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Signor, S.

Publications and source records attributed to Signor, S..

17 recordsLinked to original sources

PeakLocus: A transcript-aware toolkit for RNA-Centric Genomic Annotation

Annotating genomic coordinates is an important step for identifying where along the transcript genomic features are enriched yet many widely used peak annotation tools were designed primarily around general genomic or chromatin features. We developed PeakLocus, a dependency-free Java command line tool that assigns RNA feature to transcript interval in an explicitly RNA centered transcript context. PeakLocus accepts bed-like and tabular interval files together with a gene transfer file as reference, detects coordinates and strand structure, and reports gene, transcript, biotype, and location information such as 5' UTR, 3' UTR, CDS. Generic UTR features are resolved using transcript-specific CDS boundaries and strand, while introns are derived from transcript exon structure. We benchmarked PeakLocus against BEDTools, UROPA, ChIPseeker, and HOMER using 466,526 evaluable RNA-associated peaks from 27 Drosophila, mouse, and human datasets and a balanced reference-derived benchmark of 30,000 fixed-width intervals. On real-world data, PeakLocus assigned a strict RNA-location category to 92.8% of evaluable intervals and showed 99.5% concordance with a direct BEDTools-derived overlap baseline among jointly annotated peaks. In the controlled benchmark, PeakLocus achieved 86.4% exact five-class recovery overall, with 99.9% recovery in mouse and 99.6% in human. Comparator differences were strongly influenced by native annotation ontology, including CDS-versus-exon resolution, intron representation, and non-RNA categories. PeakLocus provides a lightweight and interpretable framework for transcript-aware annotation of RNA-associated genomic intervals.

bioinformatics↗

Alternative 3' Polyadenylation Responses to Acute Ethanol Exposure Differ Between Drosophila Populations

Alternative polyadenylation is a pervasive post-transcriptional mechanism that generates mRNA isoforms with distinct 3 untranslated regions (3 UTRs), which can influence transcript stability, localization and translation. Ethanol is an environmental stressor for Drosophila melanogaster, and natural populations show distinct responses to ethanol exposure, suggesting that the genetic background can modulate phenotypic response. Yet, how the natural genetic variation modulates ethanol-responsive APA remains understudied. We profiled 3 end isoforms following acute ethanol exposure in three French (cosmopolitan) and three Zambian (ancestral range) D. melanogaster genotypes and identified numerous significant APA events across all genotypes. Ethanol-induced APA was widespread but highly genotype - and population - dependent: the French genotypes showed an enrichment of proximal shifts (3 UTR shortening), while Zambian genotypes were biased toward distal shifts (3 UTR lengthening). Most of the ethanol-responsive APA events were private to a single population, with relatively few genes exhibiting conserved directional changes across both backgrounds. We also classify genes showing opposite-direction shifts between populations, and others with opposite-direction shifts between various classes of APA. For two-site events, inter-poly(A) site distance did not predict response direction; however, spacing strongly predicted the magnitude of remodeling, with larger separations enabling greater absolute 3 UTR length changes. Our findings support a model in which ethanol-responsive 3 end regulation is a flexible genetically contingent, and that population-specific APA remodeling represent a plausible molecular substrate contributing to adaptation.

genomics↗

Rapid evolution and comparative analysis of piRNA clusters in D.simulans

Eukaryotic genomes are ubiquitously occupied by mobile genetic elements termed transposons, which are silenced via a specialized class of small RNA called piRNA. The small RNA is produced from the transposons themselves when they occupy specialized regions of the genome termed piRNA clusters. The formation of these specialized regions, or their evolution over time, is not well understood. Recent work has suggested that they are extremely variable even within a single species such as Drosophila melanogaster. We were interested in taking a comparative approach to piRNA cluster evolution to ask the question - what processes are unique to D. melanogaster and which are shared? Shared phenomena are more likely to be fundamental aspects of piRNA formation and evolution compared to those that are more labile. Using five high-quality long-read genome assemblies and five genotype-specific piRNA libraries, we approach this question from a population genetics standpoint. We annotate piRNA clusters, transposons, and structural variants in each of these five genomes. We found extensive variation in piRNA clusters across strains, with smaller piRNA clusters more likely to be limited to a single genotype. By and large, our results are consistent with a model of piRNA cluster evolution in which piRNA clusters are rapidly formed and lost, with a small subset increasing in frequency and length over time. However, we find that the TEs which nucleate the formation of small piRNA clusters are entirely distinct in D. simulans compared to D. melanogaster, and likely reflect its invasion history rather than any inherent property of the transposon to nucleate clusters. Therefore, while large common clusters can act as traps as has been posited for piRNA clusters, there are also numerous small clusters that are born and lost rapidly within a species.

