Charting a landmark-driven path forward for population genetics and ancient DNA research in Africa.

Population history-focused DNA and ancient DNA (aDNA) research in Africa has dramatically increased in the past decade, enabling increasingly fine-scale investigations into the continent's past. However, while international interest in human genomics research in Africa grows, major structural barriers limit the ability of African scholars to lead and engage in such research and impede local communities from partnering with researchers and benefitting from research outcomes. Because conversations about research on African people and their past are often held outside Africa and exclude African voices, an important step for African DNA and aDNA research is moving these conversations to the continent. In May 2023 we held the DNAirobi workshop in Nairobi, Kenya and here we synthesize what emerged most prominently in our discussions. We propose an ideal vision for population history-focused DNA and aDNA research in Africa in ten years' time and acknowledge that to realize this future, we need to chart a path connecting a series of "landmarks" that represent points of consensus in our discussions. These include effective communication across multiple audiences, reframed relationships and capacity building, and action toward structural changes that support science and beyond. We concluded there is no single path to creating an equitable and self-sustaining research ecosystem, but rather many possible routes linking these landmarks. Here we share our diverse perspectives as geneticists, anthropologists, archaeologists, museum curators, and educators to articulate challenges and opportunities for African DNA and aDNA research and share an initial map toward a more inclusive and equitable future.

Ancient genomes revealed the complex human interactions of the ancient western Tibetans.

The western Tibetan Plateau is the crossroad between the Tibetan Plateau, Central Asia, and South Asia, and it is a potential human migration pathway connecting these regions. However, the population history of the western Tibetan Plateau remains largely unexplored due to the lack of ancient genomes covering a long-time interval from this area. Here, we reported genome-wide data of 65 individuals dated to 3,500-300 years before present (BP) in the Ngari prefecture. The ancient western Tibetan Plateau populations share the majority of their genetic components with the southern Tibetan Plateau populations and have maintained genetic continuity since 3,500 BP while maintaining interactions with populations within and outside the Tibetan Plateau. Within the Tibetan Plateau, the ancient western Tibetan Plateau populations were influenced by the additional expansion from the south to the southwest plateau before 1,800 BP. Outside the Tibetan Plateau, the western Tibetan Plateau populations interacted with both South and Central Asian populations at least 2,000 years ago, and the South Asian-related genetic influence, despite being very limited, was from the Indus Valley Civilization (IVC) migrants in Central Asia instead of the IVC populations from the Indus Valley. In light of the new genetic data, our study revealed the complex population interconnections across and within the Tibetan Plateau.

Malaria resistance-related biological adaptation and complex evolutionary footprints inferred from one integrative Tai-Kadai-related genomic resource.

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient "Baiyue" tribes.

Genomic and pangenomic analyses provide insights into the population history and genomic diversification of bottle gourd.

Bottle gourd (Lagenaria siceraria (Mol.) Strandl.) is an economically important vegetable crop and one of the earliest domesticated crops. However, the population history and genomic diversification of bottle gourd have not been extensively studied. We generated a comprehensive bottle gourd genome variation map from genome sequences of 197 world-wide representative accessions, which enables a genome-wide association study for identifying genomic loci associated with resistance to zucchini yellow mosaic virus, and constructed a bottle gourd pangenome that harbors 1534 protein-coding genes absent in the reference genome. Demographic analyses uncover that domesticated bottle gourd originated in Southern Africa c. 12 000 yr ago, and subsequently radiated to the New World via the Atlantic drift and to Eurasia through the efforts of early farmers in the initial Holocene. The identified highly differentiated genomic regions among different bottle gourd populations harbor many genes contributing to their local adaptations such as those related to disease resistance and stress tolerance. Presence/absence variation analysis of genes in the pangenome reveals numerous genes including those involved in abiotic/biotic stress responses that have been under selection during the world-wide expansion of bottle gourds. The bottle gourd variation map and pangenome provide valuable resources for future functional studies and genomics-assisted breeding.

Molecular evolution and phylogeographic analysis of wheat dwarf virus.

