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ABSTRACT: Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2(nd) to 9(th) cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100-300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount of DNA shared IBD in most ethnolinguistically-defined populations, for example Native American groups, Finns and Ashkenazi Jews, differs from continentally-defined populations by several orders of magnitude. Via extensive pedigree-based simulations, we determined bounds for predicted degrees of relationship given the amount of genomic IBD sharing in both endogamous and 'unrelated' population samples. Using these bounds as a guide, we detected tens of thousands of 2(nd) to 9(th) degree cousin pairs within a heterogenous set of 5,000 Europeans. The ubiquity of distant relatives, detected via IBD segments, in both ethnolinguistic populations and in large 'unrelated' populations samples has important implications for genetic genealogy, forensics and genotype/phenotype mapping studies.
PLoS ONE 01/2012; 7(4):e34267. · 4.09 Impact Factor
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Proceedings of the National Academy of Sciences 07/2011; 108(28):E278-E278. · 9.68 Impact Factor
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ABSTRACT: The invention of agriculture is widely assumed to have driven recent human population growth. However, direct genetic evidence for population growth after independent agricultural origins has been elusive. We estimated population sizes through time from a set of globally distributed whole mitochondrial genomes, after separating lineages associated with agricultural populations from those associated with hunter-gatherers. The coalescent-based analysis revealed strong evidence for distinct demographic expansions in Europe, southeastern Asia, and sub-Saharan Africa within the past 10,000 y. Estimates of the timing of population growth based on genetic data correspond neatly to dates for the initial origins of agriculture derived from archaeological evidence. Comparisons of rates of population growth through time reveal that the invention of agriculture facilitated a fivefold increase in population growth relative to more ancient expansions of hunter-gatherers.
Proceedings of the National Academy of Sciences 03/2011; 108(15):6044-9. · 9.68 Impact Factor
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Brenna M Henn,
Christopher R Gignoux,
Matthew Jobin,
Julie M Granka,
J M Macpherson,
Jeffrey M Kidd,
Laura Rodríguez-Botigué,
Sohini Ramachandran,
Lawrence Hon,
Abra Brisbin,
Alice A Lin,
Peter A Underhill,
David Comas,
Kenneth K Kidd,
Paul J Norman,
Peter Parham,
Carlos D Bustamante, Joanna L Mountain,
Marcus W Feldman
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ABSTRACT: Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ≠Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by F(ST), in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.
Proceedings of the National Academy of Sciences 03/2011; 108(13):5154-62. · 9.68 Impact Factor
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ABSTRACT: Previous research has established a discrepancy of nearly an order of magnitude between pedigree-based and phylogeny-based (human vs. chimpanzee) estimates of the mitochondrial DNA (mtDNA) control region mutation rate. We characterize the time dependency of the human mitochondrial hypervariable region one mutation rate by generating 14 new phylogeny-based mutation rate estimates using within-human comparisons and archaeological dates. Rate estimates based on population events between 15,000 and 50,000 years ago are at least 2-fold lower than pedigree-based estimates. These within-human estimates are also higher than estimates generated from phylogeny-based human-chimpanzee comparisons. Our new estimates establish a rapid decay in evolutionary mutation rate between approximately 2,500 and 50,000 years ago and a slow decay from 50,000 to 6 Ma. We then extend this analysis to the mtDNA-coding region. Our within-human coding region mutation rate estimates display a similar, though less rapid, time-dependent decay. We explore the possibility that multiple hits explain the discrepancy between pedigree-based and phylogeny-based mutation rates. We conclude that whereas nucleotide substitution models incorporating multiple hits do provide a possible explanation for the discrepancy between pedigree-based and human-chimpanzee mutation rate estimates, they do not explain the rapid decline of within-human rate estimates. We propose that demographic processes such as serial bottlenecks prior to the Holocene could explain the difference between rates estimated before and after 15,000 years ago. Our findings suggest that human mtDNA estimates of dates of population and phylogenetic events should be adjusted in light of this time dependency of the mutation rate estimates.
