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Laurent, R.

Publications and source records attributed to Laurent, R..

9 recordsLinked to original sources

The genetic legacy of archaic hominins in Central and Southeast Asia uncovers three distinct Denisovan populations

The sequencing of Neanderthal and Denisovan genomes has provided new insights into human evolution. Today, interactions between Neanderthals, Denisovans, and populations of European, East Asian, and Oceanian descent are well documented. However, neighboring regions such as Central and Southeast Asia remain understudied for archaic admixture despite their key geographic location and complex migration histories. To fill this gap, we investigate archaic ancestry in 16 populations from Central Asia and 14 from mainland Southeast Asia. Our results show that Neanderthal and Denisovan ancestry in these populations is of the same order of magnitude as in other Eurasian populations. However, although Denisovan ancestry accounts for less than 1% in mainland Asian populations, it originates from several admixture events involving different Denisovan populations. In particular, we find in Southeast Asia that Denisovan ancestry results from three distinct admixture events with three different Denisovan populations, highlighting the complexity of Denisovan contact with the ancestors of present-day Southeast Asian populations and providing new insights into the extensive geographic distribution of Denisovan populations.

evolutionary biology↗

Genomic insights into adaptation to eco-regional and cultural variables across human populations from North, Central and Southeast Asia

Natural selection has been extensively studied in humans, providing many examples of how climate, diet, and pathogens can translate into local selective pressures and thus phenotypic diversity across populations. However, most studies have focused either on a global scale, with a limited number of populations per geographic area, or on a very local scale. To complement these approaches, we collected and studied a large genomic dataset at a continental scale covering North, Central, and mainland Southeast Asia, and consisting of 863 individuals from 25 culturally diverse populations. We aimed to decipher the selective pressures across the Asian continent, comparing populations from different geographic areas and having contrasted subsistence strategies, using both intra-populations (iHS) and inter-populations (Fst) statistics. We detected both local and continental-wide signals, with some geographically and culturally complex patterns emerging when being compared to the literature. Interestingly, among the regions detected as significant only in mainland Southeast Asia, we found two of them clearly pointing to selective pressures associated with immunity. The first one, detected with iHS only, contains three peptidoglycan binding genes (REG1A, REG1B and REG3A) interacting with bacterial cell walls. The second region, the most significant one when intersecting iHS and Fst, contains PELI1, previously shown to modulate the immune and inflammatory response and to be under selection in Han Chinese and Oceanians. In addition, in North and Central Asia, we uncovered a region overlapping with PTPRC, a gene associated with viruses recognition, as well as another region including GPHB5, associated with lipid and carbohydrate metabolism. Interestingly, we further identified a signal on PTPRG, where variants have previously been associated with alcohol flushing in East Asia, not only in farmers but also in herders and hunter-gatherers, challenging the hypothesis that this phenotype was selected for in response to the transition to agriculture. In turn, when focusing on signals specific to given subsistence strategies, we found two genes related to immune functions (TUBA1B and HERC1 ) exclusively in herders. In conclusion, while many signals of selection likely remain to be uncovered in less studied human groups, deciphering whether they are linked to immune, dietary or climatic factors is challenging, as subsistence strategies often covary with climate, which further influence pathogenic loads.

genomics↗

Nested admixture during and after the Trans-Atlantic Slave Trade on the island of Sao Tome

Human admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of Sao Tome, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.5 million SNPs newly genotyped in 96 Sao Tomeans and found that geography alone cannot explain the observed patterns of genetic differentiation within the island. We defined five genetic groups in Sao Tome based on the hypothesis that individuals sharing the most haplotypes are more likely to share similar genetic histories. Using Identical-by-Descent and different local ancestry inference methods, we inferred shared ancestries between 70 African and European populations and each Sao Tomean genetic group. We identified admixture events between admixed groups that were previously isolated on the island, showing how recently admixed populations can be themselves the sources of other admixture events. This study demonstrates how complex admixture and isolation histories during and after the Transatlantic Slave-Trade shaped extant individual genetic patterns at a local scale in Africa.

genetics↗

Ancient tree-topologies and gene-flow processes among human lineages in Africa

The deep history of human evolution in Africa remains intensely debated, with increasingly complex models being proposed. To investigate this, we sequenced and analysed 73 novel high-quality whole genomes from 14 Central and Southern African populations with diverse cultural practices. Using extensive simulations and machine-learning Approximate Bayesian Computation (ABC), we jointly reconstructed their demographic history of divergences and migrations. We find extensive genome-wide diversity within and among populations, including substantial local genetic differentiation not fully explained by geography or cultural practices. These patterns highlight the importance of explicitly considering local genomic diversity when reconstructing human evolutionary history. We find that tree-like population histories with long periods of drift separated by short pulses of unidirectional gene-flow better explain the data than continuous gene-flow. Without invoking archaic admixture, our models accurately fit observed genomic variation and identify multiple episodes of gene-flow coinciding with major ecological and cultural changes in Sub-Saharan Africa.

