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.

A Dynamic 6,000-Year Genetic History of Eurasia's Eastern Steppe.

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the region's population history. Here, we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

Genomic History of Neolithic to Bronze Age Anatolia, Northern Levant, and Southern Caucasus.

Here, we report genome-wide data analyses from 110 ancient Near Eastern individuals spanning the Late Neolithic to Late Bronze Age, a period characterized by intense interregional interactions for the Near East. We find that 6th millennium BCE populations of North/Central Anatolia and the Southern Caucasus shared mixed ancestry on a genetic cline that formed during the Neolithic between Western Anatolia and regions in today's Southern Caucasus/Zagros. During the Late Chalcolithic and/or the Early Bronze Age, more than half of the Northern Levantine gene pool was replaced, while in the rest of Anatolia and the Southern Caucasus, we document genetic continuity with only transient gene flow. Additionally, we reveal a genetically distinct individual within the Late Bronze Age Northern Levant. Overall, our study uncovers multiple scales of population dynamics through time, from extensive admixture during the Neolithic period to long-distance mobility within the globalized societies of the Late Bronze Age. VIDEO ABSTRACT.

Reconstructing Prehistoric African Population Structure.

We assembled genome-wide data from 16 prehistoric Africans. We show that the anciently divergent lineage that comprises the primary ancestry of the southern African San had a wider distribution in the past, contributing approximately two-thirds of the ancestry of Malawi hunter-gatherers ∼8,100-2,500 years ago and approximately one-third of the ancestry of Tanzanian hunter-gatherers ∼1,400 years ago. We document how the spread of farmers from western Africa involved complete replacement of local hunter-gatherers in some regions, and we track the spread of herders by showing that the population of a ∼3,100-year-old pastoralist from Tanzania contributed ancestry to people from northeastern to southern Africa, including a ∼1,200-year-old southern African pastoralist. The deepest diversifications of African lineages were complex, involving either repeated gene flow among geographically disparate groups or a lineage more deeply diverging than that of the San contributing more to some western African populations than to others. We finally leverage ancient genomes to document episodes of natural selection in southern African populations. PAPERCLIP.

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.

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.

Negative selection on complex traits limits phenotype prediction accuracy between populations.

Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and negative selection on complex traits can result in population-specific genetic architectures. For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such a model, individuals in the tails of the genetic risk distribution may not be identified via polygenic scores generated in another population. We empirically test these predictions by building a model to stratify heritability between European-specific and shared variants and applied it to 37 traits and diseases in the UK Biobank. Across these phenotypes, ∼30% of the heritability comes from European-specific variants. We conclude that genetic association studies need to include more diverse populations to enable the utility of phenotype prediction in all populations.

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.

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.

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.

Genetic evidence of tri-genealogy hypothesis on the origin of ethnic minorities in Yunnan.

BACKGROUND: Yunnan is located in Southwest China and consists of great cultural, linguistic, and genetic diversity. However, the genomic diversity of ethnic minorities in Yunnan is largely under-investigated. To gain insights into population history and local adaptation of Yunnan minorities, we analyzed 242 whole-exome sequencing data with high coverage (~ 100-150 ×) of Yunnan minorities representing Achang, Jingpo, Dai, and Deang, who were linguistically assumed to be derived from three ancient lineages (the tri-genealogy hypothesis), i.e., Di-Qiang, Bai-Yue, and Bai-Pu. RESULTS: Yunnan minorities show considerable genetic differences. Di-Qiang populations likely migrated from the Tibetan area about 6700 years ago. Genetic divergence between Bai-Yue and Di-Qiang was estimated to be 7000 years, and that between Bai-Yue and Bai-Pu was estimated to be 5500 years. Bai-Pu is relatively isolated, but gene flow from surrounding Di-Qiang and Bai-Yue populations was also found. Furthermore, we identified genetic variants that are differentiated within Yunnan minorities possibly due to the living circumstances and habits. Notably, we found that adaptive variants related to malaria and glucose metabolism suggest the adaptation to thalassemia and G6PD deficiency resulting from malaria resistance in the Dai population. CONCLUSIONS: We provided genetic evidence of the tri-genealogy hypothesis as well as new insights into the genetic history and local adaptation of the Yunnan minorities.

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.

The Euscaphis japonica genome and the evolution of malvids.

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.

Horse Paleogenomes and Human-Animal Interactions in Prehistory.