Molecular Biology and Evolution 12/2008; 26(1):217-30. · 5.55 Impact Factor
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ABSTRACT: We introduce REJECTOR, software for parameter estimation and comparison of alternate models of population history from genetic data via a rejection algorithm. Through coalescent simulation, REJECTOR generates numerous gene genealogies, and hence simulated data, under a model of population history specified by the user. Summary statistics derived from such simulated data are compared with observed statistics, leading to acceptance or rejection of a given set of parameter values. We performed tests of the software using known parameter values in order to assess the inferential power provided by each summary statistic. The tests demonstrate the precision and accuracy of estimation made possible using this approach. AVAILABILITY: http://www.rejector.org
Bioinformatics 11/2008; 24(24):2936-7. · 5.47 Impact Factor
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ABSTRACT: Although geneticists have extensively debated the mode by which agriculture diffused from the Near East to Europe, they have not directly examined similar agropastoral diffusions in Africa. It is unclear, for example, whether early instances of sheep, cows, pottery, and other traits of the pastoralist package were transmitted to southern Africa by demic or cultural diffusion. Here, we report a newly discovered Y-chromosome-specific polymorphism that defines haplogroup E3b1f-M293. This polymorphism reveals the monophyletic relationship of the majority of haplotypes of a previously paraphyletic clade, E3b1-M35*, that is widespread in Africa and southern Europe. To elucidate the history of the E3b1f haplogroup, we analyzed this haplogroup in 13 populations from southern and eastern Africa. The geographic distribution of the E3b1f haplogroup, in association with the microsatellite diversity estimates for populations, is consistent with an expansion through Tanzania to southern-central Africa. The data suggest this dispersal was independent of the migration of Bantu-speaking peoples along a similar route. Instead, the phylogeography and microsatellite diversity of the E3b1f lineage correlate with the arrival of the pastoralist economy in southern Africa. Our Y-chromosomal evidence supports a demic diffusion model of pastoralism from eastern to southern Africa approximately 2,000 years ago.
Proceedings of the National Academy of Sciences 09/2008; 105(31):10693-8. · 9.68 Impact Factor
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Sarah A Tishkoff,
Mary Katherine Gonder,
Brenna M Henn,
Holly Mortensen,
Alec Knight,
Christopher Gignoux,
Neil Fernandopulle,
Godfrey Lema,
Thomas B Nyambo,
Uma Ramakrishnan,
Floyd A Reed, Joanna L Mountain
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ABSTRACT: Little is known about the history of click-speaking populations in Africa. Prior genetic studies revealed that the click-speaking Hadza of eastern Africa are as distantly related to click speakers of southern Africa as are most other African populations. The Sandawe, who currently live within 150 km of the Hadza, are the only other population in eastern Africa whose language has been classified as part of the Khoisan language family. Linguists disagree on whether there is any detectable relationship between the Hadza and Sandawe click languages. We characterized both mtDNA and Y chromosome variation of the Sandawe, Hadza, and neighboring Tanzanian populations. New genetic data show that the Sandawe and southern African click speakers share rare mtDNA and Y chromosome haplogroups; however, common ancestry of the 2 populations dates back >35,000 years. These data also indicate that common ancestry of the Hadza and Sandawe populations dates back >15,000 years. These findings suggest that at the time of the spread of agriculture and pastoralism, the click-speaking populations were already isolated from one another and are consistent with relatively deep linguistic divergence among the respective click languages.
Molecular Biology and Evolution 10/2007; 24(10):2180-95. · 5.55 Impact Factor
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ABSTRACT: The Etruscans, the only preclassical European population that has been genetically characterized so far, share only two haplotypes with their modern geographic counterparts, the Tuscans, who, nonetheless, appear to be their closest relatives. We modeled 10 demographic scenarios spanning the last 2,500 years and tested by serial coalescent simulation whether any are consistent with the patterns of genetic diversity observed within and between the Etruscan and the modern Tuscan populations. Models in which the Etruscans are the direct ancestors of modern Tuscans appear compatible with the observed data only when they also include a very high mutation rate and an ancient founder effect. A better fit was obtained when the ancient and the modern samples were extracted from two independently evolving populations, connected by little migration. Simulated and observed parameters were also similar for a scenario in which the ancient samples came from a subset, e.g., a social elite, genetically differentiated from the bulk of the Etruscan population. In principle, these results may be biased by factors such as gross and systematic errors in the ancient DNA sequences and failure to sample suitable modern individuals. If neither proves to be the case, this study strongly suggests that either the mitochondrial mutation rate is much higher than currently believed or the Etruscans left very few modern mitochondrial descendants.
