Biology subjects

Excoffier, L.

Publications and source records attributed to Excoffier, L..

15 recordsLinked to original sources

bioRxiv2025

Evolution of functional genomic diversity during a bottleneck

Most species have been through population bottlenecks and range expansions, and the impact of these events on patterns of diversity has been well studied. In particular, it has been shown that initially rare neutral variants could readily fix on the front of range expansions or during bottlenecks, giving genomic signatures looking like selective sweeps. Here we expand on previous work by considering the dynamics of genomic diversity in (functional) regions harbouring deleterious variants during bottlenecks or during range expansions modelled as serial founder effects. We find that regions with very low levels of diversity (troughs) looking like selective sweeps can also readily form in these functional regions. Additionally, their properties depend on the dominance level of deleterious mutations. Trough density is higher and increases more rapidly in regions with co-dominant deleterious mutations than in regions with recessive mutations. Interestingly, we find that genetic diversity declines less rapidly in regions with partially recessive mutations than in regions with codominant ones or in regions with only neutral mutations. These features are generally enhanced in low recombination regions and for intermediate selection coefficients. If most deleterious mutations in a genome are partially recessive, it follows that functional low recombination regions should better preserve genetic diversity during range expansions than neutral regions of the genome. Significance statementMost research on the effects of selection on genetic diversity have been done in equilibrium populations, leaving a gap in our understanding of how selection acting on functional regions interacts with demographic changes. Our study reveals strikingly different impacts of purifying selection on genetic diversity depending on the dominance coefficient of deleterious mutations. While codominant variants create diversity dips resembling selective sweeps, recessive mutations can preserve genetic diversity during bottlenecks through the relatively understudied phenomenon of pseudo-overdominance. Our findings show how selective and demographic forces interact in more complex ways than previously thought and emphasize the importance of further exploring these dynamics to accurately interpret genetic variation in natural populations.

genetics↗

bioRxiv2024

A generalized structured coalescent for purifying selection without recombination

Purifying selection is a critical factor in shaping genetic diversity. Current theoretical models only address scenarios of either very weak or strong selection, leaving a significant gap in our knowledge. The effects of purifying selection on patterns of genomic diversity remain poorly understood when selection against deleterious mutations is weak to moderate, particularly when recombination is limited or absent. In this study, we extend an existing approach, the fitness-class coalescent, to incorporate arbitrary levels of purifying selection. This model offers a comprehensive framework for exploring the influence of purifying selection in a wide range of demographic scenarios. Moreover, our research reveals potential sources of qualitative and quantitative biases in demographic inference, highlighting the significant risk of attributing genetic patterns to past demographic events rather than purifying selection. This work expands our understanding of the complex interplay between selection, drift, and population dynamics, and how purifying selection distorts demographic inference.

genetics↗

bioRxiv2021

Statistical inference in population genomics

The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population-genetic insights out-paced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes. For example, the approach of directly investigating models of adaptive evolution in each newly sequenced population or species often neglects the fact that a thorough characterization of ubiquitous non-adaptive processes is a prerequisite for accurate inference. We here describe the perils of these tendencies, present our consensus views on current best practices in population genomic data analysis, and highlight areas of statistical inference and theory that are in need of further attention. Thereby, we argue for the importance of defining a biologically relevant baseline model tuned to the details of each new analysis, of skepticism and scrutiny in interpreting model-fitting results, and of carefully defining addressable hypotheses and underlying uncertainties.

evolutionary biology↗

bioRxiv2021

Strong neutral sweeps occurring during a population contraction

A strong reduction in diversity around a specific locus is often interpreted as a recent rapid fixation of a positively selected allele, a phenomenon called a selective sweep. Rapid fixation of neutral variants can however lead to similar reduction in local diversity, especially when the population experiences changes in population size, e.g., bottlenecks or range expansions. The fact that demographic processes can lead to signals of nucleotide diversity very similar to signals of selective sweeps is at the core of an ongoing discussion about the roles of demography and natural selection in shaping patterns of neutral variation. Here we quantitatively investigate the shape of such neutral valleys of diversity under a simple model of a single population size change, and we compare it to signals of a selective sweep. We analytically describe the expected shape of such "neutral sweeps" and show that selective sweep valleys of diversity are, for the same fixation time, wider than neutral valleys. On the other hand, it is always possible to parametrize our model to find a neutral valley that has the same width as a given selected valley. We apply our framework to the case of a putative selective sweep signal around the gene Quetzalcoatl in D. melanogaster and show that the valley of diversity in the vicinity of this gene is compatible with a short bottleneck scenario without selection. Our findings provide further insight in how simple demographic models can create valleys of genetic diversity that may falsely be attributed to positive selection.

