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Evanno, G.

Publications and source records attributed to Evanno, G..

12 recordsLinked to original sources

Dispersal, gene flow and adaptive differentiation in hierarchically structured populations

The balance between local adaptation and gene flow is rarely quantified when populations are hierarchically differentiated across multiple spatial scales. We addressed this gap in Atlantic salmon (Salmo salar) at its southern range edge, using 1342 individuals from 21 rivers along the French Atlantic and Channel coasts with a 60k SNP array, and combining estimates of dispersal with genome-wide scans for adaptive differentiation across spatial scales. Population structure was hierarchical, resolving five genetic clusters with differentiation among groups five times higher than among populations within them. Assignment tests revealed a marked contrast between clusters, but unassigned individuals reached very high proportions within some clusters, indicating that gene flow has already blurred among-populations differences. Adaptive differentiation was detected among and within clusters, but the loci involved overlapped only partially across scales and among clusters, indicating that adaptation at each hierarchical level relies on distinct sets of variants. Dispersal was a poor guide to where this signal persisted: retaining putative dispersers reduced the candidate set more than threefold, showing that immigrant genotypes could dilute among-populations allele-frequency contrasts within a single generation. Yet differentiation among populations remained strong, as expected if dispersers reproduce poorly. Resolving the balance between local adaptation and gene flow therefore requires accounting for dispersal and adaptive differentiation at different spatial scales, with direct implications for conserving hierarchically structured populations at climatically vulnerable range edges.

evolutionary biology↗

A mosaic of genomic architectures underpins parasitism loss in a jawless vertebrate

Lampreys are the only ancestrally parasitic vertebrate lineage, yet parasitism has been repeatedly lost alongside a suite of life-history changes, such as loss of migration and juvenile feeding and accelerated maturation. Combining whole-genome resequencing, haplotype-resolved assemblies, hybrid-zone genotyping, multi-tissue transcriptomics, and sperm phenotyping, we map this life-history syndrome in European Lampetra to six chromosomes spanning a mosaic of genomic architectures: a [~]20 Mb low-recombination region on chromosome 1 lacking chromosomal rearrangements within Lampetra but involving inter-specific rearrangements across deep lamprey lineages; a translocated inversion with ecotype-dependent sperm-velocity effects; and ecotype-divergent deletions overlapping genes crucial for nervous system (CNTNAP2) and reproductive development (FSHR). However, this genomic basis is not shared with a convergent sister lineage, pointing to independent routes to a recurring life-history transition in lampreys.

evolutionary biology↗

Early life thermal plasticity and adaptive divergence among populations of Arctic charr (Salvelinus alpinus)

Climate warming alters the thermal environment experienced by ectotherms, whose physiological performance and fitness are constrained by temperature. Early life stages are often the temperature-sensitive phases of the life cycle, particularly in freshwater stenotherms such as the Arctic charr (Salvelinus alpinus). In this study, we used a common garden approach to compare the response and phenotypic plasticity of four charr populations to warmer conditions. These populations inhabit thermally contrasted lakes, including both native and introduced populations. We reared embryos at either an optimal (5{degrees}C) or a warmer (8.5{degrees}C) temperature. We tested adaptive divergence among populations in four traits (survival, incubation duration, body length and yolk sac volume) using Qst - Fst comparisons. We found that warmer temperature reduced body size, survival and incubation time, while thermal reaction norms differed among populations. Unexpectedly, populations originating from warmer environments did not consistently exhibit higher trait values under elevated temperatures. In contrast, the colder high-altitude population exhibited higher survival rates and lower yolk reserves for a given size under heat stress than the other populations. Our results highlight substantial variation among populations in responses to heat stress, emphasizing the complexity of predicting population responses to climate warming.

evolutionary biology↗

Selection against dispersers: Sex, age and origin-dependent fitness differences in wild Atlantic salmon

Local adaptation is often portrayed as uniform fitness disadvantages of immigrants relative to residents. Yet dispersal costs vary with origin, sex, and life-history traits, shaping the balance between gene flow and adaptation. We quantified these heterogeneous costs by comparing the reproductive success of local and immigrant individuals using a 15-year genetic pedigree of Atlantic salmon (Salmo salar), including over 1,100 adults and 3,400 juveniles. Immigrants represented 19.5% of adults, showed male-biased dispersal, and averaged 15% lower reproductive success than locals. However, outcomes were strongly origin-dependent: immigrants from some populations suffered severe fitness costs while others matched or exceeded locals. Sex and life-history further modulated reproductive success: male immigrants underperformed local males, whereas multi-sea-winter females often equaled or outperformed female residents. Immigrant males partially compensated their fitness offset by acquiring more mates. These findings highlight that, while local adaptation promotes philopatry, immigrants origin effects should be considered in gene-flow adaptation dynamics.

evolutionary biology↗

The chalk streams of southern England and northern France harbour substantial unique components of the overall genetic diversity of Atlantic salmon (Salmo salar L.)