A new analysis of paleogenomic data from 278 ancient horses (Fages et al. Cellhttp://doi.org/10.1016/j.cell.2019.03.049) finds that this animal - crucially important to many ancient and contemporary human societies for subsistence, transportation, conflict, and more - was domesticated in at least two different regions, but with the geographic and cultural origins of the modern domestic horse lineage remaining unknown. By tracing ancient horse population movements and inferring the spatiotemporal trajectories of phenotypic adaptations, this study provides fresh perspectives on past human group interactions and activities.

A Transient Pulse of Genetic Admixture from the Crusaders in the Near East Identified from Ancient Genome Sequences.

During the medieval period, hundreds of thousands of Europeans migrated to the Near East to take part in the Crusades, and many of them settled in the newly established Christian states along the Eastern Mediterranean coast. Here, we present a genetic snapshot of these events and their aftermath by sequencing the whole genomes of 13 individuals who lived in what is today known as Lebanon between the 3rd and 13th centuries CE. These include nine individuals from the "Crusaders' pit" in Sidon, a mass burial in South Lebanon identified from the archaeology as the grave of Crusaders killed during a battle in the 13th century CE. We show that all of the Crusaders' pit individuals were males; some were Western Europeans from diverse origins, some were locals (genetically indistinguishable from present-day Lebanese), and two individuals were a mixture of European and Near Eastern ancestries, providing direct evidence that the Crusaders admixed with the local population. However, these mixtures appear to have had limited genetic consequences since signals of admixture with Europeans are not significant in any Lebanese group today-in particular, Lebanese Christians are today genetically similar to local people who lived during the Roman period which preceded the Crusades by more than four centuries.

Whole-genome resequencing provides insights into the population structure and domestication signatures of ducks in eastern China.

BACKGROUND: Duck is an ancient domesticated animal with high economic value, used for its meat, eggs, and feathers. However, the origin of indigenous Chinese ducks remains elusive. To address this question, we performed whole-genome resequencing to first explore the genetic relationship among variants of these domestic ducks with their potential wild ancestors in eastern China, as well as understand how the their genomes were shaped by different natural and artificial selective pressures. RESULTS: Here, we report the resequencing of 60 ducks from Chinese spot-billed ducks (Anas zonorhyncha), mallards (Anas platyrhnchos), Fenghua ducks, Shaoxing ducks, Shanma ducks and Cherry Valley Pekin ducks of eastern China (ten from each population) at an average effective sequencing depth of ~ 6× per individual. The results of population and demographic analysis revealed a deep phylogenetic split between wild (Chinese spot-billed ducks and mallards) and domestic ducks. By applying selective sweep analysis, we identified that several candidate genes, important pathways and GO categories associated with artificial selection were functionally related to cellular adhesion, type 2 diabetes, lipid metabolism, the cell cycle, liver cell proliferation, and muscle functioning in domestic ducks. CONCLUSION: Genetic structure analysis showed a close genetic relationship of Chinese spot-billed ducks and mallards, which supported that Chinese spot-billed ducks contributed to the breeding of domestic ducks. During the long history of artificial selection, domestic ducks have developed a complex biological adaptation to captivity.

Reconstructing cranial evolution in an extinct hominin.

Homo erectus is the first hominin species with a truly cosmopolitan distribution and resembles recent humans in its broad spatial distribution. The microevolutionary events associated with dispersal and local adaptation may have produced similar population structure in both species. Understanding the evolutionary population dynamics of H. erectus has larger implications for the emergence of later Homo lineages in the Middle Pleistocene. Quantitative genetics models provide a means of interrogating aspects of long-standing H. erectus population history narratives. For the current study, cranial fossils were sorted into six major palaeodemes from sites across Africa and Asia spanning 1.8-0.1 Ma. Three-dimensional shape data from the occipital and frontal bones were used to compare intraspecific variation and test evolutionary hypotheses. Results indicate that H. erectus had higher individual and group variation than Homo sapiens, probably reflecting different levels of genetic diversity and population history in these spatially disperse species. This study also revealed distinct evolutionary histories for frontal and occipital bone shape in H. erectus, with a larger role for natural selection in the former. One scenario consistent with these findings is climate-driven facial adaptation in H. erectus, which is reflected in the frontal bone through integration with the orbits.

Central American and Caribbean population history of the Pseudocercospora fijiensis fungus responsible for the latest worldwide pandemics on banana.

