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Jiggins, F. M.

Publications and source records attributed to Jiggins, F. M..

18 recordsLinked to original sources

Evolutionary genomics of a natural Wolbachia superinfection in the dengue mosquito Aedes albopictus

Aedes albopictus, an invasive mosquito vector of human pathogens, is naturally infected by two strains of the endosymbiotic bacterium Wolbachia, wAlbA and wAlbB. Here, we present a comprehensive genomic analysis of these Wolbachia strains, their associated plasmids, and host mitochondrial DNA (mtDNA). We observed extensive variation in Wolbachia densities--spanning over three orders of magnitude--indicating that infections often exist at extremely low levels and this variation is largely driven by environmental factors. Phylogenetic analyses revealed concordant evolutionary histories among mitochondrial, Wolbachia, and plasmid genomes, with no strong evidence for horizontal or paternal transmission. We estimate that the common ancestor of the superinfection existed [~]6,000--9,000 years ago. Patterns of genetic structure and divergence indicate that the subsequent geographical spread of Wolbachia has mirrored host population history. Comparative rate analyses revealed that wAlbA evolves more slowly than wAlbB, consistent with a reduced mutation rate. Despite the close relationship between wAlbB lineages, gene content in this strain is highly variable, with 184 genes exhibiting presence-absence or copy number variation across strains, including genes involved in inducing cytoplasmic incompatibility. Several of these genes reside in repetitive or prophage regions, indicating that transposable elements appear to drive structural genomic variation in Wolbachia populations. Together, our results highlight extensive natural diversity within Wolbachia populations and provide a foundation for understanding symbiont dynamics in nature and to inform the selection of strains for Wolbachia-based vector control programs.

evolutionary biology↗

Drosophila-virus genotype interactions dominate transmission, virulence and load, eroding additive fitness variance

Host-parasite coevolution is expected to generate strong selection for susceptibility and infectivity that has the potential to erode genetic variation. Despite this, natural populations often retain extensive genetic variation in these traits. Negative frequency-dependent selection could explain the maintenance of variation since it results in genotype-by-genotype interactions on fitness that, unlike additive genetic variance among hosts and pathogens, is masked from selection and so can remain cryptic. Here we combine coevolutionary modelling with large-scale experimental infection assays to quantify how host-pathogen interactions structure fitness variance in a vertically transmitted virus system, Drosophila melanogaster and sigma virus. Simulations show that coevolution typically erodes additive genetic variance in host and pathogen fitness, concentrating variance in host-virus interaction terms. Consistent with these predictions, experiments spanning 90 host-virus genotype combinations reveal that transmission, viral load and virulence are overwhelmingly governed by host-virus genetic interactions rather than host or virus main (i.e., additive) effects. As a result, neither host resistance alleles nor viral genotypes confer consistently higher fitness across genetic backgrounds. Interactions tend to be sex-specific, further limiting heritable fitness variation. Our results demonstrate that coevolution can substantially mask heritable genetic variation from selection by rendering fitness context dependent. This extensive cryptic genetic variation may be revealed either when ecological or evolutionary conditions shift, or when the process of coevolution itself alters the direction of selection. This demonstrates the need to account for genotype-specific interactions when forecasting evolutionary responses.

evolutionary biology↗

MHC-I diversity enables rapid adaptation during viral pandemic in wild rabbit populations

Emerging diseases can have devastating consequences for wild species, with long-term effects depending on the ability of the host to evolve resistance. Here, we show that major histocompatibility complex (MHC) genes provided standing genetic variation that enabled rabbits to mount a rapid evolutionary response to the myxoma virus pandemic that began in the 1950s. Using historical and modern specimens starting in 1865 and spanning the pandemic, we found strong parallel shifts in MHC-I allele frequencies across Australia, Britain and France, alongside population-specific signals. These evolutionary shifts appear to have altered antigen presentation to T cells. Our results provide evidence that MHC-I is under strong selection in natural populations during a pandemic, and that the high polymorphism of MHC may have contributed to the evolutionary rescue of these populations.

