Ancestral Source Populations Research Articles

Ancestral Origins and Admixture History of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin, genomic makeup, and genetic interaction with surrounding populations are not well understood. To decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from 4 ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from the Uyghurs in terms of their overall genomic makeup, although the 2 populations were closely related in genetics, and both showed a substantial admixture of western and eastern peoples. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those living or along the old Silk Road.

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

Patterns of Genetic And Epigenetic Diversity Across A Range Expansion in The White-Footed Mouse (Peromyscus Leucopus).

Populations at the leading front of a range expansion must rapidly adapt to novel conditions. Increased epigenetic diversity has been hypothesized to facilitate adaptation and population persistence via non-genetic phenotypic variation, especially if there is reduced genetic diversity when populations expand (i.e., epigenetic diversity compensates for low genetic diversity). In this study, we use the spatial distribution of genetic and epigenetic diversity to test this hypothesis in populations of the white-footed mouse (Peromyscus leucopus) sampled across a purported recent range expansion gradient. We found mixed support for the epigenetic compensation hypothesis and a lack of support for expectations for expansion populations of mice at the range edge, which likely reflects a complex history of expansion in white-footed mice in the Upper Peninsula of Michigan. Specifically, epigenetic diversity was not increased in the population at the purported edge of the range expansion in comparison to the other expansion populations. However, input from an additional ancestral source populations may have increased genetic diversity at this range edge population, counteracting the expected genetic consequences of expansion, as well as reducing the benefit of increased epigenetic diversity at the range edge. Future work will expand the focal populations to include expansion areas with a single founding lineage to test for the robustness of a general trend that supports the hypothesized compensation of reduced genetic diversity by epigenetic variation observed in the expansion population that was founded from a single historical source.

Testing the existence of an unadmixed ancestor from a specific population t generations ago.

The ancestry of each locus of the genome can be estimated (local ancestry) based on sequencing or genotyping information together with reference panels of ancestral source populations. The length of those ancestry-specific genomic segments are commonly used to understand migration waves and admixture events. In short time scales, it is often of interest to determine the existence of the most recent unadmixed ancestor from a specific population t generations ago. We built a hypothesis test to determine if an individual has an ancestor belonging to a target ancestral population t generations ago based on these lengths of the ancestry-specific segments at an individual level. We applied this test on a data set that includes 20 Uruguayan admixed individuals to estimate for each one how many generations ago the most recent indigenous ancestor lived. As this method tests each individual separately, it is particularly suited to small sample sizes, such as our study or ancient genome samples.

Disentangling Signatures of Selection Before and After European Colonization in Latin Americans.

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

Postglacial colonization in the Great Lakes Region by the white-footed mouse (Peromyscus leucopus): conflicts between genomic and field data

Abstract For regions that were covered by ice during the Pleistocene glaciations, species must have emigrated from unglaciated regions. However, it can be difficult to discern when and from what ancestral source populations such expansions took place, especially since warming climates introduce the possibility of very recent expansions. For example, in the Great Lakes region, pronounced climatic change includes past glaciations as well as recent, rapid warming. Here we evaluate different expansion hypotheses with a genomic study of the white-footed mouse (Peromyscus leucopus noveboracensis), which is one of the most common mammals throughout the Great Lakes region. Ecological surveys coupled with historical museum records suggest a recent range expansion of P. leucopus associated with the warming climate over the last decades. These detailed records have yet to be complemented by genomic data that provide the requisite resolution for detecting recent expansion, although some mitochondrial DNA (mtDNA) sequences have suggested possible hypotheses about the geography of expansion. With more than 7,000 loci generated using RADseq, we evaluate support for multiple hypotheses of a geographic expansion in the Upper Peninsula of Michigan (UP). Analysis of a single random single-nucleotide polymorphism per locus revealed a fine-scale population structure separating the Lower Peninsula (LP) population from all other populations in the UP. We also detected a genetic structure that reflects an evolutionary history of postglacial colonization from two different origins into the UP, one coming from the LP and one coming from the west. Instead of supporting a climate-driven range expansion, as suggested by field surveys, our results support more ancient postglacial colonization of the UP from two different ancestral sources. With these results, we offer new insights about P. leucopus geographic expansion history, as well as a more general phylogeographic framework for testing range shifts in the Great Lakes region.

