recovered from Neandertal bones

Recent reports analyzing mitochondrial DNA sequences from Neandertal bones have claimed that Neandertals and modern humans are different species. The phylogenetic analyses carried out in these articles did not take into account the high substitution rate variation among sites observed in the human mitochondrial D-loop region and also lack an estimation of the parameters of the nucleotide substitution model. The separate phylogenetic position of Neandertals is not supported when these factors are considered. Our analysis shows that Neandertal-Human and Human-Human pairwise distance distributions overlap more than what previous studies suggested. We also show that the most ancient Neandertal HVI region is the most divergent when compared with modern human sequences. However, the opposite would be expected if the sequence had not been modified since the death of the specimen. Such incongruence is discussed in the light of diagenetic modifications in ancient Neandertal DNA sequences.     

The Date of Interbreeding between Neandertals and Modern Humans

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.     

A 28,000 years old Cro-Magnon mtDNA sequence differs from all potentially contaminating modern sequences

Background

DNA sequences from ancient speciments may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal) and early modern (Cro-Magnoid) Europeans.

Methodology/Principal Findings

We typed the mitochondrial DNA (mtDNA) hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23) and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences.

Conclusions/Significance:

The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans.     

Upper pleistocene human remains from Vindija cave,Croatia, Yugoslavia

Human remains excavated from Vindija cave include a large although fragmentary sample of late Mousterian-associated specimens and a few additional individuals from the overlying early Upper Paleolithic levels. The Mousterian-associated sample is similar to European Neandertals from other regions. Compared with earlier Neandertals from south central Europe, this sample evinces evolutionary trends in the direction of Upper Paleolithic Europeans. Compared with the western European Neandertals, the same trends can be demonstrated, although the magnitude of difference is less, and there is a potential for confusing temporal with regional sources of variation. The early Upper Paleolithic-associated sample cannot be distinguished from the Mousterian-associated hominids. We believe that this site provides support for Hrdli?ka's “Neandertal phase” of human evolution, as it was originally applied in Europe.     

Krapina 1: a juvenile Neandertal from the early late Pleistocene of Croatia

The juvenile A Skull from Krapina, Croatia (Krapina 1) has been the subject of considerable debate since B. Skerlj first suggested that it might not be a Neandertal. Although widely known by its original designation, the Krapina A Skull was recatalogued, along with all of the Krapina hominids, in the 1980's (Radovcic, et al., [1988]. The Krapina Hominids: An Illustrated Catalog of Skeletal Collection. Zagreb; Mladost). It is now catalogued as Krapina 1 in the archives of the Hrvatski Prirodoslovni Muzej, Zagreb, Croatia. We present a detailed, morphometric analysis of this specimen, comparing it to other Krapina specimens, juvenile late Pleistocene hominids (including Neandertals), and subadult recent humans. This analysis demonstrates that Krapina 1 possesses morphological features that are primitive retentions; others that represent derived Neandertal specializations; and still others that are typical for all European late Pleistocene humans. Morphological features associated with the browridges are intermediate between Neandertal and early modern European form. Nevertheless, a thorough analysis of the morphology of this specimen, in ontogenetic and regional contexts, leads to the conclusion that it cannot be excluded from the Neandertal range of variation. We conclude that the most parsimonious explanation for this 130 ka specimen is that it should be regarded as a Neandertal.     

An Australasian test of the recent African origin theory using the WLH-50 calvarium

This analysis investigates the ancestry of a single modern human specimen from Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its ancestry is important to our understanding of modern human origins in Australasia because the prevailing models of human origins make different predictions for the ancestry of this specimen, and others like it. Some authors believe in the validity of a complete replacement theory and propose that modern humans in Australasia descended solely from earlier modern human populations found in Late Pleistocene Africa and the Levant. These ancestral modern populations are believed to have completely replaced other archaic human populations, including the Ngandong hominids of Indonesia. According to this recent African origin theory, the archaic humans from Indonesia are classified as Homo erectus, a different evolutionary species that could not have contributed to the ancestry of modern Australasians. Therefore this theory of complete replacement makes clear predictions concerning the ancestry of the specimen WLH-50. We tested these predictions using two methods: a discriminant analysis of metric data for three samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference analysis of nonmetric data for individuals within these samples. The results of these procedures provide an unambiguous refutation of a model of complete replacement within this region, and indicate that the Ngandong hominids or a population like them may have contributed significantly to the ancestry of WLH-50. We therefore contend that Ngandong hominids should be classified within the evolutionary species, Homo sapiens. The Multiregional model of human evolution has the expectation that Australasian ancestry is in all three of the potentially ancestral groups and best explains modern Australasian origins.     