evolutionary biology↗

A humoral immune response to parasitoid wasps in Drosophila is regulated by JAK/STAT, NF-κB and GATA

The two arms of innate immunity consist of the cell-mediated cellular defenses and the systemic humoral immune responses. Drosophila humoral immune defenses in the context of antimicrobial immunity, particularly the regulation and activation of antimicrobial peptide secretion from the fat body, have been studied extensively. How Drosophila regulates humoral immunity against another major natural enemy, the parasitoid wasp, is less well-characterized. In this study, we focused on a gene crucial in anti-parasitoid immunity, lectin-24A, which is specifically induced following parasitization. We found that a fluorescent reporter driven by the region upstream of lectin-24A showed localized posterior expression in the larval fat body, the Drosophila tissue mediating humoral immunity. Furthermore, with RNA sequencing of the anterior and posterior fat body sections, we found that components of JAK/STAT, GATA, and Toll pathways were regulated differentially in the anterior-posterior axis of the fat body and/or by infection. Predicted binding motifs for transcription factors in all three of these pathways were identified in the 444bp upstream region of the lectin-24A gene, where scrambling these motifs leads to reduced basal or induced expression of the fluorescent reporter. Investigating each of these pathways, we found that JAK/STAT, the GATA factor Pannier, and the NF-{kappa}B factor dorsal all modulate the expression of lectin-24A. The binding motifs associated with these transcription factors were also enriched in the upstream sequences of parasitism-induced genes in the fat body. Taken together, these results indicate that JAK/STAT, Pannier, and NF-{kappa}B signaling are involved in the regulation of lectin-24A and, more generally, Drosophila humoral anti-parasitoid immunity after infection.

immunology↗

The evolution of constitutively active humoral immune defenses in Drosophila populations under high parasite pressure

Both constitutive and inducible immune mechanisms are employed by hosts for defense against infection. Constitutive immunity allows for a faster response, but it comes with an associated cost that is always present. This trade-off between speed and fitness costs leads to the theoretical prediction that constitutive immunity will be favored where parasite exposure is frequent. We selected populations of Drosophila melanogaster under high parasite pressure from the parasitoid wasp Leptopilina boulardi. With RNA sequencing, we found the evolution of resistance in these populations was associated with them developing constitutively active humoral immunity, mediated by the larval fat body. Furthermore, these evolved populations were also able to induce gene expression in response to infection to a greater level, which indicates an overall more activated humoral immune response to parasitization. The anti-parasitoid immune response also relies on the JAK/STAT signaling pathway being activated in muscles following infection, and this induced response was only seen in populations that had evolved under high parasite pressure. We found that the cytokine Upd3, which induces this JAK/STAT response, is being expressed by immature lamellocytes. Furthermore, these immune cells became constitutively present when populations evolved resistance, potentially explaining why they gained the ability to activate JAK/STAT signaling. Thus, under intense parasitism, populations evolved resistance by increasing both constitutive and induced immune defenses, and there is likely an interplay between these two forms of immunity. Author SummaryImmune defenses can be induced after infection or they may be constitutively active, even in uninfected individuals. As constitutive immunity is a more rapid response, theory predicts that it will be favored when animals frequently encounter parasites. When we subjected populations of Drosophila melanogaster to high rates of parasitization from its natural parasite, Leptopilina boulardi parasitoid wasps, we indeed observed that the immune response became constitutively active. Uninfected insects had an activated humoral immune response and produced cytokine-secreting immune cells that were normally induced after infection. However, we also found that these populations evolved a greater induced response. This included a greatly increased cytokine response after infection, suggesting that the constitutive activation of some aspects of the immune system may allow a greater induced response in other tissues.

evolutionary biology↗

Hunting Drosophila viruses from wild populations: a novel isolation approach and characterisation of viruses