Genomic diversity and post-admixture adaptation in the Uyghurs.

Population admixture results in genome-wide combinations of genetic variants derived from different ancestral populations of distinct ancestry, thus providing a unique opportunity for understanding the genetic determinants of phenotypic variation in humans. Here, we used whole-genome sequencing of 92 individuals with high coverage (30–60×) to systematically investigate genomic diversity in the Uyghurs living in Xinjiang, China (XJU), an admixed population of both European-like and East-Asian-like ancestry. The XJU population shows greater genetic diversity, especially a higher proportion of rare variants, compared with their ancestral source populations, corresponding to greater phenotypic diversity of XJU. Admixture-induced functional variants in EDAR were associated with the diversity of facial morphology in XJU. Interestingly, the interaction of functional variants between SLC24A5 and OCA2 likely influences the diversity of skin pigmentation. Notably, selection has seemingly been relaxed or canceled in several genes with significantly biased ancestry, such as HERC2–OCA2. Moreover, signatures of post-admixture adaptation in XJU were identified, including genes related to metabolism (e.g. CYP2D6), digestion (e.g. COL11A1), olfactory perception (e.g. ANO2) and immunity (e.g. HLA). Our results demonstrated population admixture as a driving force, locally or globally, in shaping human genetic and phenotypic diversity as well as in adaptive evolution.

Simulation-Based Evaluation of Three Methods for Local Ancestry Deconvolution of Non-model Crop Species Genomes.

Hybridizations between species and subspecies represented major steps in the history of many crop species. Such events generally lead to genomes with mosaic patterns of chromosomal segments of various origins that may be assessed by local ancestry inference methods. However, these methods have mainly been developed in the context of human population genetics with implicit assumptions that may not always fit plant models. The purpose of this study was to evaluate the suitability of three state-of-the-art inference methods (SABER, ELAI and WINPOP) for local ancestry inference under scenarios that can be encountered in plant species. For this, we developed an R package to simulate genotyping data under such scenarios. The tested inference methods performed similarly well as far as representatives of source populations were available. As expected, the higher the level of differentiation between ancestral source populations and the lower the number of generations since admixture, the more accurate were the results. Interestingly, the accuracy of the methods was only marginally affected by i) the number of ancestries (up to six tested); ii) the sample design (i.e., unbalanced representation of source populations); and iii) the reproduction mode (e.g., selfing, vegetative propagation). If a source population was not represented in the data set, no bias was observed in inference accuracy for regions originating from represented sources and regions from the missing source were assigned differently depending on the methods. Overall, the selected ancestry inference methods may be used for crop plant analysis if all ancestral sources are known.

Genetic ancestry, admixture and health determinants in Latin America

BackgroundModern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico.ResultsWe analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population’s genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects.ConclusionsAncestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.

The Columbian Exchange as a source of adaptive introgression in human populations.

BackgroundThe term “Columbian Exchange” refers to the massive transfer of life between the Afro-Eurasian and American hemispheres that was precipitated by Columbus’ voyage to the New World. The Columbian Exchange is widely appreciated by historians, social scientists and economists as a major turning point that had profound and lasting effects on the trajectory of human history and development.Presentation of the hypothesisI propose that the Columbian Exchange should also be appreciated by biologists for its role in the creation of novel human genomes that have been shaped by rapid adaptive evolution. Specifically, I hypothesize that the process of human genome evolution stimulated by the Columbian Exchange was based in part on selective sweeps of introgressed haplotypes from ancestral populations, many of which possessed pre-evolved adaptive utility based on regional-specific fitness and health effects.Testing the hypothesisTesting of this hypothesis will require comparative analysis of genome sequences from putative ancestral source populations, with genomes from modern admixed populations, in order to identify ancestry-specific introgressed haplotypes that exist at higher frequencies in admixed populations than can be expected by chance alone. Investigation of such ancestry-enriched genomic regions can be used to provide clues as to the functional roles of the genes therein and the selective forces that have acted to increase their frequency in the population.Implications of the hypothesisCritical interrogation of this hypothesis could serve to underscore the important role of introgression as a source of adaptive alleles and as a driver of evolutionary change, and it would highlight the role of admixture in facilitating rapid human evolution.ReviewersThis article was reviewed by Frank Eisenhaber, Lakshminarayan Iyer and Igor B. Rogozin