evolutionary biology↗

bioRxiv2020

The mixed genetic origin of the first farmers of Europe

The precise genetic origins of the first Neolithic farming populations, as well as the processes and the timing of their differentiation, remain largely unknown. Based on demogenomic modeling of high-quality ancient genomes, we show that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Near Eastern population with a strongly bottlenecked Western hunter-gatherer population after the Last Glacial Maximum. Moreover, the population branch leading to the first farmers of Europe and Anatolia is characterized by a 2,500-year period of extreme genetic drift during its westward range expansion. Based on these findings, we derive a spatially explicit model of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene. One-Sentence SummaryEarly European farmers emerged from multiple post LGM mixtures and experienced extreme drift during their westward expansion.

evolutionary biology↗

bioRxiv2020

Runs of homozygosity in killer whale genomes provide a global record of demographic histories

Runs of homozygosity (ROH) occur when offspring receive the same ancestral haplotype from both parents, and, accordingly, reduce individual heterozygosity. Their distribution throughout the genome contains information on the probability of inbreeding mediated by mating system and population demography. Here, we investigate variation in killer whale demographic history as reflected in genome-wide heterozygosity, using a global dataset of 26 genomes. We find an overall pattern of lower heterozygosity in genomes sampled at high latitudes, with hundreds of short ROH (< 1Mbp) reflecting high background relatedness due to coalescence of haplotypes during bottlenecks associated with founder events during post-glacial range expansions. Across most of the species range, intermediate length ROH (1-10Mb) revealed long-term inbreeding in 22 of the 26 sampled killer whale genomes, consistent with the high social philopatry observed in all populations studied to date. Inbreeding coefficients (FROH) were comparable to those reported in other taxa with long-term low population size, such as bonobos and the Native American Karitiana of the Brazilian Amazon. The extreme outlier in this dataset, a Scottish killer whale, was homozygous over one-third of the autosomes (41.6%) with a distinct distribution of ROH length, indicating generations of inbreeding. This exceeds autozygosity in emblematic examples of long-term inbreeding, such as the Altai Neanderthal, and eastern lowland and mountain gorillas. The fate of this Scottish killer whale population, in which no calves have been born in over two decades, may be inextricably linked to its demographic history and consequential inbreeding depression.

evolutionary biology↗

bioRxiv2019

Reconstruction of nine thousand years of agriculture-based diet and impact on human genetic diversity in Asia

