Computational population genomics

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 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.

Since leaving Africa, human populations have gone through a series of range expansions. While the genomic signatures of these expansions are well detectable on a continental scale, the genomic consequences of small-scale expansions over shorter time spans are more challenging to disentangle. The medieval migration of the Walser people from their homeland in ssouthern Switzerland (Upper Valais) into other regions of the Alps is a good example of such a comparatively recent geographic and demographic expansion in humans. While several studies from the 1980s, based on allozyme markers, assessed levels of isolation and inbreeding in individual Walser communities, they mostly did so by focusing on a single community at a time. Here, we provide a comprehensive overview of genetic diversity and differentiation based on samples from multiple Walser, Walser-homeland, and non-Walser Alpine communities, along with an idealized (simulated) Swiss reference population (Ref-Pop). To explore genetic signals of the Walser migration in the genomes of their descendants, we use a set of forensic autosomal STRs as well as uniparental markers. Estimates of pairwise F based on autosomal STRs reveal that the Walser-homeland and Walser communities show low to moderate genetic differentiation from the non-Walser Alpine communities and the idealized Ref-Pop. The geographically more remote and likely more isolated Walser-homeland community of Lötschental and the Walser communities of Vals and Gressoney appear genetically more strongly differentiated than other communities. Analyses of mitochondrial DNA revealed the presence of haplogroup W6 among the Walser communities, a haplogroup that is otherwise rare in central Europe. Our study contributes to the understanding of genetic diversity in the Walser-homeland and Walser people, but also highlights the need for a more comprehensive study of the population genetic structure and evolutionary history of European Alpine populations using genome-wide data.

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.

In an effort to halt the global decline of large carnivores, reintroductions have become increasingly popular to establish satellite populations and reduce the risk of stochastic events. These artificial range expansions are typically formed by a small number of founders, which can lead to changes in population genetic structure. For instance, serial founder events can lead to neutral and even deleterious alleles reaching higher than expected frequencies along the front end of an expansion, referred to as gene surfing. One of the world’s most extensive range expansion programmes has been for endangered African wild dogs (Lycaon pictus). In this study, we examine the effect of continent-wide translocations on spatial genetic diversity, by determining what effect genetic surfing has on population structure in wild dogs, and measuring how long it will take for population structure to homogenize in the face of ongoing dispersal. We used a set of microsatellite loci to look at surfing alleles in five populations across southern Africa, and simulated the movement of these alleles forward in time under the current demographic scenario. We found that it would take about 150 generations for the expanding population to be 50% introgressed with genes from the free-roaming population. With the current rate of translocations, genetic differentiation in southern Africa will disappear, overturning the effects of genetic drift or surfing alleles. Understanding genetic patterns in expanding populations is of great interest to conservation, and we demonstrate that reintroduction programmes can help restore genetic diversity, and consequently adaptive potential, in recovering wildlife populations.

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remains 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 two-population system and described temporal neutral introgression patterns under a single- and two-pulse admixture model. We computed six 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 two statistics could confidently be used to infer inter-lineage 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 () started before the extinction of Neanderthals (). 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.

Preserving natural genetic diversity and ecological function of wild species is a central goal in conservation biology. As such, anthropogenic hybridization is considered a threat to wild populations, as it can lead to changes in the genetic makeup of wild species and even to the extinction of wild genomes. In European wildcats, the genetic and ecological impacts of gene flow from domestic cats are mostly unknown at the species scale. However, in small and isolated populations, it is known to include genetic swamping of wild genomes. In this context, it is crucial to better understand the dynamics of hybridization across the species range, to inform and implement management measures that maintain the genetic diversity and integrity of the European wildcat. In the present paper, we aim to provide an overview of the current scientific understanding of anthropogenic hybridization in European wildcats, to clarify important aspects regarding the evaluation of hybridization given the available methodologies, and to propose guidelines for management and research priorities.

The analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.

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.