Overview of the origins and history of the five major cucurbit crops: issues for ancient DNA analysis of archaeological specimens

The gourd family, Cucurbitaceae, contains five vegetable crops of worldwide importance, the pumpkins and squash (Cucurbita spp.), watermelons (Citrullus lanatus), melons (Cucumis melo) and cucumbers (Cucumis sativus). Here is presented a synopsis of the origin and history of these cucurbit crops. Historical records of the use of cucurbits by people take the form of archaeobotanical finds, iconography and literature. The weight of the evidence indicates that Cucurbita spp. were first cultivated in the Americas at least 10,000 years ago, and that by 1492 ce a number of cultivar-groups of pumpkins and squash had been developed by indigenous American peoples. Watermelons were cultivated in northeastern Africa at least 4,000 years ago, first probably as a source of fresh water. Melons and cucumbers are native to Asia, probably initially cultivated for the use of the young fruits as vegetables. Melons spread to eastern Africa at an early date, but cucumbers are probably a more recent domesticate and spread westwards later, reaching Europe in early medieval times. Sequencing of cucurbit plant genomes and advances in ancient DNA research offer much promise for obtaining an improved assessment of cucurbit crop origins, specifically the genetic constitution and geographical home of ancestral source populations. Next-generation genomic sequencing, if applied to an appropriate array of archaeological cucurbit remains and modern germplasm, could contribute much to the understanding of the history and evolution under domestication of cucurbit crops.

Quantifying the similarity between genes and geography across Alaska's alpine small mammals

AbstractAimQuantitatively evaluate the similarity of genomic variation and geography in five different alpine small mammals in Alaska, and use this quantitative assessment of concordance as a framework for refining hypotheses about the processes structuring population genetic variation in either a species‐specific or shared manner.LocationAlaska and adjacent north‐western Canada.MethodsFor each taxon we generated 3500–7500 single‐nucleotide polymorphisms and applied a Procrustes analysis to find an optimal transformation that maximizes the similarity between principal components analysis maps of genetic variation and geographical maps of sample locations. We generate stability maps using projected distributions from ecological niche models of the Last Glacial Maximum and the present.ResultsSignificant similarity between genes and geography exists across taxa. However, the extent to which geography is predictive of patterns of genetic variation not only differs among taxa, but the correspondence between genes and geography varies over space. Geographical areas where genetic structure aligns poorly with the geographical coordinates are of particular interest because they indicate regions where processes other than isolation by distance (IBD) have influenced genetic variation. The clustering of individuals according to their sample location does not support suppositions of admixture, despite the presumed high vagility of some species (e.g. arctic ground squirrels).Main conclusionsGenomic data indicate a more nuanced biogeographical history for the taxa than suggested by previous studies based on mtDNA alone. These include departures from IBD that are shared among taxa, which suggest some shared processes structuring genetic variation, including new potential ancestral source populations. In addition, some regions fit expectations of IBD where incremental migration and gene flow play a strong role in population structure, despite any ecological difference among taxa. Differences in dispersal capabilities do not result in different species‐specific local patterns of population structure, at least at the sampling scale examined here. We highlight how the general fit to, as well as departures from, expectations for patterns of genetic variation based on the Procrustes analyses can be used to generate hypotheses about the underlying processes.

Ancestry, admixture and fitness in Colombian genomes.

The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%–96.7%), followed by Native American (average = 18.1%, range = 2.1%–33.3%) and African (average = 7.3%, range = 0.2%–38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment.