Domestication of crops and animals during the Holocene epoch played a critical role in shaping human culture, diet and genetic variation. This domestication process took place across a span of time and space, especially in Asia. We hypothesize that domestication of plants and animals around the world must have influenced the human genome differentially among human populations to a far greater degree than has been appreciated previously. The range of domesticated foods that were available in different regions can be expected to have created regionally distinct nutrient intake profiles and deficiencies. To capture this complexity, we used archaeobotanical evidence to construct two models of dietary nutrient composition over a 9000 year time span in Asia: one based on Larson et al. (2014) and measured through composition of 8 nutrients, and another taking into account a wider range of crops, cooking and lifestyle variation, and the dietary variables glycemic index and carbohydrate content. We hypothesize that the subtle dietary shifts through time and space have also influenced current human genetic variation among Asians. We used statistical methods BayeScEnv, BayeScan and Baypass, to examine the impact of our reconstructed long-term dietary habits on genome-wide genetic variation in 29 current-day Asian populations (Figure S1, Figure 1, Figure 2). Our results show that genetic variation in diet-related pathways is correlated with dietary differences among Asian populations. SNPs in five genes, GHR, LAMA1, SEMA3A, CAST and TCF7L2, involved in the gene ontologies salivary gland morphogenesis and negative regulation of type B pancreatic cell apoptotic process suggest that metabolism may have been primary targets of selection driven by dietary shifts. These shifts may have influenced biological pathways in ways that have a lasting impact on health. We present a case that archaeobotanical evidence can provide valuable insight for understanding how historical human niche construction might have influenced modern human genetic variation.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC=\"FIGDIR/small/747709v1_fig1.gif\" ALT=\"Figure 1\">\nView larger version (26K):\norg.highwire.dtl.DTLVardef@1aa917corg.highwire.dtl.DTLVardef@135990forg.highwire.dtl.DTLVardef@1d3e0d3org.highwire.dtl.DTLVardef@14d5112_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Organization of the study and analysis pipeline. The two figures in column Archaeological data refer to the two constructed dietary models, with the boxes beside them referring to the dietary variables from each model.\n\nC_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC=\"FIGDIR/small/747709v1_fig2a.gif\" ALT=\"Figure 2\">\nO_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC=\"FIGDIR/small/747709v1_fig2b.gif\" ALT=\"Figure 2\">\nView larger version (52K):\norg.highwire.dtl.DTLVardef@1059950org.highwire.dtl.DTLVardef@94662dorg.highwire.dtl.DTLVardef@c01de2org.highwire.dtl.DTLVardef@ea07cb_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO Summary of Diet Model 1. a) Levels of nutrients contributed by domestication, based on Diet Model 1, as a sum total of values across all three population groups. b) Average levels of nutrients across the three time intervals (9000 YBP-present) in each region, based on Diet Model 1. Supplementary Tables 1-8 contain the data used to generate these figures.\n\nC_FIG

genetics↗

bioRxiv2019

Transition from background selection to associative overdominance promotes diversity in regions of low recombination

Linked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

evolutionary biology↗

bioRxiv2019

Polygenic patterns of adaptive introgression in modern humans are mainly shaped by response to pathogens

Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (sub-networks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity-related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.

evolutionary biology↗

bioRxiv2019

Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection

Formulating strategies for species conservation requires knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, the evolutionary history and genomic variation of tigers remain poorly known. With 70% of the worlds wild tigers living in India, such knowledge is critical for tiger conservation. We re-sequenced 65 individual tiger genomes across their extant geographic range, representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding, possibly because of small and fragmented protected areas. Surprisingly, demographic models suggest recent divergence (within the last 10,000 years) between populations, and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection mainly related to metabolic adaptation to cold, while Sumatran tigers show evidence of evolving under weak selection for genes involved in body size regulation. Depending on conservation objectives, our results support the isolation of Amur and Sumatran tigers, while geneflow between Malayan and South Asian tigers may be considered. Further, the impacts of ongoing connectivity loss on the health and persistence of tigers in India should be closely monitored.

genomics↗

bioRxiv2018

Genomic analysis of fast expanding bacteria reveals new molecular adaptive mechanisms

Bacterial populations have been shown to accumulate deleterious mutations during spatial expansions that overall decrease their fitness and ability to grow. However, it is unclear if and how they can respond to selection in face of this mutation load. We examine here if artificial selection can counteract the negative effects of range expansions. We investigated the molecular evolution of 20 lines (SEL) selected for fast expansions and compared them to 20 lines without artificial selection (CONTROL). We find that all 20 SEL lines have been able to increase their expansion speed relative to the ancestral line, unlike CONTROL lines, showing that enough beneficial mutations are produced during spatial expansions to counteract the negative effect of expansion load. Importantly, SEL and CONTROL lines have similar numbers of mutations indicating that they evolved for the same number of generations and that increased fitness is not due to a purging of deleterious mutations. We find that loss of function (LOF) mutations are better at explaining the increased expansion speed of SEL lines than non-synonymous mutations or a combination of the two. Interestingly, most LOF mutations are found in simple sequence repeats located in genes involved in gene regulation and gene expression. We postulate that such potentially reversible mutations could play a major role in the rapid adaptation of bacteria to changing environmental conditions by shutting down expensive genes and adjusting gene expression.\n\nAuthor SummaryWe investigated if strong artificial selection for fast expansion can counteract the negative effects of range expansion which had been shown to lead to an accumulation of deleterious mutations. This experiments showed that i) an increase in expansion speed could occur if bacteria were selected from the largest protruding sectors, and ii) that artificially selected bacterial lines accumulated about the same number of mutations than simply expanding line suggesting that the observed increased fitness is not due to increased purifying selection where deleterious mutations would have been removed in fast growing lines. We find that loss of function (LOF) mutations are best explaining the observed increased expansion speed in selected lines. These mutations, which are known to play an important role in adaptive processes in bacterial populations, frequently consist in small insertion-deletions in simple sequence repeats, and are thus relatively easily reversible. They could thus act as switches that can reversibly shut down genes. Our results therefore suggest that shutting down expensive genes and adjusting gene expression are important for adaptive processes during range expansion.

