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Nested Admixture During and After the Trans-Atlantic Slave Trade on the Island of São Tomé.

Human genetic admixture, involving the contact between two or more previously isolated populations, can be a complex process influenced by social dynamics. In this study, we aim to reconstruct complex admixture histories in São Tomé, an island in the Gulf of Guinea where the Portuguese established one of the first plantation-based slave societies. Since the 15th century, migration waves from Africa and Europe, slavery, marooning, and indentured labour led to profound demographic shifts and social stratification on the island. Examining 2.5 million SNPs newly genotyped in 96 São Toméans, we observed patterns of genetic differentiation that were more complex than those of other populations descended from enslaved Africans on either side of the Atlantic. Using local ancestry inference and Identical-by-Descent methods, we identified five genetic clusters in São Tomé and reconstructed shared ancestries between each cluster and 70 African and European population samples, including an extensive sample from the Cabo Verde archipelago. Our findings align with historical records, retracing the major slave trade routes and labour-driven migrations after the abolition of slavery. We also identified gene flow between recently admixed groups that were previously isolated on the island. We call this process, creating multiple layers of genetic ancestry in admixed genomes, nested admixture. We suggest that changing social structures in São Tomé transformed the genetic structure of its population and influenced the admixture process. This study demonstrates how successive admixture and isolation events during and after the Trans-Atlantic Slave Trade shaped extant genetic diversity patterns at local scale in Africa.

Humans

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-α-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage

Sex-Biased Admixture Followed by Isolation and Adaptive Evolution Shaped the Genomic and Blood Pressure Diversity of the LopNur People.

The LopNur people are an ethnic group living on the edge of the Taklamakan Desert, and they are believed to demonstrate a unique genetic makeup due to their isolation and limited contact with neighboring populations. However, a lack of genetic studies on the LopNur people has resulted in limited knowledge about their ancestral origins and demographic history. Here, we conducted the first whole-genome sequencing study of 164 LopNur individuals (LOP) to gain insight into their genetic history and adaptive evolution in an isolated desert area. Our analysis revealed that the present-day LOP have experienced a complex history of admixture followed by long-term isolation, with their ancestry derived from East Asia (∼41.46%), West Eurasia (∼26.43%), Siberia (∼24.27%), and South Asia (∼7.82%). Notably, a remarkable sex-biased admixture occurred between Western males and Eastern females. In addition to complex admixture followed by long-term geographic isolation and further recent migrations, adaptive evolution jointly formed the gene pool and phenotypic diversity of the present-day LOP. Intriguingly, our analysis suggests that the USP35-GAB2 region may be correlated with blood pressure in LOP, based on a joint analysis of genomics and blood pressure data. Moreover, we identified two variants, rs7387065, and rs2229437, located on CSMD1 and PRCP, respectively. These variants exhibited frequency differences between Asian and European populations and were reported to be associated with antihypertensive drug absorption. Our results provide new insight into the complex history of the LOP, an admixed and isolated ethnic group residing at the crossroads of East and West, a case with ancient admixture, long-term isolation, adaptive evolution, and sex-biased gene flow.

Female

Deciphering the mosaic genome of sugarcane cultivars through polyploid admixture inference with AdmixPoly.

BACKGROUND: Characterizing population structure and admixture events between ancestral groups plays a key role in understanding the evolutionary history of species and crops. Most tools for inferring admixture have been developed for diploids and are not suitable for polyploids, in particular those with high and mixed ploidy such as Saccharum. RESULTS: Here we present AdmixPoly, an R-package designed to infer admixture in polyploid species both at the genome-wide scale and locally along chromosomes. We compare AdmixPoly with state-of-the-art methods using simulations, demonstrating its precision and computational efficiency. Notably, local admixture inference in complex scenarios, such as high ploidy levels, large numbers of ancestral groups and alleles per marker is enabled through efficient approximations of emission and transition probabilities within a hidden Markov model framework. We apply this approach to characterize the contributions of wild Saccharum species to the complex polyploid genome of modern sugarcane cultivars. A panel of wild and cultivated Saccharum accessions is genotyped for 80K genomic regions, each revealing approximately 50 read-scale haplotypes. CONCLUSIONS: The results reveal that most of the approximately 12 copies of each basic chromosome in modern cultivars are derived from the domesticated species Saccharum officinarum, with one to four copies typically contributed by distinct subgroups of the wild species Saccharum spontaneum. In addition, contributions from an unknown wild Saccharum group originating from the Pacific were identified in most cultivars. The conserved pattern of these introgressions suggests that they can be traced back to the early stages of sugarcane breeding approximately a century ago.

