The genetic legacy of the expansion of Bantu-speaking peoples in Africa.

The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent1-7. With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8. We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.

The ancestry and geographical origins of St Helena's liberated Africans.

The island of St Helena played a crucial role in the suppression of the transatlantic slave trade. Strategically located in the middle of the South Atlantic, it served as a staging post for the Royal Navy and reception point for enslaved Africans who had been "liberated" from slave ships intercepted by the British. In total, St Helena received approximately 27,000 liberated Africans between 1840 and 1867. Written sources suggest that the majority of these individuals came from West Central Africa, but their precise origins are unknown. Here, we report the results of ancient DNA analyses that we conducted as part of a wider effort to commemorate St Helena's liberated Africans and to restore knowledge of their lives and experiences. We generated partial genomes (0.1-0.5×) for 20 individuals whose remains had been recovered during archaeological excavations on the island. We compared their genomes with genotype data for over 3,000 present-day individuals from 90 populations across sub-Saharan Africa and conclude that the individuals most likely originated from different source populations within the general area between northern Angola and Gabon. We also find that the majority (17/20) of the individuals were male, supporting a well-documented sex bias in the latter phase of the transatlantic slave trade. The study expands our understanding of St Helena's liberated African community and illustrates how ancient DNA analyses can be used to investigate the origins and identities of individuals whose lives were bound up in the story of slavery and its abolition.

A genetic and linguistic analysis of the admixture histories of the islands of Cabo Verde.

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals' birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants' genomic diversity and structure on both sides of the Atlantic.

A Population Genetic Perspective on Subsistence Systems in the Sahel/Savannah Belt of Africa and the Historical Role of Pastoralism.

This review focuses on the Sahel/Savannah belt, a large region of Africa where two alternative subsistence systems (pastoralism and agriculture), nowadays, interact. It is a long-standing question whether the pastoralists became isolated here from other populations after cattle began to spread into Africa (~8 thousand years ago, kya) or, rather, began to merge with other populations, such as agropastoralists, after the domestication of sorghum and pearl millet (~5 kya) and with the subsequent spread of agriculture. If we look at lactase persistence, a trait closely associated with pastoral lifestyle, we see that its variants in current pastoralists distinguish them from their farmer neighbours. Most other (mostly neutral) genetic polymorphisms do not, however, indicate such clear differentiation between these groups; they suggest a common origin and/or an extensive gene flow. Genetic affinity and ecological symbiosis between the two subsistence systems can help us better understand the population history of this African region. In this review, we show that genomic datasets of modern Sahel/Savannah belt populations properly collected in local populations can complement the still insufficient archaeological research of this region, especially when dealing with the prehistory of mobile populations with perishable material culture and therefore precarious archaeological visibility.

The loss of biodiversity in Madagascar is contemporaneous with major demographic events.

Only 400 km off the coast of East Africa, the island of Madagascar is one of the last large land masses to have been colonized by humans. While many questions surround the human occupation of Madagascar, recent studies raise the question of human impact on endemic biodiversity and landscape transformation. Previous genetic and linguistic analyses have shown that the Malagasy population has emerged from an admixture that happened during the last millennium, between Bantu-speaking African populations and Austronesian-speaking Asian populations. By studying the sharing of chromosome segments between individuals (IBD determination), local ancestry information, and simulated genetic data, we inferred that the Malagasy ancestral Asian population was isolated for more than 1,000 years with an effective size of just a few hundred individuals. This isolation ended around 1,000 years before present (BP) by admixture with a small African population. Around the admixture time, there was a rapid demographic expansion due to intrinsic population growth of the newly admixed population, which coincides with extensive changes in Madagascar's landscape and the extinction of all endemic large-bodied vertebrates. Therefore, our approach can provide new insights into past human demography and associated impacts on ecosystems.

Demographic and Selection Histories of Populations Across the Sahel/Savannah Belt.