In a recent article, Immel et al. (Immel A, Key FM, Szolek A, Barquera R, Robinson MK, Harrison GF, Palmer WH, Spyrou MA, Susat J, Krause-Kyora B, et al. 2021. Analysis of genomic DNA from medieval plague victims suggests long-term effect of Yersinia pestis on human immunity genes. Mol Biol Evol. 38:4059-4076) extracted DNA from 36 individuals dead from plague in Ellwangen, Southern Germany, during the 16th century. By comparing their human leukocyte antigen (HLA) genotypes with those of 50 present-day Ellwangen inhabitants, the authors reported a significant decrease of HLA-B*51:01 and HLA-C*06:02 and a significant increase of HLA-DRB1*13:01/13:02 frequencies from ancient to modern populations. After comparing these frequencies with a larger sample of 8,862 modern Germans and performing simulations of natural selection, they concluded that these changes had been driven by natural selection. In an attempt to provide more evidence on such stimulating results, we explored the HLA frequency patterns over all of Europe, we predicted binding affinities of HLA-B/C/DRB1 alleles to 106,515 Yersinia pestis-derived peptides, and we performed forward simulations of HLA genetic profiles under neutrality. Our analyses do not sustain the conclusions of HLA protection or susceptibility to plague based on ancient DNA.

The analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.

The Bronze Age is a complex period of social, cultural and economic changes. Recent paleogenomic studies have documented a large and rapid genetic change in early Bronze Age populations from Central Europe. However, the detailed demographic and genetic processes involved in this change are still debated. Here we have used spatially explicit simulations of genomic components to better characterize the demographic and migratory conditions that may have led to this change. We investigated various scenarios representing the expansion of pastoralists from the Pontic steppe, potentially linked to the Yamnaya cultural complex, and their interactions with local populations in Central Europe, considering various eco-evolutionary factors, such as population admixture, competition and long-distance dispersal. Our results do not support direct competition but rather the cohabitation of pastoralists and farmers in Central Europe, with limited gene flow between populations. They also suggest occasional long-distance migrations accompanying the expansion of pastoralists and a demographic decline in both populations following their initial contact. These results link recent archaeological and paleogenomic observations and move further the debate of genomic changes during the early Bronze Age.

The Covid-19 outbreak has triggered a global crisis that is challenging governments, health systems and the scientific community worldwide. A central question in the Covid-19 pandemic is whether climatic factors have influenced its progression. To address this question, we used mortality rates during the first three weeks of recorded mortality in 144 countries, during the first wave of the pandemic. We examined the effect of climatic variables, along with the proportion of the population older than 64 years old, the number of beds in hospitals, and the timing and strength of the governmental travel measures to control the spread of the disease. Our first model focuses on air temperature as the central climatic factor and explains 67% of the variation in mortality rate, with 37% explained by the fixed variables considered and 31% explained by country-specific variations. We show that mortality rate is negatively influenced by warmer air temperature. Each additional Celsius degree decreases mortality rate by ~5%. Our second model is centred on the UV Index and follows the same trend as air temperature, explaining 69% of the variation in mortality rate. These results are robust to the exclusion of countries with low incomes, as well as to the exclusion of low- and medium-income countries. We also show that the proportion of vulnerable age classes and access to healthcare are critical factors impacting the mortality rate of this disease. The effects of air temperature at an early stage of the Covid-19 outbreak is a key factor to understand the primary spread of this pandemic, and should be considered in projecting subsequent waves.

Humans are a highly mobile species that has colonized the entire globe in a few tens of thousands of years after it went out of Africa. There are still many unknowns about the routes followed by our ancestors during this expansion process, which has been influenced by various environmental, biological, and cultural factors, but these migrations have contributed to shape the genetic diversity of our species. A powerful approach to study the consequences of human dispersal on our genome is the modelling of complex evolutionary scenarios via computer simulation. In this chapter, we present three types of approaches used to simulate human dispersal in a geographic landscape. We focus on a spatially explicit method, simulating the demographic and migratory dynamic of populations forward in time and their resulting genetic diversity backward in time using the coalescent. We describe this approach and illustrate its interest with two important results: the process of gene surfing during population expansion and the genetic consequences of hybridization during species expansions. We show that a relatively simple scenario of global expansion of Homo sapiens from Africa, with rare hybridization events with archaic humans, such as Neanderthals or Denisovans, over a large geographic area reasonably explains the introgression pattern of archaic DNA in the genome of our species.