Saccharum

Post-colonial human admixture and natural selection: disentangling signals in complex demographic contexts.

Natural selection and admixture are defining population genetic features of modern human populations, yet their interaction has only recently emerged as a major focus in human evolutionary genomics. While the influence of natural selection on population structure and trait diversity is well established, the ways in which selective pressures operate after admixture have historically received far less attention. In this review, we synthesise the latest progress in understanding post-admixture selection and highlight case studies that illustrate how novel environments, pathogen exposure, dietary shifts and socio-historical transformations have driven genomic adaptation. We conclude by identifying key gaps that remain in the field with the aim of motivating future research and facilitating new insights into how admixture and selection jointly shape human diversity.

Journal Article

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have largely been understudied in medical research due to their complex genetic ancestries. However, the consideration of admixture can help identify ancestry-enriched genetic associations, delineating some of the genetic underpinnings of cross-population phenotypic variation. To this end, we performed local ancestry inference within the All of Us Research Program to identify individuals with recent admixture between African (AFR) and European (EUR) populations (N=48,921). We identified evidence of local AFR ancestry enrichment at the HLA locus, suggestive of putative selection since admixture. Furthermore, we performed the largest admixture mapping (ADM) efforts in AFR-EUR Admixed individuals for 22 traits, identifying 71 associations between inferred local AFR ancestries and a trait. Variants from published GWAS could only account for 18 (25%) of the ADM associations, highlighting novel loci where ancestral haplotypes explained some phenotypic variation. Previous studies likely have not identified these loci due to the low availability of high-powered GWAS in populations genetically similar to AFR. One such loci was 9q21.33, associated with 1.4-fold risk of end-stage kidney disease (ESKD) for carriers of inferred local AFR ancestries at the region. This locus contains the gene SLC28A3, which has previously been linked to kidney function but has never been associated with cross-population ESKD prevalence differences. Together, our results expand upon the existing literature on phenotypic differences between populations, highlighting loci where genetic ancestries play a critical role in the genetic architecture of disease.

Journal Article

Admixture-mapping analysis reveals genetic determinants of the human plasma proteome.

Protein profiling and genetic findings can be integrated to define the genetic architecture of the circulating proteome in chronic diseases. Most self-identified African American (AA) individuals have both African and European genetic ancestry. Admixture mapping can detect genomic association regions in which causal variants exist with substantial differences in allele frequency or effect sizes between genetic ancestries. We performed admixture mapping of the circulating proteome in 1,989 participants from the Jackson Heart Study (JHS), investigating the relation of local African ancestry within genomic regions with levels of circulating proteins. We conditioned protein-local ancestry association models on variants previously found to be associated with those proteins in genome-wide association studies (GWASs). We replicated findings in 196 AA participants from the Multi-Ethnic Study of Atherosclerosis (MESA). 62 proteins were associated with local African ancestry. 21 of 62 remained statistically significant after conditioning on protein-associated variants observed in previous GWASs. 48 of 54 available protein-local ancestry associations were replicated in the MESA. Proteins associated with local African ancestry included chemokines, factors associated with vascular biology and inflammation, and other biologically interesting proteins. Admixture associations unexplained by previously reported protein-associated variants in conditional analysis suggest the existence of causal variants missed by standard GWAS techniques.

Aged

Peruvian Population Genomics: Unraveling the Genetic Landscape and Admixture Dynamics of Urban Populations.

Latin American populations exhibit high genetic and phenotypic diversity shaped by complex admixture histories, yet remain underrepresented in genomic research. Here, we analyze genome-wide data from 432 urban individuals across 13 regions of Peru, including 346 newly genotyped from the Peruvian Genome Project. We revealed fine-scale population structure and demographic patterns shaped by both ancient and recent events. Indigenous American ancestries in urban individuals trace back to ancient north-south interactions consisted with archaeological records, while admixture events occurring within the last 8-10 generations involved sources already admixed between distinct ancestral lineages. Identity-by-descent analyses reveal sustained gene flow in southern Peru, while effective population size trends highlight demographic stability in Lima over the past 25 generations. Sex-biased admixture patterns suggest Indigenous ancestry contribution preferentially mediated by females. These findings offer a comprehensive view of Peru's genetic heritage, advancing our understanding of human genetic diversity and historical demographic processes in Latin America.