The Sahel/Savannah belt harbors diverse populations with different demographic histories and different subsistence patterns. However, populations from this large African region are notably under-represented in genomic research. To investigate the population structure and adaptation history of populations from the Sahel/Savannah space, we generated dense genome-wide genotype data of 327 individuals-comprising 14 ethnolinguistic groups, including 10 previously unsampled populations. Our results highlight fine-scale population structure and complex patterns of admixture, particularly in Fulani groups and Arabic-speaking populations. Among all studied Sahelian populations, only the Rashaayda Arabic-speaking population from eastern Sudan shows a lack of gene flow from African groups, which is consistent with the short history of this population in the African continent. They are recent migrants from Saudi Arabia with evidence of strong genetic isolation during the last few generations and a strong demographic bottleneck. This population also presents a strong selection signal in a genomic region around the CNR1 gene associated with substance dependence and chronic stress. In Western Sahelian populations, signatures of selection were detected in several other genetic regions, including pathways associated with lactase persistence, immune response, and malaria resistance. Taken together, these findings refine our current knowledge of genetic diversity, population structure, migration, admixture and adaptation of human populations in the Sahel/Savannah belt and contribute to our understanding of human history and health.

Genetic substructure and complex demographic history of South African Bantu speakers.

South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ~400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.

Population collapse in Congo rainforest from 400 CE urges reassessment of the Bantu Expansion.

The present-day distribution of Bantu languages is commonly thought to reflect the early stages of the Bantu Expansion, the greatest migration event in African prehistory. Using 1149 radiocarbon dates linked to 115 pottery styles recovered from 726 sites throughout the Congo rainforest and adjacent areas, we show that this is not the case. Two periods of more intense human activity, each consisting of an expansion phase with widespread pottery styles and a regionalization phase with many more local pottery styles, are separated by a widespread population collapse between 400 and 600 CE followed by major resettlement centuries later. Coinciding with wetter climatic conditions, the collapse was possibly promoted by a prolonged epidemic. Comparison of our data with genetic and linguistic evidence further supports a spread-over-spread model for the dispersal of Bantu speakers and their languages.

Complex genetic admixture histories reconstructed with Approximate Bayesian Computation.

Admixture is a fundamental evolutionary process that has influenced genetic patterns in numerous species. Maximum-likelihood approaches based on allele frequencies and linkage-disequilibrium have been extensively used to infer admixture processes from genome-wide data sets, mostly in human populations. Nevertheless, complex admixture histories, beyond one or two pulses of admixture, remain methodologically challenging to reconstruct. We developed an Approximate Bayesian Computation (ABC) framework to reconstruct highly complex admixture histories from independent genetic markers. We built the software package MetHis to simulate independent SNPs or microsatellites in a two-way admixed population for scenarios with multiple admixture pulses, monotonically decreasing or increasing recurring admixture, or combinations of these scenarios. MetHis allows users to draw model-parameter values from prior distributions set by the user, and, for each simulation, MetHis can calculate numerous summary statistics describing genetic diversity patterns and moments of the distribution of individual admixture fractions. We coupled MetHis with existing machine-learning ABC algorithms and investigated the admixture history of admixed populations. Results showed that random forest ABC scenario-choice could accurately distinguish among most complex admixture scenarios, and errors were mainly found in regions of the parameter space where scenarios were highly nested, and, thus, biologically similar. We focused on African American and Barbadian populations as two study-cases. We found that neural network ABC posterior parameter estimation was accurate and reasonably conservative under complex admixture scenarios. For both admixed populations, we found that monotonically decreasing contributions over time, from Europe and Africa, explained the observed data more accurately than multiple admixture pulses. This approach will allow for reconstructing detailed admixture histories when maximum-likelihood methods are intractable.

Identification of ancestry proportions in admixed groups across the Americas using clinical pharmacogenomic SNP panels.

We evaluated the performance of three PGx panels to estimate biogeographical ancestry: the DMET panel, and the VIP and Preemptive PGx panels described in the literature. Our analysis indicate that the three panels capture quite well the individual variation in admixture proportions observed in recently admixed populations throughout the Americas, with the Preemptive PGx and DMET panels performing better than the VIP panel. We show that these panels provide reliable information about biogeographic ancestry and can be used to guide the implementation of PGx clinical decision-support (CDS) tools. We also report that using these panels it is possible to control for the effects of population stratification in association studies in recently admixed populations, as exemplified with a warfarin dosing GWA study in a sample from Brazil.