Wheat dwarf virus (WDV) has caused considerable economic loss in the global production of grain crops. Knowledge of the evolutionary biology and population history of the pathogen remain poorly understood. We performed molecular evolution and worldwide phylodynamic analyses of the virus based on the genes in the protein-coding region of the entire viral genome. Our results showed that host-driven and geography-driven adaptation are major factors that affects the evolution of WDV. Bayesian phylogenetic analysis estimates that the average WDV substitution rate was 4.240 × 10-4 substitutions/site/year (95% credibility interval, 2.828 × 10-4-5.723 × 10-4), and the evolutionary rates of genes encoding proteins with virion-sense transcripts and genes encoding proteins with complementary-sense transcripts were different. The positively selected sites were detected in only two genes encoding proteins with complementary-sense, and WDV-barley are subject to stronger purifying selection than WDV-wheat. The time since the most recent common WDV ancestor was 1746 (95% credibility interval, 1517-1893) CE. Further analyses identified that the WDV-barley population and WDV-wheat population experienced dramatic expansion-decline episodes, and the expansion time of the WDV-barley population was earlier than that of the WDV-wheat population. Our phylogeographic analysis showed that the WDV population originating in Iran was subsequently introduced to Europe, and then spread from Eastern Europe to China.

High-coverage genome of the Tyrolean Iceman reveals unusually high Anatolian farmer ancestry.

The Tyrolean Iceman is known as one of the oldest human glacier mummies, directly dated to 3350-3120 calibrated BCE. A previously published low-coverage genome provided novel insights into European prehistory, despite high present-day DNA contamination. Here, we generate a high-coverage genome with low contamination (15.3×) to gain further insights into the genetic history and phenotype of this individual. Contrary to previous studies, we found no detectable Steppe-related ancestry in the Iceman. Instead, he retained the highest Anatolian-farmer-related ancestry among contemporaneous European populations, indicating a rather isolated Alpine population with limited gene flow from hunter-gatherer-ancestry-related populations. Phenotypic analysis revealed that the Iceman likely had darker skin than present-day Europeans and carried risk alleles associated with male-pattern baldness, type 2 diabetes, and obesity-related metabolic syndrome. These results corroborate phenotypic observations of the preserved mummified body, such as high pigmentation of his skin and the absence of hair on his head.

Genetic adaptations in the population history of Arabidopsis thaliana.

A population encounters a variety of environmental stresses, so the full source of its resilience can only be captured by collecting all the signatures of adaptation to the selection of the local environment in its population history. Based on the multiomic data of Arabidopsis thaliana, we constructed a database of phenotypic adaptations (p-adaptations) and gene expression (e-adaptations) adaptations in the population. Through the enrichment analysis of the identified adaptations, we inferred a likely scenario of adaptation that is consistent with the biological evidence from experimental work. We analyzed the dynamics of the allele frequencies at the 23,880 QTLs of 174 traits and 8,618 eQTLs of 1,829 genes with respect to the total SNPs in the genomes and identified 650 p-adaptations and 3,925 e-adaptations [false discovery rate (FDR) = 0.05]. The population underwent large-scale p-adaptations and e-adaptations along 4 lineages. Extremely cold winters and short summers prolonged seed dormancy and expanded the root system architecture. Low temperatures prolonged the growing season, and low light intensity required the increased chloroplast activity. The subtropical and humid environment enhanced phytohormone signaling pathways in response to the biotic and abiotic stresses. Exposure to heavy metals selected alleles for lower heavy metal uptake from soil, lower growth rate, lower resistance to bacteria, and higher expression of photosynthetic genes were selected. The p-adaptations are directly interpretable, while the coadapted gene expressions reflect the physiological requirements for the adaptation. The integration of this information characterizes when and where the population has experienced environmental stress and how the population responded at the molecular level.

Global molecular evolution and phylogeographic analysis of barley yellow dwarf virus based on the cp and mp genes.

Barley yellow dwarf virus (BYDV) has caused considerable losses in the global production of grain crops such as wheat, barley and maize. We investigated the phylodynamics of the virus by analysing 379 and 485 nucleotide sequences of the genes encoding the coat protein and movement protein, respectively. The maximum clade credibility tree indicated that BYDV-GAV and BYDV-MAV, BYDV-PAV and BYDV-PAS share the same evolutionary lineage, respectively. The diversification of BYDV arises from its adaptability to vector insects and geography. Bayesian phylogenetic analyses showed that the mean substitution rates of the coat and movement proteins of BYDV ranged from 8.327 × 10- 4 (4.700 × 10- 4-1.228 × 10- 3) and 8.671 × 10- 4 (6.143 × 10- 4-1.130 × 10- 3) substitutions/site/year, respectively. The time since the most recent common BYDV ancestor was 1434 (1040-1766) CE (Common Era). The Bayesian skyline plot (BSP) showed that the BYDV population experienced dramatic expansions approximately 8 years into the 21st century, followed by a dramatic decline in less than 15 years. Our phylogeographic analysis showed that the BYDV population originating in the United States was subsequently introduced to Europe, South America, Australia and Asia. The migration pathways of BYDV suggest that the global spread of BYDV is associated with human activities.