Admixture

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N = 48,921). Across 22 traits, we identified 71 ancestry-trait associations, including loci where ancestral haplotypes explained phenotypic variation yet were missed by single-variant association testing due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries are associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in explaining differences between populations. Together, our results expand upon the phenotypic differences between populations and characterize loci where genetic ancestries play a critical role in the architecture of disease.

Humans

Admixture and Selection Driven by El Niño-Southern Oscillation Events Shape the Genetic Structure of Octopus mimus-O. hubbsorum Complex Across the Humboldt and South Equatorial Current Transition Zone.

Marine transition zones, where contrasting water masses converge, can function as natural laboratories for studying admixture and early stages of speciation. The genomic structure of the eastern Pacific Octopus mimus-O. hubbsorum complex was investigated by analyzing whole-genome sequencing data from 67 individuals sampled along the west coast of the Americas, spanning Mexico and the Peruvian coast. This includes the South Equatorial Current, the transition zone, and the Humboldt Current System. The mitochondrial genomes fell into two major genetic clades that largely corresponded to the warm-water northern (O. hubbsorum) and cold-water southern (O. mimus) lineages. Analyses of the nuclear genomes revealed the same bipartite structure but also identified a broad admixture zone characterized by two different admixed clades (Admixed-Cold and Admixed-Warm). The results suggest that episodic relaxation of oceanographic barriers during El Niño-Southern Oscillation (ENSO) events promotes secondary contact and gene flow, resulting in admixed individuals recurrently during ENSO years. However, the survival of these admixed individuals depends on the adaptive genetic composition of each organism and the prevailing environmental conditions. Outlier SNP analysis supports these findings, where the Admixed-Cold cluster shares mainly the adaptive genetic component identified as outliers in O. mimus, while Admixed-Warm is linked to those in O. hubbsorum. The O. mimus-O. hubbsorum complex is currently occupying a gray zone of speciation, in which selection and climate-driven connectivity act in tandem to shape genomic divergence.

gene flow

HAP-SAMPLE2: data-based resampling for association studies with admixture.

MOTIVATION: HAP-SAMPLE2 extends the functionality of the original HAP-SAMPLE tool for simulating genotype-phenotype data, now with features to handle population admixture and rare variant analysis. It allows users to define parameters such as disease prevalence and allele effect sizes for both common and rare variant simulations. RESULTS: HAP-SAMPLE2 provides an efficient means for simulating complex datasets, suitable for large-scale projects like the 1000 Genomes Project. Its capabilities for population admixture allow users to create admixed populations or preserve substructures while introducing novel variation through artificial recombination. Additionally, the tool supports burden testing for rare variants using fixed and Madsen-Browning weighting schemes. AVAILABILITY AND IMPLEMENTATION: The software, along with a detailed vignette, is available on GitHub: https://github.com/M3dical/HAPSAMPLE2.

Software

Ancestry, admixture, and pathogens in contemporaneous Neolithic farmers and foragers on the Island of Gotland.

Two archaeological cultural complexes; the Neolithic Funnelbeaker culture (FBC) and the Pitted ware culture (PWC), coexisted on Gotland for over 500 years, between ~3300 and 2800 calBCE. The ancestry of the FBC farmers and PWC marine foragers largely aligns with European Neolithic Farmers and European Mesolithic foragers, respectively, but the direct interactions between the groups on Gotland is not understood. We present a Middle Neolithic (MN) high-coverage genome and a Late Neolithic (LN) low-coverage genome from the Ansarve FBC dolmen. We investigate ancestry, admixture, and pathogens among these MN farmers (n = 6), foragers (n = 19), and the LN individual. We find that recent gene-flow between farmers and foragers could have taken place, although most gene-flow happened prior to their coexistence on the island. We also find evidence of different Yersinia pestis strains in the three cultural groups, showing that the pestis was widespread among groups with different subsistence strategies.

