Biology subjects

Daron, J.

Publications and source records attributed to Daron, J..

11 recordsLinked to original sources

bioRxiv2025

A targeted amplicon sequencing panel for cost-effective high-throughput genotyping of Aedes aegypti

The mosquito Aedes aegypti is the primary vector for several medically significant arboviruses, including dengue, Zika, chikungunya, and yellow fever. Studying the genetic diversity of Ae. aegypti is crucial for understanding its evolutionary history, population dynamics, and the effectiveness of vector control methods. Due to the large genome size of Ae. aegypti, whole-genome sequencing (WGS) is often cost-prohibitive for large-scale studies. Recent advances in reduced-representation methods, aiming to reduce costs by sequencing only a small portion of the genome, provide cost-effective alternatives. However, a standardized set of genome-wide markers specifically designed for population genetic studies of Ae. aegypti remains unavailable. Here, we present a targeted amplicon sequencing panel designed for cost-effective, high-throughput genotyping across 291 loci distributed throughout the Ae. aegypti genome. Our in silico analyses indicate that this amplicon panel effectively replicates population structure analyses typically derived from WGS data. We demonstrate that the amplicon panel accurately discriminates between diverse laboratory colonies of Ae. aegypti and consistently measures individual genetic admixture to a degree comparable with WGS. By enabling high-throughput genotyping at a reduced cost, we anticipate that our targeted amplicon sequencing panel will facilitate large-scale genotyping studies of Ae. aegypti for vector surveillance and population structure analyses, especially in resource-limited settings.

genomics↗

bioRxiv2025

Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 variants

The mosquito Aedes aegypti is the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wild Ae. aegypti populations is governed by genetic factors, but specific causal variants are unknown. Here, we identify a cytochrome P450-encoding gene (CYP4G15) whose variants drive differences in DENV susceptibility in a natural Ae. aegypti population. CYP4G15 is transiently upregulated in DENV-resistant midguts, while knockdown increases susceptibility, and transgenic overexpression enhances resistance. A naturally occurring 18-base-pair promoter deletion reduces CYP4G15 expression and confers higher DENV susceptibility. The unexpected role of a cytochrome P450 in DENV susceptibility challenges the long-standing focus on canonical immune pathways and opens new avenues for understanding antiviral defense and DENV transmission in mosquitoes.

microbiology↗

bioRxiv2024

Limited impact of the siRNA pathway on transposable element expression in Aedes aegypti

Transposable elements (TEs) are DNA sequences that can change their position within a genome. In the germline of arthropods, post-transcriptional regulation of TE expression is mainly mediated by the Piwi-interacting RNA (piRNA) pathway. piRNAs are small RNAs of 24-30 nucleotides (nt) in length produced from genomic precursor transcripts as well as through a ping-pong amplification cycle. In somatic tissues, certain insects, such as Drosophila, instead rely on the small interfering RNA (siRNA) pathway as a key regulator of TE expression. siRNAs are 21nt small RNAs produced from double-stranded RNA by the endonuclease Dicer2, which guides an RNA-induced silencing complex to degrade a complementary RNA. However, whether the siRNA pathway also regulates TE expression in the mosquito Aedes aegypti, a medically significant vector species with abundant somatic piRNAs, is unknown. To address this question, we investigated the expression of TEs and small RNAs in both somatic and gonadal tissues of a Dicer2 mutant line of Ae. aegypti and its wild-type counterpart. Our results show a modified pattern of TE expression and a decrease in TE-derived 21nt small RNAs in the Dicer2 mutant, but no major shift of TE transcript abundance. The lack of a functional siRNA pathway also causes perturbations in piRNA ping-pong signatures and the expression of certain piRNA-associated genes, but without clear evidence for compensation by increased piRNA pathway activity. We conclude that the mosquito Ae. aegypti produces siRNAs targeting TEs but these lack a critical role in the regulation of TE expression both in somatic and in gonadal tissues.

genomics↗

bioRxiv2024

A Vago-like gene enhances dengue and Zika virus dissemination in Aedes aegypti

Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown. We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquitos body was slightly impaired, albeit not altering virus transmission rates. Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.

immunology↗

bioRxiv2024

Genomic Signatures of Microgeographic Adaptation in Anopheles coluzzii Along an Anthropogenic Gradient in Gabon