Metagenomic studies have demonstrated that viruses are extremely diverse and abundant in insects, but the difficulty of isolating them means little is known about the biology of these newly discovered viruses. To overcome this challenge in Drosophila, we created a cell line with increased susceptibility to infection and detected novel viruses by the presence of double-stranded RNA. We demonstrate the utility of these tools by isolating La Jolla virus (LJV) and Newfield virus (NFV) from several wild Drosophila populations. These viruses have different potential host ranges, with distinct abilities to replicate in five Drosophila species. Similarly, in some species they cause high mortality and in others they are comparatively benign. In three species, NFV but not LJV caused large declines in female fecundity. This sterilization effect was associated with differences in tissue tropism, as NFV but not LJV was able to infect Drosophila melanogaster ovaries. We saw a similar effect in the invasive pest of fruit crops Drosophila suzukii, where oral infection with NFV caused reductions in the fecundity, suggesting it has potential as a biocontrol agent. In conclusion, a simple protocol allowed us to isolate new viruses and demonstrate that viruses identified by metagenomics have a large effect on the fitness of the model organism D. melanogaster and related species.

evolutionary biology↗

Developing Wolbachia-based disease interventions for an extreme environment

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced mosquito heat tolerance and egg viability, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.

evolutionary biology↗

Recognition of non-self is necessary to activate Drosophila's immune response against an insect parasite

Innate immune responses can be activated by pathogen-associated molecular patterns (PAMPs) or danger signals released by damaged tissues. As PAMPs are typically conserved across broad groups of pathogens but absent from the host, it is unclear whether they allow hosts to recognize parasites that are phylogenetically related to themselves, such as parasitoid wasps infecting insects. Parasitoids must penetrate the cuticle of Drosophila larvae to inject their eggs. In line with previous results, we find that the danger signal of wounding triggers the differentiation of specialized immune cells called lamellocytes. However, using oil droplets to mimic infection by a parasitoid wasp egg, we find that the activation of melanization response that kills parasitoids also requires exposure to a parasitoid wasp molecule that acts as a PAMP. The unidentified factor enhances the transcriptional response in hemocytes and induces a specific response in the fat body that includes Tep1, which is essential for efficient melanization. We conclude that a combination of danger signals and PAMPs are required activate Drosophilas immune response against parasitic insects.

immunology↗

Recurrent loss of an immunity gene that protects Drosophila against a major natural parasite

Polymorphisms in immunity genes can have large effects on susceptibility to infection. To understand the origins of this variation, we investigated the genetic basis of resistance to the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster. A cis-regulatory polymorphism in the gene Lectin-24A abolishes expression after infection, strongly reducing survival. Other null mutations have arisen repeatedly in this gene, with additional loss-of-expression and premature stop codons segregating in nature. The frequency of these alleles varies greatly, and in some populations natural selection has driven them near to fixation. We conclude that there is a pleiotropic cost to Lectin-24A expression, and in some populations this outweighs the benefit of resistance, resulting in natural selection causing the repeated loss of this important immune defense. Significance StatementGenetic differences between individuals can have a large effect on susceptibility to infectious disease. We have identified a gene called Lectin-24A that is important in the immune response that protects fruit flies against one of their main natural enemies--parasitic wasps. However, in nature many flies carry mutated copies of this gene that are no longer functional. We found that the high frequency of these loss-of-function mutations can only be explained if they have a selective advantage in some populations. Therefore, we can conclude that this immune defiance is costly, and genetic variation in susceptibility is maintained because in some locations susceptible flies are fitter than resistant flies.