The accumulation of genome-wide molecular data has emphasized the important role of hybridization in the evolution of many organisms, which may carry introgressed genomic segments resulting from past admixture events with other taxa. Despite a number of examples of hybridization occurring during biological invasions, the resulting spatial patterns of genomic introgression remain poorly understood. Preliminary simulation studies have suggested a heterogeneous spatial level of introgression for invasive taxa after range expansion. We investigated in detail the robustness of this pattern and its persistence over time for both invasive and local organisms. Using spatially explicit simulations, we explored the spatial distribution of introgression across the area of colonization of an invasive taxon hybridizing with a local taxon. The general pattern for neutral loci supported by our results is an increasing introgression of local genes into the invasive taxon with the increase in the distance from the source of the invasion and a decreasing introgression of invasive genes into the local taxon. However, we also show there is some variation in this general trend depending on the scenario investigated. Spatial heterogeneity of introgression within a given taxon is thus an expected neutral pattern in structured populations after a biological invasion with a low to moderate amount of hybridization. We further show that this pattern is consistent with published empirical observations. Using additional simulations, we argue that the spatial pattern of Neanderthal introgression in modern humans, which has been documented to be higher in Asia than in Europe, can be explained by a model of hybridization with Neanderthals in Eurasia during the range expansion of modern humans from Africa. Our results support the view that weak hybridization during range expansion may explain spatially heterogeneous introgression patterns without the need to invoke selection.

Hybridization between wild and domesticated organisms is a worldwide conservation issue. In the Jura Mountains, threatened European wildcats () have been demographically spreading for approximately the last 50 years, but this recovery is coupled with hybridization with domestic cats (). Here, we project the pattern of future introgression using different spatially explicit scenarios to model the interactions between the two species, including competition and different population sizes. We project the fast introgression of domestic cat genes into the wildcat population under all scenarios if hybridization is not severely restricted. If the current hybridization rate and population sizes remain unchanged, we expect the loss of genetic distinctiveness between wild and domestic cats at neutral nuclear, mitochondrial and Y chromosome markers in one hundred years. However, scenarios involving a competitive advantage for wildcats and a future increase in the wildcat population size project a slower increase in introgression. We recommend that future studies assess the fitness of these hybrids and better characterize their ecological niche and their ecological interactions with parental species to elucidate effective conservation measures.

A dramatic increase in the hybridization between historically allopatric species has been induced by human activities. However, the notion of hybridization seems to lack consistency in two respects. On the one hand, it is inconsistent with the biological species concept, which does not allow for interbreeding between species, and on the other hand, it is considered either as an evolutionary process leading to the emergence of new biodiversity or as a cause of biodiversity loss, with conservation implications. In the first case, we argue that conservation biology should avoid the discussion around the species concept and delimit priorities of conservation units based on the impact on biodiversity if taxa are lost. In the second case, we show that this is not a paradox but an intrinsic property of hybridization, which should be considered in conservation programmes. We propose a novel view of conservation guidelines, in which human-induced hybridization may also be a tool to enhance the likelihood of adaptation to changing environmental conditions or to increase the genetic diversity of taxa affected by inbreeding depression. The conservation guidelines presented here represent a guide for the development of programmes aimed at protecting biodiversity as a dynamic evolutionary system.

Cavalli-Sforza and coauthors originally explored the genetic variation of modern humans throughout the world and observed an overall east-west genetic gradient in Asia. However, the specific environmental and population genetics processes causing this gradient were not formally investigated and promoted discussion in recent studies. Here we studied the influence of diverse environmental and population genetics processes on Asian genetic gradients and identified which could have produced the observed gradient. To do so, we performed extensive spatially-explicit computer simulations of genetic data under the following scenarios: (i) variable levels of admixture between Paleolithic and Neolithic populations, (ii) migration through long-distance dispersal (LDD), (iii) Paleolithic range contraction induced by the last glacial maximum (LGM) and, (iv) Neolithic range expansions from one or two geographic origins (the Fertile Crescent and the Yangzi and Yellow River Basins). Next, we estimated genetic gradients from the simulated data and we found that they were sensible to the analyzed processes, especially to the range contraction induced by LGM and to the number of Neolithic expansions. Some scenarios were compatible with the observed east-west genetic gradient, such as the Paleolithic expansion with a range contraction induced by the LGM or two Neolithic range expansions from both the east and the west. In general, LDD increased the variance of genetic gradients among simulations. We interpreted the obtained gradients as a consequence of both allele surfing caused by range expansions and isolation by distance along the vast east-west geographic axis of this continent.

SPLATCHE3 simulates genetic data under a variety of spatially explicit evolutionary scenarios, extending previous versions of the framework. The new capabilities include long-distance migration, spatially and temporally heterogeneous short-scale migrations, alternative hybridization models, simulation of serial samples of genetic data and a large variety of DNA mutation models. These implementations have been applied independently to various studies, but grouped together in the current version.