evolutionary biology↗

Recent horizontal transfer of transposable elements in Drosophila

Transposable elements are small pieces of DNA which selfishly increase in copy number within genomes. Transposable elements can also move between species through unknown intermediaries in a process known as horizontal transfer, infecting novel genomes and increasing in copy number. In this manuscript we used almost 400 dipteran genomes to uncover 648 recent transposon invasions, mostly in Drosophila. We limited our results to transposons with 99% similarity to capture recent transfers. When our results overlapped with previous studies they were largely replicated. The majority of transfers occurred between closely related species, with the cosmopolitan melanogaster group showing the highest recent transfer activity. However, we documented 60 HT events spanning more than 30 million years of evolution. Gypsy and Mariner elements were involved in the most HT events. While the majority of elements were implicated in fewer than five transfers, we documented a single transposon with as many as with 16 recent transfers, many between different Drosophila groups. In addition, we found that while LTR elements engage in HT more frequently, DNA elements travel longer phylogenetic distances when engaging in HT. This potentially represents a different evolutionary strategy for exploiting naive genomes. Our phylogenetic framework advances the understanding of horizontal transfer dynamics at the species level within Drosophila.

evolutionary biology↗

The ongoing invasion of the endogenous retrovirus Kuruka in natural Drosophila melanogaster populations

Transposable elements are mobile DNA sequences capable of proliferating within host genomes, occasionally capable of crossing species boundaries via horizontal transfer (HT). Here, we report the discovery and characterization of Kuruka, a newly invading endogenous retrovirus in natural D. melanogaster populations. Kuruka encodes an envelope protein and belongs to the gypsy /gypsy superfamily. Analysis of over 1000 D. melanogaster genomes revealed that Kuruka first appeared in sub-Saharan Africa in 2010. By 2017-2019 Kuruka had spread to Asia, Europe and America in 2017-2019, and is still actively invading Europe and Oceania as of 2021. Phylogenomic analyses suggest that Kuruka entered in D. melanogaster via a recent HT from an Afrotropical Drosophila species, most likely D. erecta. This is the first case of a recent HT from an Afrotropical donor species to D. melanogaster. In D. erecta, Kuruka has a single genomic insertion, which is located within flamenco, a master regulator of TE activity. The presence of an active host defense (piRNAs) suggests that Kuruka is silenced in D. erecta. Our findings establish Kuruka as a valuable model for studying the early stages of TE invasions and the dynamics of genome defense in real time.

genomics↗

Tracking polygenic adaptation: phenotypic stasis after rapid adaptation in large populations of Drosophila

Most adaptive traits have a polygenic basis, and their evolution in response to environmental change results from the cumulative effect of many underlying loci. Theoretical studies predict two phases of phenotypic evolution: an initial directional phase, characterized by shifts in the mean of the trait towards a new optimum; and a subsequent stabilizing phase, in which the mean phenotype remains constant. However, there is limited empirical evidence to confirm these predictions. We exposed six replicate populations of Drosophila simulans, each with 100,000 individuals, to a new high-protein diet for 31 generations. Using time-series of high-order and molecular phenotypes, we characterized the phases of polygenic adaptation and inferred the transition between the directional and stabilizing selection phases empirically. The initial (directional) phase was characterized by a rapid phenotypic response, followed by a plateau after seven generations of adaptation, suggesting proximity to the new trait optimum (i.e. the stabilizing phase). The phenotypic responses were highly parallel among the replicate populations throughout the experiment. The contribution of pleiotropic loci to adaptive phenotypic evolution varied across the different phases of adaptation. Adaptation throughout the experiment was mainly facilitated by genes with low-to-intermediate pleiotropy, while highly pleiotropic genes played a significant role in the initial phase of adaptation. Parallel evolutionary responses across the replicate populations were also driven by genes with low-to-intermediate pleiotropy. Our findings support the predictions of theoretical models and provide empirical evidence for directional and stabilizing phases of polygenic adaptation.

evolutionary biology↗

The impact of insertion bias into piRNA clusters on the invasion of transposable elements

In our current understanding of transposable element (TE) invasions TEs move freely until they accidentally insert into a piRNA cluster. They are then silenced by the production of piRNA cognate to the TE. Under this model, one would expect that TEs might evolve to avoid piRNA clusters. Yet empirical observations show that some TEs, such as the P -element, insert into piRNA clusters preferentially. We were thus wondering if such a bias could be beneficial for the TE, for example by minimizing harm to the host while still being able to selfishly spread in populations. We decided to model insertion bias to determine if there was ever a situation in which insertion bias was beneficial to the TE. We performed extensive forward simulations of TE invasions with differing insertion biases into piRNA clusters. We found that insertion bias significantly altered the invasion dynamics of TEs, primarily by changing the copy number of the TE in individuals prior to silencing. Insertion into a piRNA cluster reduced the deleterious effects of TEs to the host population, but we found that TEs avoiding piRNA clusters out-compete TEs with a bias towards cluster insertions. Insertion bias was only beneficial to the TE when there was negative selection against TEs and a lack of recombination. Different TEs show different insertion biases into piRNA clusters suggesting they are an attribute of the TE not the host, yet scenarios in which this is beneficial to the TE are quite limited. This opens up an interesting area of future research into the dynamics of insertion bias during TE invasions. Significance StatementThis study challenges the pre-existing understanding of the TE dynamics by investigating the potential adaptive role of insertion bias into piRNA clusters. Using extensive forward simulations, we demonstrate that while insertion bias significantly alters TE invasion dynamics, it is generally not beneficial for the TEs spread in populations. Our results also show that transposable elements (TEs) that avoid piRNA clusters tend to do better than those that are more likely to preferencially insert into these clusters. This work provides novel insights into the complex dynamics between TEs and host genomes, showing the limited scenarios where the insertion bias could be advantageous to TEs. These results open new area for research into TE invasion dynamics and the evolution of host-TE interactions, further contributing to our understanding of genome evolution and stability.