Populations of Atlantic salmon continue to suffer marked declines in abundance due to stressors acting in both their freshwater and marine habitats. It is therefore an imperative to identify populations in need of increased conservation intervention, with the aim of preserving as much as possible the genetic diversity present within the species. Previous microsatellite-based analyses have shown the chalk rivers of southern England and northern France to hold genetically distinct populations of salmon. However, these salmon populations have never been investigated in the same study. Using a suite of 93 single nucleotide polymorphism loci and samples from 42 British Isles and French rivers, we demonstrate the French and English chalk salmon to be closely related and distinct from salmon inhabiting non-chalk rivers. The identification of a small number of significant FST outliers suggests that this distinction is driven by local adaptation. We propose that the chalk and non-chalk salmon be designated as two distinct Evolutionarily Significant Units that each contain multiple Management Units. The chalk river salmon, especially those from southern England, are identified as making a significant contribution to the overall diversity of the species within the English Channel region. As a consequence, we propose that the salmon populations of the chalk streams may meet the criteria for recognition as a distinct subspecies of salmon, Salmo salar calcariensis. Taken together, the results presented here highlight the urgent need for enhanced conservation and protection for the Atlantic salmon populations inhabiting the chalk rivers of southern England and northern France.

evolutionary biology↗

A century of allopatry: plasticity and rapid selection shape phenotypic trait variability under contrasting environments.

Allopatric isolation under contrasting environments can drive rapid phenotypic divergence, even over contemporary timescales. Rapid changes in morphology or physiology can allow organisms to adapt to biotic and abiotic characteristics of their habitats. While studying metabolism, growth and resources needs may allow to understand adaptation to several selective pressures, these traits are rarely jointly considered. We investigated morphological, growth, and metabolic divergence in two allopatric populations of Arctic charr (Salvelinus alpinus) sharing a common evolutionary origin but inhabiting contrasting environments. We combined field observations, common garden and quantitative genetic approaches to disentangle contributions of genetic divergence and plasticity to phenotypic variability. Wild adults differed in body shape and growth trajectories, potentially reflecting plasticity related to resource availability and temperature variations. Under common garden conditions, juveniles displayed inter-population differences in routine metabolic rate, its allometric scaling with body mass. These patterns suggest divergent selection on physiological traits. Despite low neutral genetic differentiation, phenotypic divergence unfolded in fewer than 100 years, suggesting that plasticity and selection can promote rapid multi-trait changes. These findings highlight that considering changes in physiological, growth and morphological traits can reveal the adaptive potential of small, isolated populations facing rapid environmental change.

evolutionary biology↗

LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation

Anti-thymocyte/lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because of animal origin, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated with subclinical inflammatory events possibly impacting long-term graft survival. Their strong and long-lasting lymphodepleting activity also increases the risk for infections. To circumvent these drawbacks, LIS1 has been engineered as a glyco-humanized polyclonal antibody obtained by immunizing genetically modified pigs knocked out for major xeno-antigens Gal and Neu5Gc. It is Fc-silenced in humans and differs from other ATGs/ALGs by its mechanism of action excluding antibody-dependent cell-mediated cytotoxicity and being restricted to complement and phagocyte-mediated cytotoxicity, apoptosis and antigen masking, resulting in profound inhibition of T-cell alloreactivity in mixed-leucocyte-reactions. Preclinical evaluation in macaques showed that LIS1 impacted CD4+, CD8+ effector T cells but not T-reg, B cells or myeloid cells. Compared with rabbit ATG, LIS1 induced transient depletion of target T cells in the peripheral blood but was equivalent in preventing allograft rejection in a skin allograft model. The novel therapeutic modality of LIS1 might present advantages in induction treatment after organ transplantation by shortening the T-cell depletion period while maintaining adequate immunosuppression and reducing immunogenicity.

immunology↗

Anti-SARS-CoV-2 swine glyco-humanized polyclonal antibody XAV-19 retains neutralizing activity against SARS-CoV-2 B.1.1.529 (Omicron)

B.1.1.529 is the SARS-CoV-2 variant designated Omicron by the WHO in November 2021. It is a highly divergent variant with a high number of mutations, including 26-32 mutations in the spike protein among which 15 in the Receptor Binding Domain (RBD) including at the human angiotensin converting enzyme 2 (ACE-2) receptor interacting interface. Because of a decreased affinity for the ACE-2 receptor and a geometric reorganization of the S1-S2 cleavage site, the Omicron variant is predicted to not have a significant infectivity advantage over the delta variant and to be less pathogenic than Delta. However, in Omicron, neutralizing epitopes are greatly affected, suggesting that current vaccines and neutralizing monoclonal antibodies might confer reduced protection against this variant. In contrast, we and others previously demonstrated that polyclonal antibodies against SARS-CoV-2 RBD obtained from hyperimmunized animal hosts do maintain their neutralizing properties against Alpha to Delta. Here, we confirmed these findings by showing that XAV-19, a swine glyco-humanized polyclonal antibody retains full neutralizing activity against Omicron.

immunology↗

Population genetics reveals cryptic lineages and ongoing hybridization in a declining migratory fish species complex