Proceedings of the National Academy of Sciences 06/2006; 103(21):8012-7. · 9.68 Impact Factor
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The Journal of Law Medicine & Ethics 02/2006; 34(2):248-62. · 1.22 Impact Factor
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ABSTRACT: Population bottlenecks wield a powerful influence on the evolution of species and populations by reducing the repertoire of responses available for stochastic environmental events. Although modern contractions of wild populations due to human-related impacts have been documented globally, discerning historic bottlenecks for all but the most recent and severe events remains a serious challenge. Genetic samples dating to different points in time may provide a solution in some cases. We conducted serial coalescent simulations to assess the extent to which temporal genetic data are informative regarding population bottlenecks. These simulations demonstrated that the power to reject a constant population size hypothesis using both ancient and modern genetic data is almost always higher than that based solely on modern data. The difference in power between the modern and temporal DNA approaches depends significantly on effective population size and bottleneck intensity and less significantly on sample size. The temporal approach provides more power in cases of genetic recovery (via migration) from a bottleneck than in cases of demographic recovery (via population growth). Choice of genetic region is critical, as mutation rate heavily influences the extent to which temporal sampling yields novel information regarding the demographic history of populations.
Molecular Ecology 10/2005; 14(10):2915-22. · 5.52 Impact Factor
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ABSTRACT: Summaries of human genomic variation shed light on human evolution and provide a framework for biomedical research. Variation is often summarised in terms of one or a few statistics (eg F(ST) and gene diversity). Now that multilocus genotypes for hundreds of autosomal loci are available for thousands of individuals, new approaches are applicable. Recently, trees of individuals and other clustering approaches have demonstrated the power of an individual-focused analysis. We propose analysing the distributions of genetic distances between individuals. Each distribution, or common ancestry profile (CAP), is unique to an individual, and does not require a priori assignment of individuals to populations. Here, we consider a range of models of population history and, using coalescent simulation, reveal the potential insights gained from a set of CAPs. Information lies in the shapes of individual profiles--sometimes captured by variance of individual CAPs--and the variation across profiles. Analysis of short tandem repeat genotype data for over 1,000 individuals from 52 populations is consistent with dramatic differences in population histories across human groups.
Human genomics 04/2005; 2(1):4-19.
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ABSTRACT: Descriptions of human genetic variation given thirty years ago have held up well, considering the substantial accrual of DNA sequence data in the interim. Most importantly, estimates of between-group genetic variation have remained relatively low. Despite the low average level of between-group variation, clusters recently inferred from multilocus genetic data coincide closely with groups defined by self-identified race or continental ancestry. This correspondence implies that genetic factors might contribute to unexplained between-group phenotypic variation. Current understanding of the contribution of genes to variation in most complex traits is limited, however. Under these circumstances, assumptions about genetic contributions to group differences are unfounded. In the absence of detailed understanding, 'racial' and 'ethnic' categories will remain useful in biomedical research. Further, we suggest approaches and guidelines for assessing the contribution of genetic factors to between-group phenotypic differences, including studies of candidate genes and analyses of recently admixed populations.
Nature Genetics 12/2004; 36(11 Suppl):S48-53. · 35.53 Impact Factor
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ABSTRACT: Inference of intraspecific population divergence patterns typically requires genetic data for molecular markers with relatively high mutation rates. Microsatellites, or short tandem repeat (STR) polymorphisms, have proven informative in many such investigations. These markers are characterized, however, by high levels of homoplasy and varying mutational properties, often leading to inaccurate inference of population divergence. A SNPSTR is a genetic system that consists of an STR polymorphism closely linked (typically < 500 bp) to one or more single-nucleotide polymorphisms (SNPs). SNPSTR systems are characterized by lower levels of homoplasy than are STR loci. Divergence time estimates based on STR variation (on the derived SNP allele background) should, therefore, be more accurate and precise. We use coalescent-based simulations in the context of several models of demographic history to compare divergence time estimates based on SNPSTR haplotype frequencies and STR allele frequencies. We demonstrate that estimates of divergence time based on STR variation on the background of a derived SNP allele are more accurate (3% to 7% bias for SNPSTR versus 11% to 20% bias for STR) and more precise than STR-based estimates, conditional on a recent SNP mutation. These results hold even for models involving complex demographic scenarios with gene flow, population expansion, and population bottlenecks. Varying the timing of the mutation event generating the SNP revealed that estimates of divergence time are sensitive to SNP age, with more recent SNPs giving more accurate and precise estimates of divergence time. However, varying both mutational properties of STR loci and SNP age demonstrated that multiple independent SNPSTR systems provide less biased estimates of divergence time. Furthermore, the combination of estimates based separately on STR and SNPSTR variation provides insight into the age of the derived SNP alleles. In light of our simulations, we interpret estimates from data for human populations.