Anthropological genetics perspectives on the transatlantic slave trade.

During the Trans-Atlantic Slave Trade (TAST), around twelve million Africans were enslaved and forcibly moved from Africa to the Americas and Europe, durably influencing the genetic and cultural landscape of a large part of humanity since the 15th century. Following historians, archaeologists, and anthropologists, population geneticists have, since the 1950's mainly, extensively investigated the genetic diversity of populations on both sides of the Atlantic. These studies shed new lights into the largely unknown genetic origins of numerous enslaved-African descendant communities in the Americas, by inferring their genetic relationships with extant African, European, and Native American populations. Furthermore, exploring genome-wide data with novel statistical and bioinformatics methods, population geneticists have been increasingly able to infer the last 500 years of admixture histories of these populations. These inferences have highlighted the diversity of histories experienced by enslaved-African descendants, and the complex influences of socioeconomic, political, and historical contexts on human genetic diversity patterns during and after the slave trade. Finally, the recent advances of paleogenomics unveiled crucial aspects of the life and health of the first generation of enslaved-Africans in the Americas. Altogether, human population genetics approaches in the genomic and paleogenomic era need to be coupled with history, archaeology, anthropology, and demography in interdisciplinary research, to reconstruct the multifaceted and largely unknown history of the TAST and its influence on human biological and cultural diversities today. Here, we review anthropological genomics studies published over the past 15 years and focusing on the history of enslaved-African descendant populations in the Americas.

Closing the Gaps in Genomic Research.

Despite Africa's central role in the origin of our species, our knowledge of the genomic diversity in Africa is remarkably sparse. A recent publication by Choudhury et al. underscores the scientific imperative for a broader characterisation of African genomic diversity to better understand demographic history and improve global human health.

Demographic history and admixture dynamics in African Sahelian populations.

The Sahel/Savannah belt of Africa is a contact zone between two subsistence systems (nomadic pastoralism and sedentary farming) and of two groups of populations, namely Eurasians penetrating from northern Africa southwards and sub-Saharan Africans migrating northwards. Because pastoralism is characterized by a high degree of mobility, it leaves few significant archaeological traces. Demographic history seen through the lens of population genetic studies complements our historical and archaeological knowledge in this African region. In this review, we highlight recent advances in our understanding of demographic history in the Sahel/Savannah belt as revealed by genetic studies. We show the impact of food-producing subsistence strategies on population structure and the somewhat different migration patterns in the western and eastern part of the region. Genomic studies show that the gene pool of various groups of Sahelians consists in a complex mosaic of several ancestries. We also touch upon various signals of genetic adaptations such as lactase persistence, taste sensitivity and malaria resistance, all of which have different distribution patterns among Sahelian populations. Overall, genetic studies contribute to gain a deeper understanding about the demographic and adaptive history of human populations in this specific African region and beyond.

Predicting haplogroups using a versatile machine learning program (PredYMaLe) on a new mutationally balanced 32 Y-STR multiplex (CombYplex): Unlocking the full potential of the human STR mutation rate spectrum to estimate forensic parameters.

We developed a new mutationally well-balanced 32 Y-STR multiplex (CombYplex) together with a machine learning (ML) program PredYMaLe to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, PredYMaLe was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %). We observe heterogeneity in haplogroup assignation accuracy among classes, with most haplogroups having high prediction scores (99-100 %) and two (E1b1b and G) having lower scores (67 %). The small sample sizes of these classes explain the high tendency to misclassify the Y-profiles of these haplogroups; results were measurably improved as soon as more training data were added. We provide evidence that our ML approach is a robust method to accurately predict haplogroups when it is combined with a sufficient number of markers, well-balanced mutation rate Y-STR panels, and large ML training sets. Further research on confounding factors (such as CNV-STR or gene conversion) and ideal STR panels in regard to the branches analysed can be developed to help classifiers further optimize prediction scores.

