The history of African gene flow into Southern Europeans, Levantines, and Jews

Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas.     

Regional differences in the distribution of the sub-Saharan, West Eurasian, and South Asian mtDNA lineages in Yemen

Despite its key location for population movements out of and back into Africa, Yemen has not yet been sampled on a regional level for an investigation of sub-Saharan, West Eurasian, and South Asian genetic contributions. In this study, we present mitochondrial DNA (mtDNA) data for regionally distinct Yemeni populations that reveal different distributions of mtDNA lineages. An extensive database of mtDNA sequences from North and East African, Middle Eastern and Indian populations was analyzed to provide a context for the regional Yemeni mtDNA datasets. The groups of western Yemen appear to be most closely related to Middle Eastern and North African populations, while the eastern Yemeni population from Hadramawt is most closely related to East Africa. Furthermore, haplotype matches with Africa are almost exclusively confined to West Eurasian R0a haplogroup in southwestern Yemen, although more sub-Saharan L-type matches appear in more northern Yemeni populations. In fact, Yemeni populations have the highest frequency of R0a haplotypes detected to date, thus Yemen or southern Arabia may be the site of the initial expansion of this haplogroup. Whereas two variants of the sub-Saharan haplogroup M1 were detected only in southwestern Yemen close to the Bab el-Mandeb Strait, different non-African M haplotypes were detected at low frequencies (approximately 2%) in western parts of the country and at a higher frequency (7.5%) in the Hadramawt. We conclude that the Yemeni gene pool is highly stratified both regionally and temporally and that it has received West Eurasian, Northeast African, and South Asian gene flow.     

Elevated male European and female African contributions to the genomes of African American individuals

The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Restriction fragment length polymorphisms of type I collagen locus 2 (COL1A2) in two communities of African ancestry and other mixed populations of northwestern Ecuador

Restriction fragment length polymorphisms are good anthropological markers for discriminating geographically distinct populations at both the allele and the haplotype level. Two communities of African ancestry and ladinos, mestizos, and mulattoes living in the Esmeraldas province in northwestern Ecuador were analyzed for three RFLPs (EcoRI, RsaI, and MspI) of the COL1A2 gene. Also, the same markers were studied in a population sample from Spain to compare the allele and haplotype frequencies of the Esmeraldas populations with those of their representative European parental population. Data for the native American and sub-Saharan African founder components were available from the literature. No significant levels of differentiation between the two African Ecuadoran communities emerged from either the frequency analysis of each single marker and all three RFLP markers together or from the AMOVA. The ladinos and mestizos also showed a rather similar distribution of allele and haplotype frequencies, confirming that the two ethnic terms do not correspond to genetically different populations. The comparison with the supposed founding European, sub-Saharan African, and native American populations indicated a large presence of African genes in the gene pool of both communities, with a higher proportion of the Amerindian component in Viche than in Rio Cayapas. The present findings confirm the previous genetic admixture estimates based on nuclear and mitochondrial DNA markers and the demographic data.     

Asymmetric male and female genetic histories among Native Americans from Eastern North America

Previous studies have investigated the human population history of eastern North America by examining mitochondrial DNA (mtDNA) variation among Native Americans, but these studies could only reconstruct maternal population history. To evaluate similarities and differences in the maternal and paternal population histories of this region, we obtained DNA samples from 605 individuals, representing 16 indigenous populations. After amplifying the amelogenin locus to identify males, we genotyped 8 binary polymorphisms and 10 microsatellites in the male-specific region of the Y chromosome. This analysis identified 6 haplogroups and 175 haplotypes. We found that sociocultural factors have played a more important role than language or geography in shaping the patterns of Y chromosome variation in eastern North America. Comparisons with previous mtDNA studies of the same samples demonstrate that male and female demographic histories differ substantially in this region. Postmarital residence patterns have strongly influenced genetic structure, with patrilocal and matrilocal populations showing different patterns of male and female gene flow. European contact also had a significant but sex-specific impact due to a high level of male-mediated European admixture. Finally, this study addresses long-standing questions about the history of Iroquoian populations by suggesting that the ancestral Iroquoian population lived in southeastern North America.     

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.     

Genomic ancestry of North Africans supports back-to-Africa migrations

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from "back-to-Africa" gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa.     

Population Genomics of Sub-Saharan Drosophila melanogaster: African Diversity and Non-African Admixture

Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa F_ST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations.     