Comparative genomics revealed drastic gene difference in two small Chinese perches, Siniperca undulata and S. obscura.

Siniperca undulata and S. obscura (Centrarchiformes: Sinipercidae) are small Chinese perches, living in creeks and streams in southern China. While they have sympatric distribution and occupy similar macrohabitat, their body sizes and ecological niches have many differences. Determining the genome sequences of S. undulata and S. obscura would provide us an essential data set for better understanding their genetic makeup and differences that may play important roles in their adaptation to different niches. We determined the genome sequences of both S. undulata and S. obscura using 10× genomics technology and the next-generation sequencing. The assembled genomes of S. undulata and S. obscura were 744 and 733 Mb, respectively. Gene family analysis revealed that there were no overlap between S. undulata and S. obscura in terms of rapid expanding and rapid contracting genes families, which were related to growth, immunity, and mobility. Positive selection analyses also cooperated that the function of selected genes involve growth, athletic ability, and immunity, which may explain the preference of different niches by S. undulata and S. obscura. Pairwise sequentially Markovian coalescent analyses for the two species suggested that populations of both S. undulata and S. obscura showed a rising trend between 90 and 70 Ka probably due to the mild environment during the last interglacial period. A stage of population shrinking occurred from 70 to 20 Ka, which was in with the Tali glacial period in eastern China (57-16 Ka).

Genome Assembly and Population Sequencing Reveal Three Populations and Signatures of Insecticide Resistance of Tuta absoluta in Latin America.

Tuta absoluta is one of the largest threats to tomato agriculture worldwide. Native to South America, it has rapidly spread throughout Europe, Africa, and Asia over the past two decades. To understand how T. absoluta has been so successful and to improve containment strategies, high-quality genomic resources and an understanding of population history are critical. Here, we describe a highly contiguous annotated genome assembly, as well as a genome-wide population analysis of samples collected across Latin America. The new genome assembly has an L50 of 17 with only 132 contigs. Based on hundreds of thousands of single nucleotide polymorphisms, we detect three major population clusters in Latin America with some evidence of admixture along the Andes Mountain range. Based on coalescent simulations, we find these clusters diverged from each other tens of thousands of generations ago prior to domestication of tomatoes. We further identify several genomic loci with patterns consistent with positive selection and that are related to insecticide resistance, immunity, and metabolism. This data will further future research toward genetic control strategies and inform future containment policies.

Maternal genetic history of ancient Tibetans over the past 4,000 years.

The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity. Here, we reconstruct a 4,000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Tibet. The phylogeny of haplotypes M9a1a, M9a1b, D4g2, G2a'c, and D4i show that ancient Tibetans shared the most recent common ancestor (TMRCA) with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene. In addition, the connections between Tibetans and Northeastern Asians varied over the past 4,000 years, with a stronger matrilineal connection between the two during 4,000-3,000 BP, and a weakened connection after 3,000 BP, that were coincident with climate change, followed by a reinforced connection after the Tubo period (1,400-1,100 BP). Besides, an over 4,000-year matrilineal continuity was observed in some of the maternal lineages. We also found the maternal genetic structure of ancient Tibetans was correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations. Overall, the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that were dynamically shaped by geography, climate changes, as well as historical events.

Evolutionary origin and establishment of a dioecious diploid-tetraploid complex.

Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.

The genetic structure and admixture of Manchus and Koreans in northeast China.