Species distributed across heterogeneous environments often evolve locally adapted populations, but understanding how these persist in the presence of homogenizing gene flow remains puzzling. In Gabon, Anopheles coluzzii, a major African malaria mosquito is found along an ecological gradient, including a sylvatic population, away of any human presence. This study identifies into the genomic signatures of local adaptation in populations from distinct environments including the urban area of Libreville, and two proximate sites 10km apart in the La Lope National Park (LLP), a village and its sylvatic neighborhood. Whole genome re-sequencing of 96 mosquitoes unveiled[~] 5.7millions high-quality single nucleotide polymorphisms. Coalescent-based demographic analyses suggest an[~] 8,000-year-old divergence between Libreville and La Lope populations, followed by a secondary contact ([~]4,000 ybp) resulting in asymmetric effective gene flow. The urban population displayed reduced effective size, evidence of inbreeding, and strong selection pressures for adaptation to urban settings, as suggested by the hard selective sweeps associated with genes involved in detoxification and insecticide resistance. In contrast, the two geographically proximate LLP populations showed larger effective sizes, and distinctive genomic differences in selective signals, notably soft-selective sweeps on the standing genetic variation. Although neutral loci and chromosomal inversions failed to discriminate between LLP populations, our findings support that microgeographic adaptation can swiftly emerge through selection on standing genetic variation despite high gene flow. This study contributes to the growing understanding of evolution of populations in heterogeneous environments amid ongoing gene flow and how major malaria mosquitoes adapt to human. SignificanceAnopheles coluzzii, a major African malaria vector, thrives from humid rainforests to dry savannahs and coastal areas. This ecological success is linked to its close association with domestic settings, with human playing significant roles in driving the recent urban evolution of this mosquito. Our research explores the assumption that these mosquitoes are strictly dependent on human habitats, by conducting whole-genome sequencing on An. coluzzii specimens from urban, rural, and sylvatic sites in Gabon. We found that urban mosquitoes show de novo genetic signatures of human-driven vector control, while rural and sylvatic mosquitoes exhibit distinctive genetic evidence of local adaptations derived from standing genetic variation. Understanding adaptation mechanisms of this mosquito is therefore crucial to predict evolution of vector control strategies.

evolutionary biology↗

bioRxiv2024

Atypical landscape of transposable elements in the large genome of Aedes aegypti

Transposable elements (TEs) contribute significantly to variation in genome size among eukaryotic species, but the factors influencing TE accumulation and diversification are only partially understood. Most of our current knowledge about TE organization, dynamics and evolution derives from investigations in model organisms with a relatively small genome size such as Drosophila melanogaster or Arabidopsis thaliana. Whether the observed patterns hold true in larger genomes remains to be determined. The Diptera order is an ideal taxon to address this question, because it includes a forty-year model of TE biology (D. melanogaster) as well as mosquito species with significantly larger genomes. Here, we use a comparative genomics approach to characterize the genomic forces that have shaped the TE content of the Aedes aegypti genome (1.3 Gb) relative to the Anopheles coluzzii genome (300 Mb) and the D. melanogaster genome (180 Mb). Leveraging a newly developed high-quality TE library for Ae. aegypti, our results reveal a contrasted pattern of TE organization in Ae. aegypti compared to An. coluzzii and D. melanogaster. Our analyses suggest that the substantial TE fraction observed in the Ae. aegypti genome reflect both a high rate of TE transposition and a low rate of TE elimination. Together, our results indicate that TE organization and evolutionary dynamics in the large genome of Ae. aegypti are distinct from those of other dipterans with smaller genomes.

evolutionary biology↗

bioRxiv2023

No Wolbachia protection against Plasmodium falciparum infection in the major malaria mosquito Anopheles moucheti