Reconstructing the population history of Nicaragua by means of mtDNA,Y‐chromosome STRs,and autosomal STR markers

Before the arrival of the Spaniards in Nicaragua, diverse Native American groups inhabited the territory. In colonial times, Native Nicaraguan populations interacted with Europeans and slaves from Africa. To ascertain the extent of this genetic admixture and provide genetic evidence about the origin of the Nicaraguan ancestors, we analyzed the mitochondrial control region (HVSI and HVSII), 17 Y chromosome STRs, and 15 autosomal STRs in 165 Mestizo individuals from Nicaragua. To carry out interpopulation comparisons, HVSI sequences from 29 American populations were compiled from the literature. The results reveal a close relationship between Oto‐manguean, Uto‐Aztecan, Mayan groups from Mexico, and a Chibchan group to Nicaraguan lineages. The Native American contribution to present‐day Nicaraguan Mestizos accounts for most of the maternal lineages, whereas the majority of Nicaraguan Y chromosome haplogroups can be traced back to a West Eurasian origin. Pairwise Fst distances based on Y‐STRs between Nicaragua and European, African and Native American populations show that Nicaragua is much closer to Europeans than the other populations. Additionally, admixture proportions based on autosomal STRs indicate a predominantly Spanish contribution. Our study reveals that the Nicaraguan Mestizo population harbors a high proportion of European male and Native American female substrate. Finally, the amount of African ancestry is also interesting, probably because of the contribution of Spanish conquerors with NorthAfrican genetic traces or that of West African slaves. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

Polymorphic Alu insertions and genetic diversity among African populations

Thorough assessment of modern genetic diversity and interpopulation affinities within the African continent is essential for understanding the processes that have been at work during the course of worldwide human evolution. Regardless of whether autosomal, Y-chromosome, or mtDNA markers are used, allele- or haplotype-frequency data from African populations are necessary in setting the framework for the construction of global population phylogenies. In the present study we analyze genetic differentiation and population structure in a data set of nine African populations using 12 polymorphic Alu insertions (PAls). Furthermore, to place our findings within a global context, we also examined an equal number of non-African groups. Frequency data from 456 individuals presented for the first time in this work plus additional data obtained from the literature indicate an overall pattern of higher intrapopulation diversity in sub-Saharan populations than in northern Africa, a prominent differentiation between these two locations, an appreciably high degree of transcontinental admixture in Egypt, and significant discontinuity between Morocco and the Iberian peninsula. Moreover, the topologies of our phylogenetic analyses suggest that out of the studied sub-Saharan groups, the southern Bantu population of Sotho/ Tswana presents the highest level of antiquity, perhaps as a result of ancestral or acquired Khoisan genetic signals. Close affinities of eastern sub-Saharan populations with Egypt in the phylogenetic trees may indicate the existence of gene flow along the Nile River.     

The Kalash Genetic Isolate: Ancient Divergence,Drift, and Selection

The Kalash represent an enigmatic isolated population of Indo-European speakers who have been living for centuries in the Hindu Kush mountain ranges of present-day Pakistan. Previous Y chromosome and mitochondrial DNA markers provided no support for their claimed Greek descent following Alexander III of Macedon''s invasion of this region, and analysis of autosomal loci provided evidence of a strong genetic bottleneck. To understand their origins and demography further, we genotyped 23 unrelated Kalash samples on the Illumina HumanOmni2.5M-8 BeadChip and sequenced one male individual at high coverage on an Illumina HiSeq 2000. Comparison with published data from ancient hunter-gatherers and European farmers showed that the Kalash share genetic drift with the Paleolithic Siberian hunter-gatherers and might represent an extremely drifted ancient northern Eurasian population that also contributed to European and Near Eastern ancestry. Since the split from other South Asian populations, the Kalash have maintained a low long-term effective population size (2,319–2,603) and experienced no detectable gene flow from their geographic neighbors in Pakistan or from other extant Eurasian populations. The mean time of divergence between the Kalash and other populations currently residing in this region was estimated to be 11,800 (95% confidence interval = 10,600−12,600) years ago, and thus they represent present-day descendants of some of the earliest migrants into the Indian sub-continent from West Asia.     