Microhabitat differences impact phylogeographic concordance of codistributed species: genomic evidence in montane sedges (Carex L.) from the Rocky Mountains.

By selecting codistributed, closely related montane sedges from the Rocky Mountains that are similar in virtually all respects but one-their microhabitat affinities-we test predictions about how patterns of genetic variation are expected to differ between Carex nova, an inhabitant of wetlands, and Carex chalciolepis, an inhabitant of drier meadows, slopes, and ridges. Although contemporary populations of the taxa are similarly isolated, the distribution of glacial moraines suggests that their past population connectedness would have differed. Sampling of codistributed population pairs from different mountain ranges combined with the resolution provided by over 24,000 single nucleotide polymorphism loci supports microhabitat-mediated differences in the sedges' patterns of genetic variation that are consistent with their predicted differences in the degree of isolation of ancestral source populations. Our results highlight how microhabitat preferences may interact with glaciations to produce fundamental differences in the past distributions of presently codistributed species. We discuss the implications of these findings for generalizing the impacts of climate-induced distributional shifts for communities, as well as for the prospects of gaining insights about species-specific deterministic processes, not just deterministic community-level responses, from comparative phylogeographic study.

Increased genetic diversity of ADME genes in African Americans compared with their putative ancestral source populations and implications for pharmacogenomics.

BackgroundAfrican Americans have been treated as a representative population for African ancestry for many purposes, including pharmacogenomic studies. However, the contribution of European ancestry is expected to result in considerable differences in the genetic architecture of African American individuals compared with an African genome. In particular, the genetic admixture influences the genomic diversity of drug metabolism-related genes, and may cause high heterogeneity of drug responses in admixed populations such as African Americans.ResultsThe genomic ancestry information of African-American (ASW) samples was obtained from data of the 1000 Genomes Project, and local ancestral components were also extracted for 32 core genes and 252 extended genes, which are associated with drug absorption, distribution, metabolism, and excretion (ADME) genes. As expected, the global genetic diversity pattern in ASW was determined by the contributions of its putative ancestral source populations, and the whole profiles of ADME genes in ASW are much closer to those in YRI than in CEU. However, we observed much higher diversity in some functionally important ADME genes in ASW than either CEU or YRI, which could be a result of either genetic drift or natural selection, and we identified some signatures of the latter. We analyzed the clinically relevant polymorphic alleles and haplotypes, and found that 28 functional mutations (including 3 missense, 3 splice, and 22 regulator sites) exhibited significantly higher differentiation between the three populations.ConclusionsAnalysis of the genetic diversity of ADME genes showed differentiation between admixed population and its ancestral source populations. In particular, the different genetic diversity between ASW and YRI indicated that the ethnic differences in pharmacogenomic studies are broadly existed despite that African ancestry is dominant in Africans Americans. This study should advance our understanding of the genetic basis of the drug response heterogeneity between populations, especially in the case of population admixture, and have significant implications for evaluating potential inter-population heterogeneity in drug treatment effects.

Autosomal and X-linked single nucleotide polymorphisms reveal a steep Asian–Melanesian ancestry cline in eastern Indonesia and a sex bias in admixture rates

The geographical region between mainland Asia and New Guinea is characterized by numerous small islands with isolated human populations. Phenotypically, groups in the west are similar to their neighbours in mainland Southeast Asia, eastern groups near New Guinea are similar to Melanesians, and intervening populations are intermediate in appearance. A long-standing question is whether this pattern primarily reflects mixing between groups with distinct origins or whether natural selection has shaped this range of variation by acting differentially on populations across the region. To address this question, we genotyped a set of 37 single nucleotide polymorphisms that are evolutionarily independent, putatively neutral and highly informative for Asian-Melanesian ancestry in 1430 individuals from 60 populations spanning mainland Asia to Melanesia. Admixture analysis reveals a sharp transition from Asian to Melanesian genetic variants over a narrow geographical region in eastern Indonesia. Interestingly, this admixture cline roughly corresponds to the human phenotypic boundary noted by Alfred Russell Wallace in 1869. We conclude that this phenotypic gradient probably reflects mixing of two long-separated ancestral source populations-one descended from the initial Melanesian-like inhabitants of the region, and the other related to Asian groups that immigrated during the Paleolithic and/or with the spread of agriculture. A higher frequency of Asian X-linked markers relative to autosomal markers throughout the transition zone suggests that the admixture process was sex-biased, either favouring a westward expansion of patrilocal Melanesian groups or an eastward expansion of matrilocal Asian immigrants. The matrilocal marriage practices that dominated early Austronesian societies may be one factor contributing to this observed sex bias in admixture rates.