No evidence of Neandertal mtDNA contribution to early modern humans

The retrieval of mitochondrial DNA (mtDNA) sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution.     

Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers, and our results are thus also consistent with recent models that differentiate between the last common ancestor, expansion out of Africa, and the major expansion in human populations. Such a two-phase model is consistent with a wide range of molecular and archeological evidence.      

Relation of risk of systemic lupus erythematosus to west African admixture in a Caribbean population

Risk of systemic lupus erythematosus (SLE) is higher in people of west African descent than in Europeans. The objective of this study was to distinguish between genetic and environmental explanations for this ethnic difference by examining the relationship of disease risk to individual admixture (defined as the proportion of the genome that is of west African ancestry); 124 cases of SLE and 219 matched controls resident in Trinidad were studied. Analysis of admixture was restricted to 52 cases and 107 controls who reported no Indian or Chinese ancestry. These individuals were typed with a panel of 26 single-nucleotide polymorphisms and five insertion/deletion polymorphisms chosen to have large allele frequency differentials between west African, European and Native American populations. A Bayesian model for population admixture, individual admixture and locus ancestry was fitted by Markov chain simulation. Mean west African admixture (M) was 0.81 in cases and 0.74 in controls (P=0.01). The risk ratio for SLE associated with unit change in M was estimated as 32.5 with a 95% confidence interval (CI) of 2.0-518. Adjustment for measures of socioeconomic status (household amenities in childhood and years of education) altered this risk ratio only slightly (adjusted risk ratio: 28.4, 95% CI 1.7-485). These results support an additive genetic model for the ethnic difference in risk of SLE between west Africans and Europeans, rather than an environmental explanation or an "overdominant" model in which risk is higher in heterozygous than in homozygous individuals. This conclusion lays a basis for localizing the genes underlying this ethnic difference in risk of SLE by admixture mapping.     

Brief communication: paleoanthropology and the population genetics of ancient genes

The Mezmaiskaya cave mtDNA is similar in many ways to the Feldhofer cave Neandertal sequence and the more recently obtained Vindija cave sequence. If we accept the contention that the Mezmaiskaya cave specimen is a Neandertal infant, its mtDNA provides no new information about the fate of the European Neandertals. However, there is reason to believe that the Mezmaiskaya cave infant is not a Neandertal, and this places its importance in another light, because it delimits the possible hypotheses of Neandertal and recent human genetic relationships. One possibility is a that the pattern found in ancient mtDNA results from the replacement of an isolated gene pool (Neandertals) by one of its contemporaries (modern humans). A second possibility is natural selection expressed as the substitution of an advantageous mtDNA variant within a single large species, including both Neandertals and modern humans. The geologic, archaeological, and dating evidence shows the Mezmaiskaya cave infant to be a burial from a level even more recent than the Upper Paleolithic preserved at the site, and its anatomy does not contradict the assessment that the Mezmaiskaya cave infant is not a Neandertal. Therefore, the second pattern can be favored over the first.     

Testing multiregionality of modern human origins

In order to examine the possibility of multiple founding populations of anatomically modern Homo sapiens, we collected DNA sequence data from 10 X-chromosomal regions, 5 autosomal regions, and 1 Y-chromosomal region, in addition to mitochondrial DNA. Except for five regions which are genealogically uninformative and two other regions for which chimpanzee orthologs are not available, the ancestral sequence and population for each of the remaining regions were successfully inferred. Of these 10 ancestral sequences, 9 occurred in Africa and only 1 occurred in Asia during the Pleistocene. Computer simulation was carried out to quantify the multiregional hypothesis based solely on the premise that there was more than one founding population in the Pleistocene. Allowing the breeding size to vary among the founding populations, the hypothesis may account for the observed African ancestry in 90% of the genomic regions. However, it is required that the founding population in Africa was much larger than that outside Africa. Likelihood estimates of the breeding sizes in the founding populations were more than 9,000 in Africa and less than 1,000 in outside of Africa, although these estimates can be much less biased at the 1% significance level. If the number of African ancestral sequences further increases as more data accumulate in other genomic regions, the conclusion of a single founding population of modern H. sapiens is inevitable.