BACKGROUND: The fine-scale genetic profiles and population history of Manchus and Koreans remain unclear. AIM: To infer a fine-scale genetic structure and admixture of Manchu and Korean populations. SUBJECTS AND METHODS: We collected and genotyped 16 Manchus from Liaoning and 18 Koreans from Jilin province with about 700K genome-wide SNPs. We analysed the data using principal component analysis (PCA), ADMIXTURE, Fst, TreeMix, f-statistics, qpWave, and qpAdm. RESULTS: Manchus and Koreans showed a genetic affinity with northern East Asians. Chinese Koreans showed a long-term genetic continuity with Bronze Age populations from the West Liao River and had a strong affinity with Koreans in South Korea and Japan. Manchus had a different genetic profile compared with other Tungusic populations since the Manchus received additional genetic influence from the southern Chinese but didn't have West Eurasian-related admixture. CONCLUSIONS: The genetic formation of Manchus involving southern Chinese was consistent with the extensive interactions between Manchus and populations from central and southern China. The large-scale genetic continuity between ancient West Liao River farmers and Koreans highlighted the role farming expansion played in the peopling of the Korean Peninsula.

Evaluating population histories in Patagonia and Tierra del Fuego, Chile, using ancient mitochondrial and Y-chromosomal DNA.

OBJECTIVES: This study aims to characterize the genetic histories of ancient hunter-gatherer groups in Fuego-Patagonia (Chile) with distinct Marine, Terrestrial, and Mixed Economy subsistence strategies. Mitochondrial (mtDNA) and Y-chromosome data were generated to test three hypotheses. H0: All individuals were drawn from the same panmictic population; H1: Terrestrial groups first populated the region and gave rise to highly specialized Marine groups by ~7,500 cal BP; or H2: Marine and Terrestrial groups represent distinct ancestral lineages who migrated independently into the region. METHODS: Ancient DNA was extracted from the teeth of 50 Fuegian-Patagonian individuals dating from 6,895 cal BP to after European arrival, and analyzed alongside other individuals from previous studies. Individuals were assigned to Marine, Terrestrial, and Mixed Economy groups based on archeological context and stable isotope diet inferences, and mtDNA (HVR1/2) and Y-chromosome variation was analyzed. RESULTS: Endogenous aDNA was obtained from 49/50 (98%) individuals. Haplotype diversities, FST comparisons, and exact tests of population differentiation showed that Marine groups were significantly different from Terrestrial groups based on mtDNA (p < 0.05). No statistically significant differences were found between Terrestrial and Mixed Economy groups. Demographic simulations support models in which Marine groups diverged from the others by ~14,000 cal BP. Y-chromosome results showed similar patterns but were not statistically significant due to small sample sizes and allelic dropout. DISCUSSION: These results support the hypothesis that Marine and Terrestrial economic groups represent distinct ancestral lineages who diverged during the time populations were expanding in the Americas, and may represent independent migrations into Fuego-Patagonia.

MaLAdapt Reveals Novel Targets of Adaptive Introgression From Neanderthals and Denisovans in Worldwide Human Populations.

Adaptive introgression (AI) facilitates local adaptation in a wide range of species. Many state-of-the-art methods detect AI with ad-hoc approaches that identify summary statistic outliers or intersect scans for positive selection with scans for introgressed genomic regions. Although widely used, approaches intersecting outliers are vulnerable to a high false-negative rate as the power of different methods varies, especially for complex introgression events. Moreover, population genetic processes unrelated to AI, such as background selection or heterosis, may create similar genomic signals to AI, compromising the reliability of methods that rely on neutral null distributions. In recent years, machine learning (ML) methods have been increasingly applied to population genetic questions. Here, we present a ML-based method called MaLAdapt for identifying AI loci from genome-wide sequencing data. Using an Extra-Trees Classifier algorithm, our method combines information from a large number of biologically meaningful summary statistics to capture a powerful composite signature of AI across the genome. In contrast to existing methods, MaLAdapt is especially well-powered to detect AI with mild beneficial effects, including selection on standing archaic variation, and is robust to non-AI selective sweeps, heterosis from deleterious mutations, and demographic misspecification. Furthermore, MaLAdapt outperforms existing methods for detecting AI based on the analysis of simulated data and the validation of empirical signals through visual inspection of haplotype patterns. We apply MaLAdapt to the 1000 Genomes Project human genomic data and discover novel AI candidate regions in non-African populations, including genes that are enriched in functionally important biological pathways regulating metabolism and immune responses.

Interpreting mismatches between linguistic and genetic patterns among speakers of Tanimuka (Eastern Tukanoan) and Yukuna (Arawakan).