Among the emerging fungal diseases threatening food security, the Pseudocercospora fijiensis fungus causing black leaf streak disease of banana is one of the most marked examples of a recent worldwide pandemic on a major crop. We assessed how this pathogen spread throughout the latest invaded region, i.e. Central America and the Caribbean. We retraced its population history combining detailed monitoring information on disease outbreaks and population genetic analyses based on large-scale sampling of P. fijiensis isolates from 121 locations throughout the region. The results first suggested that sexual reproduction was not lost during the P. fijiensis expansion, even in the insular Caribbean context, and a high level of genotypic diversity was maintained in all the populations studied. The population genetic structure of P. fijiensis and historical data showed that two disease waves swept northward and southward in all banana-producing countries in the study area from an initial entry point in Honduras, probably mainly through gradual stepwise spore dispersal. Serial founder events accompanying the northern and southern waves led to the establishment of two different genetic groups. A different population structure was detected on the latest invaded islands (Martinique, Dominica and Guadeloupe), revealing multiple introductions and admixture events that may have been partly due to human activities. The results of this study highlight the need to step up surveillance to limit the spread of other known emerging diseases of banana spread mainly by humans, but also to curb gene flow between established pathogen populations which could increase their evolutionary potential.

Forensic features and genetic legacy of the Baloch population of Pakistan and the Hazara population across Durand line revealed by Y-chromosomal STRs.

The Hazara population across Durand line has experienced extensive interaction with Central Asian and East Asian populations. Hazara individuals have typical Mongolian facial appearances and they called themselves descendants of Genghis Khan's army. The people who speak the Balochi language are called Baloch. Previously, a worldwide analysis of Y-chromosomal haplotype diversity for rapidly mutating (RM) Y-STRs and with PowerPlex Y23 System (Promega Corporation Madison, USA) kit was created with collaborative efforts, but Baloch and Hazara population from Pakistan and Hazara population from Afghanistan were missing. In the current study, Yfiler Plus PCR Amplification Kit loci were examined in 260 unrelated Hazara individuals from Afghanistan, 153 Hazara individuals, and 111 Balochi individuals from Baluchistan Pakistan. For the Hazara population from Afghanistan and Pakistan overall, 380 different haplotypes were observed on these 27 Y-STR loci, gene diversities ranged from 0.51288 (DYS389I) to 0.9257 (DYF387S1), and haplotype diversity was 0.9992. For the Baloch population, every individual was unique at 27 Y-STR loci; gene diversity ranged from 0.5718 (DYS460) to 0.9371(DYF387S1). Twelve haplotypes were shared between 178 individuals, while only two haplotypes among these twelve were shared between 87 individuals in Hazara populations. Rst and Fst pairwise genetic distance analyses, multidimensional scaling plot, neighbor-joining tree, linear discriminatory analysis, and median-joining network were performed, which shed light on the history of Hazara and Baloch populations. The results of our study showed that the Yfiler Plus PCR Amplification Kit marker set provided substantially stronger discriminatory power in the Baloch population of Pakistan and the Hazara population across the Durand line.

An early Holocene human skull from Zhaoguo cave, Southwestern China.

OBJECTIVES: In this study, we describe a newly excavated early Holocene human cranium from Guizhou, Southwestern China, namely the Zhaoguo M1 (ZG 1). We aim to evaluate its morphological resemblance with Late Pleistocene human, and Northern and Southern China Neolithic populations. We also aim to infer its position in the process of East Asian population regionalization. MATERIALS AND METHODS: The ZG 1 skull is almost complete, only missing parts of the right parietal and the basicranium around the foramen magnum. Comparative samples include Late Pleistocene humans and Neolithic populations from Northern and Southern China. Univariate and multivariate analyses are carried out in the study. RESULTS: ZG 1 has a dolichocephalic cranium, wide zygomatic breadth, moderate glabella and supraobtial projection, marked canine fossa, and thin cranial vault. The nasal floor, maximum cranial breadth position, and frontal arc proportion are all congruent with modern human. Statistical analysis suggests that ZG 1's measurements are most similar to those of Southern China Neolithic specimens, with some closer to Late Pleistocene humans. CONCLUSION: ZG 1 shows a clear affinity with Southern China Neolithic populations, providing further support that regionalization of morphological variability patterns between Northern and Southern Neolithic populations could have originated at least 10,000 years ago.