Humans

Admixture Mapping Reveals Evidence for Multiple Mitonuclear Incompatibilities in Swordtail Fish Hybrids.

How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish (Xiphophorus) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridising species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.

Animals

Genomic consequences of admixture in an experimentally founded sand lizard population.

Conservation interventions are increasingly required for species threatened by population declines and isolation due to anthropogenic pressures. Small, isolated populations are particularly vulnerable to the loss of genetic diversity, increased inbreeding, and the accumulation of deleterious mutations. Translocations or supplementation of allopatric individuals for genetic rescue may be the only way to increase genetic diversity and increase population persistence via increased adaptive potential. Here, we use an experimentally admixed population of sand lizards on a small island in Sweden as a valuable model of genetic rescue. This population was established approximately 20 years ago (5-6 generations), resulting in increased fecundity and hatchling viability. This population was founded from crossings between individuals from an inbred population from the nearby mainland and individuals sourced from populations in southern Sweden. Low-coverage whole-genome sequencing revealed elevated genetic diversity and reduced realized genetic load in this admixed population relative to the source populations. Ancestry analyses indicated a greater contribution of southern Swedish genetic variation, potentially reflecting the contribution of beneficial adaptive variation from this region that may underlie the positive population effects. This system provides valuable empirical insights into the long-term genomic consequences of genetic rescue in this model vertebrate population.

Journal Article

An archaic reference-free method to jointly infer Neanderthal and Denisovan introgressed segments in modern human genomes.

Admixture between populations is a common feature of human history. Admixture events introduce new genetic variation that can fuel evolution. Characterizing the significance of admixture events on the evolution of populations across various species is of great interest to evolutionary geneticists. Local Ancestry Inference (LAI) methods infer genetic ancestry of an individual at a particular chromosomal location. Certain methods specialize in detecting archaic introgression, which consists of interbreeding between modern and archaic humans like Neanderthals and Denisovans. Most current LAI methods allow the detection of a single archaic ancestry, and post-processing may distinguish between multiple waves of introgression. These methods vary in how they choose archaic or modern reference genomes for the inference. Here, we present a new HMM-based method (DAIseg), which has the advantage of simultaneously distinguishing between multiple waves of ancient and recent admixture, using only modern human reference genomes. Simulations demonstrate that DAIseg achieves higher overall performance than state-of-the-art methods. We also apply DAIseg to Papuan populations to jointly detect Denisovan and Neanderthal introgressed segments, and identify a higher number of archaic segments than previous methods. Analysis of inferred introgressed segments, shows that we can identify evidence for two Denisovan introgression events in Papuans. Overall, on top of being able to deal with both Archaic and recent admixture, DAIseg provides a more principled approach for detecting and classifying Denisovan and Neanderthal segments which will improve downstream analysis of introgressed segments to infer the impact of archaic introgression in humans.

Denisovan

Largest-Scale Genomic Resource Reconstructing the Genetic Origin, Population Structure, and Biological Adaptations of the Hui People.

Historical and archaeological records indicate that the Maritime and Land Silk Roads played a pivotal role in facilitating Trans-Eurasian migrations and cultural exchanges. However, the extent to which population movements or the spread of ideas shape Chinese Hui populations remains debated. We present the largest genomic resource to date, including 2,280 Hui individuals sequenced or genotyped from 30 diverse regions, to examine the genetic origins, population structure, and biological adaptations of this underrepresented group in global human genome research. We identified a detailed population structure characterized by five distinct genetic lineages of the Hui, influenced by geography and varying gene flow. The admixture history and demographic events suggest that the northwestern and northern Hui lineages emerged from demic diffusion during the Tang and Yuan Dynasties via the Land Silk Road. In contrast, the southern and island Hui lineages reflect cultural diffusion along the Maritime Silk Road, while the mixed southern-northern lineage likely developed through a combination of demic and cultural diffusion. Our findings support a hybrid model for Hui formation, indicating that both demographic processes and sociocultural transmissions contributed to their population history. We identified east-west highly differentiated variants and pre- and post-admixture adaptations in Hui genomes, demonstrating that admixture-driven adaptive or neutral variants impacted susceptibility to cardiovascular diseases and immune- and diet-related traits. These adaptive signatures include post-admixture signals of SLC24A5 and ECHDC1 in the Hui, as well as pre-admixture signals of the HLA region, BCL2A1, and KCNH8 in the East Asian source. Overall, our study suggests that Han-related genetic components helped the Hui population rapidly adapt to new local environments. Additionally, the frequency spectrum of clinically essential variants differed significantly between Hui and Han individuals, emphasizing the importance of including underrepresented populations in genomic research to promote health equity.