Northwestern Amazonia is home to a great degree of linguistic diversity, and the human societies in that region are part of complex networks of interaction that predate the arrival of Europeans. This study investigates the population and language contact dynamics between two languages found within this region, Yukuna and Tanimuka, which belong to the Arawakan and Tukanoan language families, respectively. We use evidence from linguistics, ethnohistory, ethnography and population genetics to provide new insights into the contact dynamics between these and other human groups in NWA. Our results show that the interaction between these groups intensified in the last 500 years, to the point that it is difficult to differentiate between them genetically. However, this close interaction has led to more substantial contact-induced language changes in Tanimuka than in Yukuna, consistent with a scenario of language shift and asymmetrical power relations.

Genetic diversity of tick (Acari: Ixodidae) populations and molecular detection of Anaplasma and Ehrlichia infesting beef cattle from upper-northeastern Thailand.

Genetic diversity, genetic structure and demographic history of the ticks infesting beef cattle in Thailand were examined based on mitochondrial cytochrome c oxidase I (cox1) sequences. Tick samples were collected in 12 provinces in upper-northeastern Thailand. Three species were found; Rhipicephalus microplus, R. sanguineus, and Haemaphysalis bispinosa. Of these, R. microplus was by far the most abundant species in beef cattle and was widely distributed throughout the area. No cox1 sequence variation was found in the R. sanguineus or H. bispinosa specimens collected. Low nucleotide diversity but high haplotype diversity was observed in R. microplus. All collected R. microplus specimens belonged to lineage A. Mismatch-distribution analysis, as well as Tajima's D and Fu's Fs tests, provided evidence of recent demographic expansion. A subsample of tick specimens was investigated for presence of Anaplasma and Ehrlichia using a fragment of the 16S rRNA gene. Three species of Anaplasma were detected from R. microplus; Anaplasma marginale (19.08%), Anaplasma platys (1.97%) and unidentified Anaplasma strain (0.66%). The infection rate of Ehrlichia was 7.24% (two ticks were infected with E. minasensis (1.97%) and eight with an unidentified Ehrlichia strain (5.26%). No infections were found in R. sanguineus or H. bispinosa. This is the first report of A. platys and E. minasensis in cattle ticks in Thailand, providing information for future epidemiological surveys and control strategies in this region.

A high-quality chromosome-level genome assembly of Pelteobagrus vachelli provides insights into its environmental adaptation and population history.

Pelteobagrus vachelli is a freshwater fish with high economic value, but the lack of genome resources has severely restricted its industrial development and population conservation. Here, we constructed the first chromosome-level genome assembly of P. vachelli with a total length of approximately 662.13 Mb and a contig N50 was 14.02 Mb, and scaffolds covering 99.79% of the assembly were anchored to 26 chromosomes. Combining the comparative genome results and transcriptome data under environmental stress (high temperature, hypoxia and Edwardsiella. ictaluri infection), the MAPK signaling pathway, PI3K-Akt signaling pathway and apelin signaling pathway play an important role in environmental adaptation of P. vachelli, and these pathways were interconnected by the ErbB family and involved in cell proliferation, differentiation and apoptosis. Population evolution analysis showed that artificial interventions have affected wild populations of P. vachelli. This study provides a useful genomic information for the genetic breeding of P. vachelli, as well as references for further studies on fish biology and evolution.

Population genetic characteristics of Hainan medaka with whole-genome resequencing.

The DMY gene is deleted in all males of the Sanya population (SY-medaka) of the Hainan medaka, Oryzias curvinotus, as recently reported by us. However, due to limited knowledge regarding their population genetic background, it is difficult to explore the possible evolutionary pathway. Herein, we resequenced the whole genome of four populations, including SY-medaka. A total of 56 mitogenomes and 32,826,105 SNPs were identified. We found that the genetic differentiation is highest between SY-medaka and the other populations. The results of the population history of the O. curvinotus suggest that the SY-medaka has been in a bottleneck period recently. Further analysis shows that SY-medaka are the most strongly affected by environmental selection. Moreover, we screened some potential genomic regions, and the genes contained in these regions may explain the potential mechanism of the selection process of the SY-medaka. In conclusion, our study can provide new clues for the adaptation process of medaka in the new environment of Sanya.

Evolving ancient DNA techniques and the future of human history.

Ancient DNA (aDNA) techniques applied to human genomics have significantly advanced in the past decade, enabling large-scale aDNA research, sometimes independent of human remains. This commentary reviews the major milestones of aDNA techniques and explores future directions to expand the scope of aDNA research and insights into present-day human health.