Molecular Biology and Evolution 10/2004; 21(10):1960-71. · 5.55 Impact Factor
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New England Journal of Medicine 04/2003; 348(12):1170-5. · 53.30 Impact Factor
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ABSTRACT: About 30 languages of southern Africa, spoken by Khwe and San, are characterized by a repertoire of click consonants and phonetic accompaniments. The Jumid R:'hoansi (!Kung) San carry multiple deeply coalescing gene lineages. The deep genetic diversity of the San parallels the diversity among the languages they speak. Intriguingly, the language of the Hadzabe of eastern Africa, although not closely related to any other language, shares click consonants and accompaniments with languages of Khwe and San.
We present original Y chromosome and mtDNA variation of Hadzabe and other ethnic groups of Tanzania and Y chromosome variation of San and peoples of the central African forests: Biaka, Mbuti, and Lisongo. In the context of comparable published data for other African populations, analyses of each of these independently inherited DNA segments indicate that click-speaking Hadzabe and Jumid R:'hoansi are separated by genetic distance as great or greater than that between any other pair of African populations. Phylogenetic tree topology indicates a basal separation of the ancient ancestors of these click-speaking peoples. That genetic divergence does not appear to be the result of recent gene flow from neighboring groups.
The deep genetic divergence among click-speaking peoples of Africa and mounting linguistic evidence suggest that click consonants date to early in the history of modern humans. At least two explanations remain viable. Clicks may have persisted for tens of thousands of years, independently in multiple populations, as a neutral trait. Alternatively, clicks may have been retained, because they confer an advantage during hunting in certain environments.
Current Biology 04/2003; 13(6):464-73. · 9.65 Impact Factor
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ABSTRACT: Each independently evolving segment of the genomes of a sexually reproducing organism has a separate history reflecting part of the evolutionary history of that organism. Uniparentally or clonally inherited DNA segments such as the mitochondrial and chloroplast genomes and the nonrecombining portion of the Y chromosome have provided, to date, most of the known data regarding compound haplotypic variation within and among populations. These comparatively small segments include numerous polymorphic sites and undergo little or no recombination. Recombining autosomes, however, comprise the major repository of genetic variation. Technical challenges and recombination have limited large-scale application of autosomal haplotypes. We have overcome this barrier through development of a general approach to the assessment of short autosomal DNA segments. Each such segment includes one or more single nucleotide polymorphisms (SNPs) and exactly one short tandem repeat (STR) locus. With dramatically different mutation rates, these two types of genetic markers provide complementary evolutionary information. We call the combination of a SNP and a STR polymorphism a SNPSTR, and have developed a simple, rapid method for empirically determining gametic phase for double and triple heterozygotes. Here, we illustrate the approach with two SNPSTR systems. Although even one system provides insight into population history, the power of the approach lies in combining results from multiple SNPSTR systems.
Genome Research 12/2002; 12(11):1766-72. · 13.61 Impact Factor
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ABSTRACT: The ethnic heritage of northernmost New Spain, including present-day northern New Mexico and southernmost Colorado, USA, is intensely debated. Local Spanish-American folkways and anecdotal narratives led to claims that the region was colonized primarily by secret- or crypto-Jews. Despite ethnographic criticisms, the notion of substantial crypto-Jewish ancestry among Spanish-Americans persists.
We tested the null hypothesis that Spanish-Americans of northern New Mexico carry essentially the same profile of paternally inherited DNA variation as the peoples of Iberia, and the relevant alternative hypothesis that the sampled Spanish-Americans possess inherited DNA variation that reflects Jewish ancestry significantly greater than that in present-day Iberia.
We report frequencies of 19 Y-chromosome unique event polymorphism (UEP) biallelic markers for 139 men from across northern New Mexico and southern Colorado, USA, who self-identify as 'Spanish-American'. We used three different statistical tests of differentiation to compare frequencies of major UEP-defined clades or haplogroups with published data for Iberians, Jews, and other Mediterranean populations. We also report frequencies of derived UEP markers within each major haplogroup, compared with published data for relevant populations.
All tests of differentiation showed that, for frequencies of the major UEP-defined clades, Spanish-Americans and Iberians are statistically indistinguishable. All other pairwise comparisons, including between Spanish-Americans and Jews, and Iberians and Jews, revealed highly significant differences in UEP frequencies.
Our results indicate that paternal genetic inheritance of Spanish-Americans is indistinguishable from that of Iberians and refute the popular and widely publicized scenario of significant crypto-Jewish ancestry of the Spanish-American population.
Annals of Human Biology 33(1):100-11. · 1.98 Impact Factor
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