Deciphering the effects of historical and recent demographic processes responsible for the spatial patterns of genetic diversity and structure is a key objective in evolutionary and conservation biology. Using population genetic analyses, we investigated the demographic history, the contemporary genetic diversity and structure, and the occurrence of hybridization and introgression of two species of anadromous fish with contrasting life history strategies and which have undergone recent demographic declines, the allis shad (Alosa alosa) and the twaite shad (Alosa fallax). We genotyped 706 individuals from 20 rivers and 5 sites at sea in Southern Europe at thirteen microsatellite markers. Genetic structure between populations was lower for the nearly semelparous species A. alosa, which disperses greater distances compared to the iteroparous species, A. fallax. Individuals caught at sea were assigned at the river level for A. fallax and at the region level for A. alosa. Using an approximate Bayesian computation framework, we inferred that the most likely long term historical divergence scenario between both species and lineages involved historical separation followed by secondary contact accompanied by strong population size decline. Accordingly, we found evidence for contemporary hybridization and bidirectional introgression due to gene flow between both species and lineages. Moreover, our results support the existence of at least one distinct species in the Mediterrannean sea: A. agone in Golfe du Lion area, and another divergent lineage in Corsica. Overall, our results shed light on the interplay between historical and recent demographic processes and life history strategies in shaping population genetic diversity and structure of closely related species. The recent demographic decline of these species populations and their hybridization should be carefully considered while implementing conservation programs.

evolutionary biology↗

XAV-19, a novel swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike, efficiently neutralizes B.1.1.7 British and B.1.351 South-African variants.

Amino acid substitutions and deletions in Spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBM), in direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Therefore, in Spike/ACE2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study with the Beta strain on Vero E6 cells conducted over 1 month, no mutation was associated with addition of increasing doses XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in a phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (Covid-19) including the different variants of concern identified so far.

immunology↗

High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Many monoclonal antibodies (mAbs) have been developed but appear insufficient to neutralize SARS-CoV-2 unless two or three of them are being combined. Therefore, heterologous polyclonal antibodies of animal origin, that have been used for decades to fight against infectious agents might represent a highly efficient alternative to the use of CP or mAbs in COVID-19 by targeting multiple antigen epitopes. However, conventional heterologous polyclonal antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrate epitopes, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the Gal 1,3-galactose (Gal), ultimately forming immune complexes and potentially leading to serum sickness or allergy. To circumvent these drawbacks, we engineered animals lacking the genes coding for the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) and 1,3-galactosyl-transferase (GGTA1) enzymes to produce glyco-humanized polyclonal antibodies (GH-pAb) lacking Neu5Gc and -Gal epitopes. We found that pig IgG Fc domains fail to interact with human Fc receptors and thereby should confer the safety advantage to avoiding macrophage dependent exacerbated inflammatory responses, a drawback possibly associated with antibody responses against SARS-CoV-2 or to avoiding a possible antibody-dependent enhancement (ADE). Therefore, we immunized CMAH/GGTA1 double knockout (DKO) pigs with the SARS-CoV-2 spike receptor-binding domain (RBD) to elicit neutralizing antibodies. Animals rapidly developed a hyperimmune response with anti-SARS-CoV-2 end-titers binding dilutions over one to a million and end-titers neutralizing dilutions of 1:10,000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized Spike/angiotensin converting enzyme-2 (ACE-2) interaction at a concentration < 1g/mL and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. These data and the accumulating safety advantages of using glyco-humanized swine antibodies in humans warranted clinical assessment of XAV-19 to fight against COVID-19.

immunology↗

Riverscape genetics in brook lamprey: genetic diversity is less influenced by river fragmentation than by gene flow with the anadromous ecotype

Understanding the effect of human induced landscape fragmentation on gene flow and evolutionary potential of wild populations has become a major concern. Here, we investigated the effect of riverscape fragmentation on patterns of genetic diversity in the freshwater resident brook lamprey (Lampetra planeri) that has a low ability to pass obstacles to migration. We also tested the hypotheses of i) asymmetric gene flow following water current and ii) admixture with the closely related anadromous L. fluviatilis ecotype having a positive effect on L. planeri genetic diversity. We genotyped 2472 individuals, including 225 L. fluviatilis, sampled in 81 sites upstream and downstream from barriers to migration, in 29 West-European rivers. Linear modelling revealed a strong positive relationship between the distance to the source and genetic diversity, consistent with expected patterns of decreased gene flow into upstream populations. However, the presence of anthropogenic barriers had a moderate effect on spatial genetic structure. Accordingly, we found evidence for downstream-directed gene flow, supporting the hypothesis that barriers do not limit dispersal following water flow. Downstream L. planeri populations in sympatry with L. fluviatilis displayed consistently higher genetic diversity. We conclude that genetic drift and slight downstream gene flow mainly drive the genetic make up of upstream L. planeri populations whereas admixture between ecotypes maintains higher levels of genetic diversity in L. planeri populations sympatric with L. fluviatilis. We discuss the implications of these results for the design of conservation strategies of lamprey, and other freshwater organisms with several ecotypes, in fragmented dendritic river networks.

evolutionary biology↗