Mathias Currat

During their expansion from Africa, modern humans interbred with Neanderthals, resulting in introgression of Neanderthal DNA into their genomes. This process contributed to a Southeast-to-Northwest gradient of Neanderthal ancestry across Europe. We investigate the population dynamics underlying the emergence and persistence of this gradient through two successive human range expansions. We developed a three-population, layered, spatially explicit simulation framework to track the spatiotemporal evolution of Neanderthal ancestry under a model of interactions among Neanderthals, pre-Neolithic hunter-gatherers, and Neolithic farmers. Our results indicate that the ancestry cline emerged from the interplay between the direction of the initial hunter-gatherer expansion, the northern limit of the Neanderthal range, and strong reproductive isolation, without requiring natural selection. The similar direction of the subsequent Neolithic expansion explains the cline’s persistence and Neanderthal ancestry differences between hunter-gatherers and farmers. These findings demonstrate how spatiotemporal patterns in ancient DNA provide insights into past population dynamics.

During their expansion out of Africa, modern humans interbred with Neanderthals, leading to the introgression of Neanderthal DNA into their genomes. This initial dispersal created, in Europe, a Southeast–to–Northwest gradient of Neanderthal ancestry in European populations, which was preserved through later Neolithic migration. Here, we investigate the population dynamics that created and maintained this gradient across two successive expansions. We developed a three-population layered simulation framework to track the spatiotemporal evolution of Neanderthal ancestry under a model of interactions between Neanderthals, Palaeolithic hunter-gatherers, and Neolithic farmers. Our results indicate that the Neanderthal ancestry cline was shaped by the direction of the early hunter-gatherer expansion, the northern limit of the Neanderthal range, and strong reproductive isolation between lineages. We estimated that admixture between hunter-gatherers and Neolithic populations was an order of magnitude higher than that between Neanderthals and modern humans. These findings demonstrate how spatiotemporal analyses of ancient DNA provide insights into the dynamics and interactions of ancestral populations.

Interbreeding between closely related lineages is a pervasive evolutionary feature across taxa ¹ , including modern humans, who admixed with Neanderthals and other archaic hominins ^2,3 . Identifying where gene flow between these lineages happened can shed light on ecological and adaptive contexts in which introgressed genes were acquired. However, mapping ancient hybrid zones is challenging because post-admixture population dynamics obscure their genetic signatures. Here, we determine the conditions under which spatial patterns of introgressed DNA in ancient genomes allow the inference of the geographic location of past hybridization events during population expansions. Using computational simulations, we identify the conditions under which introgression-based statistics provide informative signals about past hybridization events. We show that the mean genomic proportion of introgressed DNA, which can be readily calculated from low-coverage ancient genomes, reveals a cline that increases with distance from the population expansion source until reaching the hybrid zone boundary and persists over time. Comparison with empirical Neanderthal introgression distribution from an extended Eurasian paleogenomic dataset supports a prolonged admixture pulse extending far beyond the Levant in western Eurasia. Our findings highlight the power of paleogenomics to reconstruct the spatiotemporal dynamics of species interactions.

The replacement of hunter-gatherer lifestyles by agriculture represents a pivotal change in human history. The initial stage of this Neolithic transition in Europe was instigated by the migration of farmers from Anatolia and the Aegean basin. In this study, we modeled the expansion of Neolithic farmers into central Europe along the continental route of dispersal. We used spatially explicit simulations of paleogenomic diversity and high-quality paleogenomic data from 67 prehistoric individuals to assess how population dynamics between Indigenous European hunter-gatherers and incoming farmers varied across space and time. Our results demonstrate that admixture between the two groups increased locally over time at each stage of the Neolithic expansion along the continental route. We estimate that the effective population size of farmers was about five times that of hunter-gatherers. In addition, we infer that sporadic long-distance migrations of early farmers contributed to their rapid dispersal, while competitive interactions with hunter-gatherers were limited.