evolutionary biology↗

DROP: Molecular voucher database for identification of Drosophila parasitoids

Molecular identification is increasingly used to speed up biodiversity surveys and laboratory experiments. However, many groups of organisms cannot be reliably identified using standard databases such as GenBank or BOLD due to lack of sequenced voucher specimens identified by experts. Sometimes a large number of sequences are available, but with too many errors to allow identification. Here we address this problem for parasitoids of Drosophila by introducing a curated open-access molecular reference database, DROP (Drosophila parasitoids). Identifying Drosophila parasitoids is challenging and poses a major impediment to realize the full potential of this model system in studies ranging from molecular mechanisms to food webs, and in biological control of Drosophila suzukii. In DROP (http://doi.org/10.5281/zenodo.4519656), genetic data are linked to voucher specimens and, where possible, the voucher specimens are identified by taxonomists and vetted through direct comparison with primary type material. To initiate DROP, we curated 154 laboratory strains, 856 vouchers, 554 DNA sequences, 16 genomes, 14 transcriptomes, and 6 proteomes drawn from a total of 183 operational taxonomic units (OTUs): 114 described Drosophila parasitoid species and 69 provisional species. We found species richness of Drosophila parasitoids to be heavily underestimated and provide an updated taxonomic catalogue for the community. DROP offers accurate molecular identification and improves cross-referencing between individual studies that we hope will catalyze research on this diverse and fascinating model system. Our effort should also serve as an example for researchers facing similar molecular identification problems in other groups of organisms.

genomics↗

Constitutive activation of cellular immunity underlies the evolution of resistance to infection

Organisms rely on inducible and constitutive immune defences to combat infection. Constitutive immunity enables a rapid response to infection but may carry a cost for uninfected individuals, leading to the prediction that it will be favoured when infection rates are high. When we exposed populations of Drosophila melanogaster to intense parasitism by the parasitoid wasp Leptopilina boulardi, they evolved resistance by developing a more reactive cellular immune response. Using single-cell RNA sequencing, we found that immune-inducible genes had become constitutively upregulated. This was the result of resistant larvae differentiating precursors of specialized immune cells called lamellocytes that were previously only produced after infection. Therefore, populations evolved resistance by genetically hard-wiring an induced immune response to become constitutive.

evolutionary biology↗

Widespread conservation and lineage-specific diversification of genome-wide DNA methylation patterns across arthropods

Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed genes, with both intergenic regions and transposable elements (TEs) depleted of methylation. The evolutionary origin and the function of these methylation patterns are poorly understood. Here we characterise the evolution of DNA methylation across the arthropod phylum. While the common ancestor of the arthropods had low levels of TE methylation and did not methylate promoters, both of these functions have evolved independently in centipedes and mealybugs. In contrast, methylation of the exons of a subset of transcribed genes is ancestral and widely conserved across the phylum, but has been lost in specific lineages. Remarkably the same set of genes are likely to be methylated in all species that retained exon-enriched methylation. We show that these genes have characteristic patterns of expression correlating to broad transcription initiation sites and well-positioned nucleosomes, providing new insights into potential mechanisms driving methylation patterns over hundreds of millions of years. Author SummaryAnimals develop from a single cell to form a complex organism with many specialised cells. Almost all of the fantastic variety of cells must have the same sequence of DNA, and yet they have distinct identities that are preserved even when they divide. This remarkable process is achieved by turning different sets of genes on or off in different types of cell using molecular mechanisms known as "epigenetic gene regulation". Surprisingly, though all animals need epigenetic gene regulation, there is a huge diversity in the mechanisms that they use. Characterising and explaining this diversity is crucial in understanding the functions of epigenetic pathways, many of which have key roles in human disease. We studied how one particular type of epigenetic regulation, known as DNA methylation, has evolved within arthropods. Arthropods are an extraordinarily diverse group of animals ranging from horseshoe crabs to fruit flies. We discovered that the levels of DNA methylation and where it is found within the genome changes rapidly throughout arthropod evolution. Nevertheless, there are some features of DNA methylation that seem to be the same across most arthropods-in particular we found that there is a tendency for a similar set of genes to acquire methylation of DNA in most arthropods, and that this is conserved over 350 million years. We discovered that these genes have distinct features that might explain how methylation gets targeted. Our work provides important new insights into the evolution of DNA methylation and gives some new hints to its essential functions.

genetics↗

Wolbachia affect behavior and possibly reproductive compatibility but not thermoresistance, fecundity, and morphology in a novel transinfected host, Drosophila nigrosparsa