Since the discovery of natural malaria vector populations infected by the endosymbiont bacterium Wolbachia, a renewed interest has arisen for using this bacterium as an alternative for malaria control. Among naturally infected mosquitoes, Anopheles moucheti, a major malaria mosquito in Central Africa, exhibits one of the highest prevalences of Wolbachia infection. To better understand whether this maternally inherited bacterium could be used for malaria control, we investigated Wolbachia influence in An. moucheti populations naturally infected by the malaria parasite Plasmodium falciparum. To this end, we collected mosquitoes in a village from Cameroon, Central Africa, where this mosquito is the main malaria vector. We found that the prevalence of Wolbachia bacterium was almost fixed in the studied mosquito population, and was higher than previously recorded. We also quantified Wolbachia in whole mosquitoes and dissected abdomens, confirming that the bacterium is also elsewhere than in the abdomen, but at lower density. Finally, we analyzed the impact of Wolbachia presence and density on P. falciparum infection. Wolbachia density was slightly higher in mosquitoes infected with the malaria parasite than in uninfected mosquitoes. However, we observed no correlation between the P. falciparum and Wolbachia densities. In conclusion, our study indicates that naturally occurring Wolbachia infection does not affect P. falciparum development within An. moucheti mosquitoes.

microbiology↗

bioRxiv2022

Population genomic evidence of adaptive response during the invasion history of Plasmodium falciparum in the Americas

Plasmodium falciparum, the most virulent agent of human malaria, spread from Africa to all continents following the out-of-Africa human migrations. During the transatlantic slave trade between the 16th and 19th centuries, it was introduced twice independently to the Americas where it adapted to new environmental conditions (new human populations and mosquito species). Here, we analyzed the genome-wide polymorphisms of 2,635 isolates across the current P. falciparum distribution range in Africa, Asia, Oceania, and the Americas to investigate its genetic structure, invasion history, and selective pressures associated with its adaptation to the American environment. We confirmed that American populations originated from Africa with at least two independent introductions that led to two genetically distinct clusters, one in the North (Haiti and Columbia) and one in the South (French Guiana and Brazil), and the admixed Peruvian group. Genome scans revealed recent and more ancient signals of positive selection in the American populations. Particularly, we detected positive selection signals in genes involved in interactions with host (human and mosquito) cells and in genes involved in resistance to malaria drugs in both clusters. We found that some genes were under selection in both clusters. Analyses suggested that for five genes, adaptive introgression between clusters or selection on standing variation was at the origin of this repeated evolution. This study provides new genetic evidence on P. falciparum colonization history and on its local adaptation in the Americas.

evolutionary biology↗

bioRxiv2021

Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus within the Orthocoronavirinae causing an emergent infectious disease in humans, the ongoing coronavirus disease 2019 pandemic (COVID-19). Due to the high zoonotic potential of these viruses, it is critical to unravel their evolutionary history of host species shift, adaptation and emergence. Only such knowledge can guide virus discovery, surveillance and research efforts to identify viruses posing a pandemic risk in humans. We present a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium.

evolutionary biology↗

bioRxiv2020

Population genomic evidence of a Southeast Asian origin of Plasmodium vivax

Plasmodium vivax is the most prevalent and widespread human malaria parasite, with almost three billion people living at risk of infection. With the discovery of its closest genetic relatives in African great apes (Plasmodium vivax-like), the origin of P. vivax has been proposed to be located in the sub-Saharan African area. However, the limited number of genetic markers and samples investigated questioned the robustness of this result. Here, we examined the population genomic variation of 447 human P. vivax strains and 19 ape P. vivax-like strains originating from 24 different countries across the world. We identified 2,005,455 high quality single-nucleotide polymorphism loci allowing us to conduct an extensive characterization to date of P. vivax worldwide genetic variation. Phylogenetic relationships between human and ape Plasmodium revealed that P. vivax is a sister clade of P. vivax-like, not included within the radiation of P. vivax-like. By investigating a variety of aspects of P. vivax variation, we identified several striking geographical patterns in summary statistics as function of increasing geographic distance from Southeast Asia, suggesting that P. vivax may derived from serial founder effects from a single origin located in Asia.

evolutionary biology↗

bioRxiv2020

A new role for histone demethylases in the maintenance of plant genome integrity

Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development and adaptation to environmental fluctuations in most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in Arabidopsis, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play distinct roles in H3K27me3 and H3K27me1 homeostasis. We show that failure to reset these chromatin marks during sexual reproduction results in the inheritance of epigenetic imprints, which cause a loss of DNA methylation at heterochromatic loci and transposon activation. Thus, Jumonji-type histone demethylases in plants contribute towards maintaining distinct transcriptional states during development and help safeguard genome integrity following sexual reproduction.

plant biology↗