Humans

Genome-Wide SNP Characterisation of Three Kazakh Sheep Breeds: Kazakh Fat-Tailed Coarse-Wool, Degeres, and Etti Merino.

Kazakhstan's sheep portfolio underpins much of the country's mutton and wool production, yet several of its principal breeds remain genomically uncharacterised. The aim of this study was to characterise the genomic diversity, population structure, and global phylogenetic placement of three economically important Kazakh breeds and to determine whether they constitute separate gene pools requiring independent management. We present the first genome-wide SNP characterisation to include the Degeres (DE), the Etti Merino (EM), and the Kazakh fat-tailed coarse-wool (KKG) breeds simultaneously. A total of 1497 animals (DE = 354, EM = 642, KKG = 501) sampled across seven production households were genotyped and, after quality control, analysed at 42,279 SNPs, of which 22,766 LD-pruned markers were used for principal component analysis and AMOVA. We applied principal component analysis (PCA), pairwise FST, analysis of molecular variance (AMOVA), neighbour-joining phylogenetics, model-based ancestry estimation (ADMIXTURE), and Hill-number diversity profiling, and projected the breeds against the global Ovine SNP50 HapMap panel (74 reference breeds, 2819 animals; 37,685 shared SNPs). All three breeds retained uniformly high within-breed diversity (expected heterozygosity 0.413-0.417) with fixation indices at or near zero. AMOVA partitioned 94.03% of variance within breeds (&#x3a6;ST = 0.060, p < 0.001). PCA, phylogeny, and ADMIXTURE concordantly resolved three breed-specific clusters at K = 3, with a maximum interbreed FST of 0.038 within the study dataset. Against the global panel, EM was genetically closest to Merino and Merino-derived reference breeds (pooled FST = 0.017) and substantially more distant from Southwest Asian sheep (FST = 0.045), whereas DE and KKG showed the reciprocal pattern (FST = 0.027 and 0.020 to Southwest Asia, 0.052 to the Merino group). DE additionally displayed the heterozygote excess and partial admixture expected of an incompletely consolidated composite. These results delineate three distinct gene pools and carry direct implications for breed management and the conservation of genomic diversity in Kazakhstani sheep.

ADMIXTURE

Local ancestry inference identifies robust evidence of selection in Neolithic Europe.

During the European Neolithic, migrating Anatolian farmers admixed with local hunter-gatherers, coinciding with major shifts in diet, environment, and lifestyle that imposed strong selective pressures. Local ancestry inference is widely used to detect selection following admixture, but most methods were developed and validated on present-day populations. Their performance in ancient DNA - where reference panels are smaller, data are sparser, and admixture is more ancient - remains unresolved. We benchmark eight local ancestry inference methods on 176 imputed Neolithic genomes. While individual-level ancestry estimates are highly correlated across methods, inferred tract lengths and admixture time estimates vary by an order of magnitude. Overall, we recommend Gnomix or RFMix for general use. We also investigated our ability to detect natural selection using LAI. Integrating results across methods and replicating across methods and in two independent datasets (n=378 and 1,121) we identify a robust ancestry deviation at FADS1/2, consistent with adaptation on metabolism. We also identify IRAK4 (innate immunity) as a candidate locus, but with less consistent signal across methods. Finally, we replicate previous reports of excess hunter-gatherer ancestry at the HLA, but these results are inconsistent across methods and suggest that they may be affected by bias in local ancestry inference. Our findings demonstrate that while local ancestry inference recovers biologically meaningful signals in ancient genomes, results can be sensitive to the methods used for inference, particularly in complex regions like the HLA. Method choice critically influences inferred ancestry patterns and selection signals, underscoring the importance of multi-method validation.

Journal Article