Wolbachia, intracellular endosymbionts, are estimated to infect about half of all arthropod species. These bacteria manipulate their hosts in various ways for their maximum benefits. The rising global temperature may accelerate species migration and, thus, horizontal transfer of Wolbachia may occur across species previously not in contact. We transinfected and then cured the alpine fly Drosophila nigrosparsa with Wolbachia strain wMel to study its effects on this species. We found low Wolbachia titer, possibly cytoplasmic incompatibility, and an increase in locomotion of both infected larvae and adults compared with cured ones. However, no change in fecundity, no impact on heat and cold tolerance, and no change in wing morphology were observed. Although Wolbachia increased locomotor activities in this species, we conclude that D. nigrosparsa may not benefit from the infection. Still, D. nigrosparsa can serve as a host for Wolbachia because vertical transmission is possible but may not be as high as in the native host of wMel, Drosophila melanogaster.

ecology↗

Host-pathogen coevolution increases genetic variation in susceptibility to infection

It is common to find considerable genetic variation in susceptibility to infection in natural populations. We have investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, we always found greater genetic variation in susceptibility to viruses that had coevolved with their host. We went on to examine the genetic architecture of resistance in one host species, finding that there are more major-effect genetic variants in coevolved host-parasite interactions. We conclude that selection by pathogens increases genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations.

evolutionary biology↗

Host shifts result in parallel genetic changes when viruses adapt to closely related species

Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease.

evolutionary biology↗

Pan-arthropod analysis reveals somatic piRNAs as an ancestral TE defence

In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were likely present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and mRNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders, scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

evolutionary biology↗

Complex Coding And Regulatory Polymorphisms In A Restriction Factor Determine The Susceptibility Of Drosophila To Viral Infection

It is common to find that major-effect genes are an important cause of variation in susceptibility to infection. Here we have characterised natural variation in a gene called pastrel that explains over half of the genetic variance in susceptibility to the virus DCV in populations of Drosophila melanogaster. We found extensive allelic heterogeneity, with a sample of seven alleles of pastrel from around the world conferring four phenotypically distinct levels of resistance. By modifying candidate SNPs in transgenic flies, we show that the largest effect is caused by an amino acid polymorphism that arose when an ancestral threonine was mutated to alanine, greatly increasing resistance to DCV. Overexpression of the ancestral susceptible allele provides strong protection against DCV, indicating that this mutation acted to improve an existing restriction factor. The pastrel locus also contains complex structural variation and cis-regulatory polymorphisms altering gene expression. We find that higher expression of pastrel is associated with increased survival after DCV infection. To understand why this variation is maintained in populations, we investigated genetic variation surrounding the amino acid variant that is causing flies to be resistant. We found no evidence of natural selection causing either recent changes in allele frequency or geographical variation in frequency, suggesting that this is an old polymorphism that has been maintained at a stable frequency. Overall, our data demonstrate how complex genetic variation at a single locus can control susceptibility to a virulent natural pathogen.

evolutionary biology↗

Vertically transmitted rhabdoviruses are found across three insect families and have dynamic interactions with their hosts

A small number of free-living viruses have been found to be obligately vertically transmitted, but it remains uncertain how widespread vertically transmitted viruses are and how quickly they can spread through host populations. Recent metagenomic studies have found several insects to be infected with sigma viruses (Rhabdoviridae). Here, we report that sigma viruses that infect Mediterranean fruit flies (Ceratitis capitata), Drosophila immigrans, and speckled wood butterflies (Pararge aegeria) are all vertically transmitted. We find patterns of vertical transmission that are consistent with those seen in Drosophila sigma viruses, with high rates of maternal transmission, and lower rates of paternal transmission. This mode of transmission allows them to spread rapidly in populations, and using viral sequence data we found the viruses in D. immigrans and C. capitata had both recently swept through host populations. The viruses were common in nature, with mean prevalences of 12% in C. capitata, 38% in D. immigrans and 74% in P. aegeria. We conclude that vertically transmitted rhabdoviruses may be widespread in insects, and that these viruses can have dynamic interactions with their hosts.

evolutionary biology↗