genetics↗

Deep genetic substructure within bonobos

Establishing the genetic and geographic structure of populations is fundamental both to understand their evolutionary past and preserve their future, especially for endangered species. Nevertheless, the patterns of genetic population structure are unknown for most endangered species, including some of our closest living relatives. This is the case of bonobos (Pan paniscus) which together with chimpanzees (Pan troglodytes) are humans closest living relatives. Chimpanzees live across equatorial Africa and are classified into four subspecies (Groves, 2001), with some genetic population substructure even within subspecies. Conversely, bonobos live exclusively in the Democratic Republic of Congo and are considered a homogeneous group with low genetic diversity (Fischer et al. 2011) despite some population structure inferred from mtDNA. Nevertheless, mtDNA aside, their genetic structure remains unknown, hampering our understanding of the species and conservation efforts. Placing bonobos genetics in space is however challenging because, being endangered, only non-invasive sampling is possible for wild individuals. Here, we jointly analyse the exomes and mtDNA from 20 wild-born bonobos, the whole-genomes of 10 captive bonobos and the mtDNA of 61 wild individuals. We identify three genetically distinct bonobo groups of inferred Central, Western and Far-Western geographic origin within the bonobo range. We estimate the split time between the central and western populations to [~]145,000 years ago, and genetic differentiation to be in the order of that of the closest chimpanzee subspecies. We identify putative signatures of differential genetic adaptation among populations for genes associated with homeostasis, metabolism and the nervous system. Furthermore, our estimated long-term Ne for Far-West ([~]3,000) is among the lowest estimated for any great ape lineage. Our results highlight the need of attention to bonobo substructure, both in terms of research and conservation. Highlights- We identified three genetically distinct populations of bonobos, inferred as having Central, Western and Far-Western geographic origin within the species range. The estimated split time is [~]145,000 years ago for the Central and Western populations, and [~]60,000 years ago for the two Western populations. - The genetic differentiation between the Central and Far-Western bonobo populations is in the order of that between Central and Eastern chimpanzee subspecies, while the genetic differentiation among Western bonobo populations is similar to that among human groups. - Once substructure is accounted for, we infer a long-term effective population size (Ne) of only [~]3,000 for Far-Western bonobos, genetic isolation and inbreeding.

evolutionary biology↗

Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants

The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. The reason why viral evolution favors loss or inactivation of ORF8 is not fully understood, although the effects of ORF8 on inflammation, immune evasion, and disease severity have been described. Here we show -using clinical ORF8-deficient viral isolates, virus-like particles (VLPs) and viral replicons- that ORF8 expression dampens viral particle production. ORF8 physically interacts with the viral Spike protein and induces Golgi fragmentation, overall contributing to less virus particle production. Using systematic ORF8 deletions, we mapped the particle-reducing function to its N-terminal signal peptide. Interestingly, this part of ORF8 is severely truncated in the recent XBB.1.5 variant, and when restored, suppresses viral particle production in the context of the entire viral genome. Collectively, our data supports the model that evolutionary pressure exists to delete ORF8 sequence and expression across SARS-CoV-2 variants to fully enable viral particle production. ImportanceSARS-CoV-2 variants continue to emerge worldwide with advantages in replication and immune evasion. Many variants have acquired distinct mutations in independent lineages to abolish ORF8 expression. To understand the molecular mechanisms behind this evolutionary trend, we utilized reverse genetics, molecular virology, and confocal microscopy to show that ORF8 has antiviral functions by dampening viral particle production and inducing Golgi stress during infection. Our data demonstrate that SARS-CoV-2 is continuing its adaptation to optimize viral particle production and other unknown aspects of viral infection.

microbiology↗

The admixture histories of Cabo Verde

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants genomic diversity and structure on both sides of the Atlantic.

genetics↗

Detection of sexually antagonistic transmission distortions in trio datasets

Sex dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sex dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex-antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome-scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic selection. We rely on trio datasets where sex-biased transmission distortions can be directly tracked from parents to offspring, and allows identifying signal of sexually antagonistic transmission distortions in genomic regions. We report the genomic location and recombination pattern surrounding 66 regions detected as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidates regions for sexually antagonistic selection in humans.

evolutionary biology↗

Complex genetic admixture histories reconstructed with Approximate Bayesian Computations

Admixture is a fundamental evolutionary process that has influenced genetic patterns in numerous species. Maximum-likelihood approaches based on allele frequencies and linkage-disequilibrium have been extensively used to infer admixture processes from dense genome-wide datasets mostly in human populations. Nevertheless, complex admixture histories, beyond one or two pulses of admixture, remain methodologically challenging to reconstruct, especially when large datasets are unavailable. We develop an Approximate Bayesian Computations (ABC) framework to reconstruct complex admixture histories from independent genetic markers. We built the software package MetHis to simulate independent SNPs in a two-way admixed population for scenarios with multiple admixture pulses, or monotonically decreasing or increasing admixture at each generation; drawing model-parameter values from prior distributions set by the user. For each simulated dataset, we calculate 24 summary statistics describing genetic diversity and moments of individual admixture fraction. We coupled MetHis with existing ABC algorithms and investigate the admixture history of an African American and a Barbadian population. Results show that Random-Forest ABC scenario-choice, followed by Neural-Network ABC posterior parameter estimation, can distinguish most complex admixture scenarios and provide accurate model-parameter estimations. For both admixed populations, we find that monotonically decreasing contributions over time, from the European and African sources, explain the observed data more accurately than multiple admixture pulses. Furthermore, we find contrasted trajectories of introgression decay from the European and African sources between the two admixed populations. This approach will allow for reconstructing detailed admixture histories in numerous populations and species, particularly when maximum-likelihood methods are intractable.

genetics↗