The replacement of hunter-gatherer lifestyles by agriculture represents a pivotal change in human history. The initial stage of this Neolithic transition in Europe was instigated by the migration of farmers from Anatolia and the Aegean basin. In this study, we modeled the expansion of Neolithic farmers into Central Europe from Anatolia, along the Continental route of dispersal. We employed spatially explicit simulations of palaeogenomic diversity and high-quality palaeogenomic data from 67 prehistoric individuals to assess how population dynamics between indigenous European hunter-gatherers and incoming farmers varied across space and time. Our results demonstrate that admixture between the two groups increased locally over time at each stage of the Neolithic expansion along the Continental route. We estimate that the effective population size of farmers was about five times that of the hunter-gatherers. Additionally, we infer that sporadic long distance migrations of early farmers contributed to their rapid dispersal, while competitive interactions with hunter-gatherers were limited. Teaser The first farmers of continental Europe increasingly admixed over time with indigenous hunter-gatherers.

Testing the association between objects is central in ecology, evolution, and quantitative sciences in general. Two types of variables can describe the relationships between objects: point variables (measured on individual objects), and distance variables (measured between pairs of objects). The Mantel test and derived methods have been extensively used for distance variables. Yet, these methods have been criticized due to low statistical power and inflated type I error when spatial autocorrelation is present. Here, we assessed the statistical power between different types of tested variables and the type I error rate over a wider range of autocorrelation intensities than previously assessed, both on univariate and multivariate data. We also illustrated the performance of distance matrix statistics through computational simulations of genetic diversity. We show that the Mantel test and derived methods are not affected by inflated type I error when spatial autocorrelation affects only one variable when investigating correlations, or when either the response or the explanatory variable(s) is affected by spatial autocorrelation while investigating causal relationships. As previously noted, with autocorrelation affecting more variables, inflated type I error could be reduced by modifying the significance threshold. Additionally, the Mantel test has no problem of statistical power when the hypothesis is formulated in terms of distance variables. We highlight that transformation of variable types should be avoided because of the potential information loss and modification of the tested hypothesis. We propose a set of guidelines to help choose the appropriate method according to the type of variables and defined hypothesis.

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remain a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a 2-population system and described temporal neutral introgression patterns under a single- and 2-pulse admixture model. We computed 6 summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within genomes, as well as genome-wide introgression proportions and related measures. The first 2 statistics could confidently be used to infer interlineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.

The worldwide expansion of modern humans ( Homo sapiens ) started before the extinction of Neanderthals ( Homo neanderthalensis ). Both species coexisted and interbred, leading to slightly higher introgression in East Asians than in Europeans. This distinct ancestry level has been argued to result from selection, but range expansions of modern humans could provide an alternative explanation. This hypothesis would lead to spatial introgression gradients, increasing with distance from the expansion source. We investigate the presence of Neanderthal introgression gradients after past human expansions by analyzing Eurasian paleogenomes. We show that the out-of-Africa expansion resulted in spatial gradients of Neanderthal ancestry that persisted through time. While keeping the same gradient orientation, the expansion of early Neolithic farmers contributed decisively to reducing the Neanderthal introgression in European populations compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Paleolithic hunter-gatherers. This study shows that inferences about past human population dynamics can be made from the spatiotemporal variation in archaic introgression.

Summary: The worldwide expansion of modern humans ( Homo sapiens ) from Africa started before the extinction of Neanderthals ( Homo neanderthalensis ). Both species coexisted and interbred, as revealed by the sequencing of Neanderthal genomes, leading to ~2% Neanderthal DNA in modern Eurasians ^1,2 , with slightly higher introgression in East Asians than in Europeans ^3–6 . These distinct levels of ancestry have been argued to result from selection processes ^7,8 . However, recent theoretical simulations have shown that range expansions could be another explanation ^9,10 . This hypothesis would lead to the generation of spatial gradients of introgression, increasing with the distance from the source of the expansion, i.e., Africa for modern humans. Here, we investigate the presence of Neanderthal introgression gradients after past human expansions by analysing an extended palaeogenomic dataset of Eurasian populations. Our results show that the Out-of-Africa expansion of modern humans into Eurasia resulted in spatial gradients of Neanderthal ancestry that persisted through time. Moreover, while keeping the same gradient orientation, the expansion of early Neolithic farmers into western Eurasia contributed decisively to reducing the average level of Neandertal genomic introgression in European compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Palaeolithic hunter-gatherers. This study shows that inferences about past population dynamics within our species can be made from the spatiotemporal variation in archaic introgression.

The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.