evolutionary biology↗

bioRxiv2018

Mutation load dynamics during environmentally-driven range shifts

The fitness of spatially expanding species has been shown to decrease over time and space, but specialist species tracking their changing environment and shifting their range accordingly have been little studied. We use individual-based simulations and analytical modeling to compare the impact of range expansions and range shifts on genetic diversity and fitness loss, as well as the ability to recover fitness after either a shift or expansion. We find that the speed of a shift has a strong impact on fitness evolution. Fastest shifts show the strongest fitness loss per generation, but intermediate shift speeds lead to the strongest fitness loss per geographic distance. Range shifting species lose fitness more slowly through time than expanding species, however, their fitness compared at equivalent geographic distances spread can be considerably lower. These counter-intuitive results arise from the combination of time over which selection acts and mutations enter the system. Range shifts also exhibit reduced fitness recovery after a geographic shift and may result in extinction, whereas range expansions can persist from the core of the species range. The complexity of range expansions and range shifts highlights the potential for severe consequences of environmental change on species survival.\n\nAuthor SummaryAs environments change through time across the globe, species must adapt or relocate to survive. Specialized species must track the specific moving environments to which they are adapted, as compared to generalists which can spread widely. During colonization of new habitat, individuals can accumulate deleterious alleles through repeated bottlenecks. We show through simulation and analytic modeling that the process by which these alleles accumulate changes depending upon the speed at which populations spread over a landscape. This is due to the increased efficacy of selection against deleterious variants at slow speeds of range shifts and decreased input of mutations at faster speeds of range shifts. Under some selective circumstances, shifting of a species range leads to extinction of the entire population. This suggests that the rate of environmental change across the globe will play a large role in the survival of specialist species as compared to more generalist species.

evolutionary biology↗

bioRxiv2017

The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow

The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island-specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 660,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, mutations at this locus are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration.

evolutionary biology↗

bioRxiv2017

Detecting Gene Subnetworks Under Selection In Biological Pathways

Advances in high throughput sequencing technologies have created a gap between data production and functional data analysis. Indeed, phenotypes result from interactions between numerous genes, but traditional methods treat loci independently, missing important knowledge brought by network-level emerging properties. Therefore, evidencing selection acting on multiple genes affecting the evolution of complex traits remains challenging. In this context, gene network analysis provides a powerful framework to study the evolution of adaptive traits and facilitates the interpretation of genome-wide data. To tackle this problem, we developed a method to analyse gene networks that is suitable to evidence polygenic selection. The general idea is to search biological pathways for subnetworks of genes that directly interact with each other and that present unusual evolutionary features. Subnetwork search is a typical combinatorial optimization problem that we solve using a simulated annealing approach. We have applied our methodology to find signals of adaptation to high-altitude in human populations. We show that this adaptation has a clear polygenic basis and is influenced by many genetic components. Our approach improves on classical tests for selection based on single genes by identifying both new candidate genes and new biological processes involved in adaptation to altitude.

bioinformatics↗

bioRxiv2016

Accumulation of deleterious mutations during bacterial range expansions

Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present 3-4 times fewer mutations. Estimation of the distribution of fitness effect (DFE) under a spatially explicit model reveals a mean negative effect for new mutations (-0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, we show that the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines remained unchanged. Our results thus suggest that successful expanding species are affected by deleterious mutations that accumulate during the expansion process, leading to a drastic impairment of their evolutionary potential.

evolutionary biology↗