Coupling Genetic and Ecological-Niche Models to Examine How Past Population Distributions Contribute to Divergence

Understanding the impact of climate-induced distributional shifts on species divergence, like those accompanying the Pleistocene glacial cycles [1, 2], requires tools that explicitly incorporate the geographic configuration of past distributions into analyses of genetic differentiation. Depending on the historical distribution of species, genetic differences may accumulate among ancestral source populations, but there is long-standing debate whether displacements into glacial refugia promoted divergence. Here we integrate coalescent-based genetic models [3, 4] with ecological-niche modeling [5, 6] to generate expectations for patterns of genetic variation based on an inferred past distribution of a species. Reconstruction of the distribution of a montane grasshopper species during the last glacial maximum suggests that Melanoplus marshalli populations from the sky islands of Colorado and Utah were likely colonized from multiple ancestral source populations. The genetic analyses provide compelling evidence that the historical distribution of M. marshalli-namely, spatial separation of multiple refugia-was conducive to genetic differentiation. The coupling of genetic and ecological-niche modeling provides a new and flexible tool for integrating paleoenvironmental details into species-specific predictions of population structure that can increase our understanding of why the glacial cycles promoted speciation in some taxa and yet inhibited diversification in others [7, 8].

Population structure of Y chromosome SNP haplogroups in the United States and forensic implications for constructing Y chromosome STR databases

A set of 61 Y chromosome single-nucleotide-polymorphisms (Y-SNPs) is typed in a sample of 2517 individuals from 38 populations to infer the geographic origins of Y chromosomes in the United States and to test for paternal admixture among African-, European-, Hispanic-, Asian-, and Native-Americans. All of the samples were previously typed with the 11 core U.S. Y chromosome short tandem repeats (Y-STRs) recommended by SWGDAM, which revealed high levels of among ethnic group variation and low levels of among-population-within-ethnic-group variation. Admixture estimates vary greatly among populations and ethnic groups. The frequencies of non-European (3.4%) and non-Asian (4.5%) Y chromosomes are generally low in European–American and Asian–American populations, respectively. The frequencies of European Y chromosomes in Native-American populations range widely (i.e., 7–89%) and follow a West to East gradient, whereas they are relatively consistent in African–American populations (26.4 ± 8.9%) from different locations. The European (77.8 ± 9.3%) and Native-American (13.7 ± 7.4%) components of the Hispanic paternal gene pool are also relatively constant among geographic regions; however, the African contribution is much higher in the Northeast (10.5 ± 6.4%) than in the Southwest (1.5 ± 0.9%) or Midwest (0%). To test for the effects of inter-ethnic admixture on the structure of Y-STR diversity in the U.S., we perform subtraction analyses in which Y chromosomes inferred to be admixed by Y-SNP analysis are removed from the database and pairwise population differentiation tests are implemented on the remaining Y-STR haplotypes. Results show that low levels of heterogeneity previously observed between pairs of Hispanic-American populations disappear when African-derived chromosomes are removed from the analysis. This is not the case for an unusual sample of European–Americans from New York City when its African-derived chromosomes are removed, or for Native-American populations when European-derived chromosomes are removed. We infer that both inter-ethnic admixture and population structure in ancestral source populations may contribute to fine scale Y-STR heterogeneity within U.S. ethnic groups.