Contrasting signatures of population growth for mitochondrial DNA and Y chromosomes among human populations in Africa

A history of Pleistocene population expansion has been inferred from the frequency spectrum of polymorphism in the mitochondrial DNA (mtDNA) of many human populations. Similar patterns are not typically observed for autosomal and X-linked loci. One explanation for this discrepancy is a recent population bottleneck, with different rates of recovery for haploid and autosomal loci as a result of their different effective population sizes. This hypothesis predicts that mitochondrial and Y chromosomal DNA will show a similar skew in the frequency spectrum in populations that have experienced a recent increase in effective population size. We test this hypothesis by resequencing 6.6 kb of noncoding Y chromosomal DNA and 780 basepairs of the mtDNA cytochrome c oxidase subunit III (COIII) gene in 172 males from 5 African populations. Four tests of population expansion are employed for each locus in each population: Fu's Fs statistic, the R(2) statistic, coalescent simulations, and the mismatch distribution. Consistent with previous results, patterns of mtDNA polymorphism better fit a model of constant population size for food-gathering populations and a model of population expansion for food-producing populations. In contrast, none of the tests reveal evidence of Y chromosome growth for either food-gatherers or food-producers. The distinct mtDNA and Y chromosome polymorphism patterns most likely reflect sex-biased demographic processes in the recent history of African populations. We hypothesize that males experienced smaller effective population sizes and/or lower rates of migration during the Bantu expansion, which occurred over the last 5,000 years.     

Land, language, and loci: mtDNA in Native Americans and the genetic history of Peru

Despite a long history of complex societies and despite extensive present-day linguistic and ethnic diversity, relatively few populations in Peru have been sampled for population genetic investigations. In order to address questions about the relationships between South American populations and about the extent of correlation between genetic distance, language, and geography in the region, mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup markers were examined in 33 individuals from the state of Ancash, Peru. These sequences were compared to those from 19 American Indian populations using diversity estimates, AMOVA tests, mismatch distributions, a multidimensional scaling plot, and regressions. The results show correlations between genetics, linguistics, and geographical affinities, with stronger correlations between genetics and language. Additionally, the results suggest a pattern of differential gene flow and drift in western vs. eastern South America, supporting previous mtDNA and Y chromosome investigations.     

Variation of female and male lineages in sub-Saharan populations: the importance of sociocultural factors

In this paper, we present a study of genetic variation in sub-Saharan Africa, which is based on published and unpublished data on fast-evolving (hypervariable region 1 of mitochondrial DNA and six microsatellites of Y chromosome) and slow-evolving (haplogroup frequencies) polymorphisms of mtDNA and Y chromosome. Our study reveals a striking difference in the genetic structure of food-producer (Bantu and Sudanic speakers) and hunter-gatherer populations (Pygmies, Kung, and Hadza). In fact, the ratio of mtDNA to Y-chromosome Nupsilon is substantially higher in food producers than in hunter-gatherers as determined by fast-evolving polymorphisms (1.76 versus 0.11). This finding indicates that the two population groups differ substantially in female and male migration rate and/or effective size. The difference also persists when linguistically homogeneous populations are used and outlier populations are eliminated (1.78 vs 0.19) or when the jacknife procedure is applied to a paired population data set (1.32 to 7.84 versus 0.14 to 0.66). The higher ratio of mtDNA to Y-chromosome Nnu in food producers than in hunter-gatherers is further confirmed by the use of slow-evolving polymorphisms (1.59 to 7.91 versus 0.12 to 0.35). To explain these results, we propose a model that integrates demographic and genetic aspects and incorporates ethnographic knowledge. In such a model, the asymmetric gene flow, polyginy, and patrilocality play an important role in differentiating the genetic structure of sub-Saharan populations. The existence of an asymmetric gene flow is supported by the phylogeographic features of mtDNA and Y-chromosome haplogroups found in the two population groups. The role of polyginy and patrilocality is sustained by the evidence of a differential pressure of genetic drift and gene flow on maternal and paternal lineages of food producers and hunter-gatherers that is revealed through the analysis of mitochondrial and Y-chromosomal intrapopulational variation.     

Heterogeneity of the Y chromosome in Afro-Brazilian populations

Sixteen biallelic markers (SRY10831a, SRY10831b, SRY4064, SRY2627, 92R7, P2, P3, M34, M9, M3, M2, YAP, M60, M89, M213, M216) located in the nonrecombinant region of the Y chromosome were analyzed in 209 individuals belonging to six Brazilian populations: four Afro-Brazilian populations, one population of white European descendants, and one population of Japanese descendants. The results showed that most of the Y chromosomes of the Afro-Brazilians were from sub-Saharan Africa and that the proportion of Y chromosomes of European origin was greater than that of Y chromosomes of Amerindian origin. No typical African or Amerindian haplogroup was detected among Japanese individuals, and only one white individual showed a typical African haplogroup. Haplogroup P-92R7, which is highly frequent in the Portuguese and Italian populations, was the most frequent among whites (54%), and haplogroup K-M9, which shows wide geographic distribution and is absent in Africa, was the most frequent among Japanese individuals (65.6%). The two semi-isolated Afro-Brazilian populations showed the highest and the lowest genetic diversity, respectively. These differences probably reflect the effect of greater or smaller gene flow between a small isolated group and other populations. These findings show that the process of admixture does not occur homogeneously, with a tendency toward preferential marriages within the ethnic group and a clear direction in unions between European men and Amerindian or African women in the past. The results agree with historical and social data about the formation of the Brazilian population and reveal some of the factors that contribute to its heterogeneity.     