Novel insights on demographic history of tribal and caste groups from West Maharashtra (India) using genome-wide data.

The South Asian subcontinent is characterized by a complex history of human migrations and population interactions. In this study, we used genome-wide data to provide novel insights on the demographic history and population relationships of six Indo-European populations from the Indian State of West Maharashtra. The samples correspond to two castes (Deshastha Brahmins and Kunbi Marathas) and four tribal groups (Kokana, Warli, Bhil and Pawara). We show that tribal groups have had much smaller effective population sizes than castes, and that genetic drift has had a higher impact in tribal populations. We also show clear affinities between the Bhil and Pawara tribes, and to a lesser extent, between the Warli and Kokana tribes. Our comparisons with available modern and ancient DNA datasets from South Asia indicate that the Brahmin caste has higher Ancient Iranian and Steppe pastoralist contributions than the Kunbi Marathas caste. Additionally, in contrast to the two castes, tribal groups have very high Ancient Ancestral South Indian (AASI) contributions. Indo-European tribal groups tend to have higher Steppe contributions than Dravidian tribal groups, providing further support for the hypothesis that Steppe pastoralists were the source of Indo-European languages in South Asia, as well as Europe.

Along the Indian Ocean Coast: Genomic Variation in Mozambique Provides New Insights into the Bantu Expansion.

The Bantu expansion, which started in West Central Africa around 5,000 BP, constitutes a major migratory movement involving the joint spread of peoples and languages across sub-Saharan Africa. Despite the rich linguistic and archaeological evidence available, the genetic relationships between different Bantu-speaking populations and the migratory routes they followed during various phases of the expansion remain poorly understood. Here, we analyze the genetic profiles of southwestern and southeastern Bantu-speaking peoples located at the edges of the Bantu expansion by generating genome-wide data for 200 individuals from 12 Mozambican and 3 Angolan populations using ∼1.9 million autosomal single nucleotide polymorphisms. Incorporating a wide range of available genetic data, our analyses confirm previous results favoring a "late split" between West and East Bantu speakers, following a joint passage through the rainforest. In addition, we find that Bantu speakers from eastern Africa display genetic substructure, with Mozambican populations forming a gradient of relatedness along a North-South cline stretching from the coastal border between Kenya and Tanzania to South Africa. This gradient is further associated with a southward increase in genetic homogeneity, and involved minimum admixture with resident populations. Together, our results provide the first genetic evidence in support of a rapid North-South dispersal of Bantu peoples along the Indian Ocean Coast, as inferred from the distribution and antiquity of Early Iron Age assemblages associated with the Kwale archaeological tradition.

Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.

BACKGROUND: Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations. RESULTS: We present a GWAS of skin pigmentation in an admixed sample from Cuba (N = 762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N = 2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response. CONCLUSIONS: Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.

Exploring Cuba's population structure and demographic history using genome-wide data.

Cuba is the most populated country in the Caribbean and has a rich and heterogeneous genetic heritage. Here, we take advantage of dense genomic data from 860 Cuban individuals to reconstruct the genetic structure and ancestral origins of this population. We found distinct admixture patterns between and within the Cuban provinces. Eastern provinces have higher African and Native American ancestry contributions (average 26% and 10%, respectively) than the rest of the Cuban provinces (average 17% and 5%, respectively). Furthermore, in the Eastern Cuban region, we identified more intense sex-specific admixture patterns, strongly biased towards European male and African/Native American female ancestries. Our subcontinental ancestry analyses in Cuba highlight the Iberian population as the best proxy European source population, South American and Mesoamerican populations as the closest Native American ancestral component, and populations from West Central and Central Africa as the best proxy sources of the African ancestral component. Finally, we found complex admixture processes involving two migration pulses from both Native American and African sources. Most of the inferred Native American admixture events happened early during the Cuban colonial period, whereas the African admixture took place during the slave trade and more recently as a probable result of large-scale migrations from Haiti.