Ancient DNA reveals a migration of the ancient Di‐qiang populations into Xinjiang as early as the early Bronze Age

Xinjiang is at the crossroads between East and West Eurasia, and it harbors a relatively complex genetic history. In order to better understand the population movements and interactions in this region, mitochondrial and Y chromosome analyses on 40 ancient human remains from the Tianshanbeilu site in eastern Xinjiang were performed. Twenty‐nine samples were successfully assigned to specific mtDNA haplogroups, including the west Eurasian maternal lineages of U and W and the east Eurasian maternal lineages of A, C, D, F, G, Z, M7, and M10. In the male samples, two Y chromosome haplogroups, C* and N1 (xN1a, N1c), were successfully assigned. Our mitochondrial and Y‐chromosomal DNA analyses combined with the archaeological studies revealed that the Di‐qiang populations from the Hexi Corridor had migrated to eastern Xinjiang and admixed with the Eurasian steppe populations in the early Bronze Age. Am J Phys Anthropol 157:71–80, 2015. © 2014 Wiley Periodicals, Inc.     

Extensive female-mediated gene flow from sub-Saharan Africa into near eastern Arab populations

We have analyzed and compared mitochondrial DNA variation of populations from the Near East and Africa and found a very high frequency of African lineages present in the Yemen Hadramawt: more than a third were of clear sub-Saharan origin. Other Arab populations carried approximately 10% lineages of sub-Saharan origin, whereas non-Arab Near Eastern populations, by contrast, carried few or no such lineages, suggesting that gene flow has been preferentially into Arab populations. Several lines of evidence suggest that most of this gene flow probably occurred within the past approximately 2,500 years. In contrast, there is little evidence for male-mediated gene flow from sub-Saharan Africa in Y-chromosome haplotypes in Arab populations, including the Hadramawt. Taken together, these results are consistent with substantial migration from eastern Africa into Arabia, at least in part as a result of the Arab slave trade, and mainly female assimilation into the Arabian population as a result of miscegenation and manumission.     

Deep divergences of human gene trees and models of human origins

Two competing hypotheses are at the forefront of the debate on modern human origins. In the first scenario, known as the recent Out-of-Africa hypothesis, modern humans arose in Africa about 100,000-200,000 years ago and spread throughout the world by replacing the local archaic human populations. By contrast, the second hypothesis posits substantial gene flow between archaic and emerging modern humans. In the last two decades, the young time estimates--between 100,000 and 200,000 years--of the most recent common ancestors for the mitochondrion and the Y chromosome provided evidence in favor of a recent African origin of modern humans. However, the presence of very old lineages for autosomal and X-linked genes has often been claimed to be incompatible with a simple, single origin of modern humans. Through the analysis of a public DNA sequence database, we find, similar to previous estimates, that the common ancestors of autosomal and X-linked genes are indeed very old, living, on average, respectively, 1,500,000 and 1,000,000 years ago. However, contrary to previous conclusions, we find that these deep gene genealogies are consistent with the Out-of-Africa scenario provided that the ancestral effective population size was approximately 14,000 individuals. We show that an ancient bottleneck in the Middle Pleistocene, possibly arising from an ancestral structured population, can reconcile the contradictory findings from the mitochondrion on the one hand, with the autosomes and the X chromosome on the other hand.     

Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins

Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations.     

Ancient DNA and the population genetics of cave bears (Ursus spelaeus) through space and time

The cave bear spread from Western Europe to the Near East during the Riss glaciation (250 KYA) before becoming extinct approximately 12 KYA. During that period, the climatic conditions were highly dynamic, oscillating between glacial and temperate episodes. Such events have constrained the geographic repartition of species, the movements of populations and shaped their genetic diversity. We retrieved and analyzed ancient DNA from 21 samples from five European caves ranging from 40 to 130 KYA. Combined with available data, our data set accounts for a total of 41 sequences of cave bear, coming from 18 European caves. We distinguish four haplogroups at the level of the mitochondrial DNA control region. The large population size of cave bear could account for the maintenance of such polymorphism. Extensive gene flow seems to have connected European populations because two haplogroups cover wide geographic areas. Furthermore, the extensive sampling of the deposits of the Scladina cave located in Belgium allowed us to correlate changes in climatic conditions with the intrapopulational genetic diversity over 90 KY.