evolutionary biology↗

Unveiling the complete invasion history of D. melanogaster: three horizontal transfers of transposable elements in the last 30 years

Transposable elements (TEs) are repetitive sequences capable of mobilizing within genomes, exerting significant influence on evolution throughout the tree of life. Using a novel approach that does not require prior knowledge about the sequence of repeats, we identified three novel TE invasions in D. melanogaster : MLE spread between 1990-2000, Souslik between 2009-2012, and Transib1 between 2013-2016. We recapitulate prior findings, revealing that a total of 11 TEs invaded D. melanogaster over the past two centuries. Leveraging data from over 1400 arthropod genomes, we provide evidence that the TE invasions were triggered by horizontal transfers, with D. simulans and species of the D. willistoni group acting as putative donors. Through analysis of[~] 600 short-read datasets spanning diverse geographic regions, we reveal the rapidity of TE invasions: Transib1 swiftly multiplied from three isolated epicenters in 2014 to all investigated populations within just two years. Our findings suggest that anthropogenic activities, facilitating habitat and population expansions of D. melanogaster, might have accelerated the rate of horizontal transposon transfer as well the spread of the TEs into the worldwide population. Given the significant impact of TEs in genomes and the potential involvement of humans in their dispersal, our research has crucial implications for both evolution and ecology.

genomics↗

Spoink, a LTR retrotransposon, invaded D. melanogaster populations in the 1990s

During the last few centuries D. melanogaster populations were invaded by several transposable elements, the most recent of which was thought to be the P-element between 1950 and 1980. Here we describe a novel TE, which we named Spoink, that has invaded D. melanogaster. It is a 5216nt LTR retrotransposon of the Ty3/gypsy superfamily. Relying on strains sampled at different times during the last century we show that Spoink invaded worldwide D. melanogaster populations after the P-element between 1983 and 1993. This invasion was likely triggered by a horizontal transfer from the D. willistoni group, much as the P-element. Spoink is probably silenced by the piRNA pathway in natural populations and about 1/3 of the examined strains have an insertion into a canonical piRNA cluster such as 42AB. Given the degree of genetic investigation of D. melanogaster it is surprising that Spoink was able to invade unnoticed.

evolutionary biology↗

Evolution of Plasticity in Response to Ethanol between Recently Separated Populations of D. melanogaster with Different Ecological Histories

The evolution of phenotype plasticity by genetic accommodation was theorized but has not been extensively demonstrated. Under this model of evolution when a population encounters a new environment there are widely variable responses amongst different genotypes, which are then pruned by selection into a single adaptive response. Because of the requirement to replicate genotypes, testing this predication requires inbred lines as well as populations that are both adapted and not adapted to a resource. We previously demonstrated that D. melanogaster adapted to ethanol through genetic accommodation using D. simulans as an ancestral proxy lineage. However, we wondered how generalizable these results were. Using a new population of D. melanogaster from France and an ancestral range population from Zambia we demonstrated here that the Zambian population is not adapted to ethanol and that the French population has evolved ethanol resistance through genetic accommodation. We also investigated alternative splicing in response to ethanol and find that gene expression and splicing appear to evolve independently of one another, and that the splicing response to ethanol is largely distinct between populations. Thus we have independently replicated evidence for evolution by genetic accommodation in D. melanogaster, suggesting that the evolution of plasticity may be an important contributor to the ability to exploit novel resources.

evolutionary biology↗

Sex-biased expression is associated with chromatin state in D. melanogaster and D. simulans

We propose a new model for the association of chromatin state and sex-bias in expression. We hypothesize enrichment of open chromatin in the sex where we see expression bias (OS) and closed chromatin in the opposite sex (CO). In this study of D. melanogaster and D. simulans head tissue, sex-bias in expression is associated with H3K4me3 (open mark) in males for male-biased genes and in females for female-biased genes in both species. Sex-bias in expression is also largely conserved in direction and magnitude between the two species on the X and autosomes. In male-biased orthologs, the sex-bias ratio is more divergent between species if both species have H3K27me2me3 marks in females compared to when either or neither species has H3K27me2me3 in females. H3K27me2me3 marks in females are associated with male-bias in expression on the autosomes in both species, but on the X only in D. melanogaster. In female-biased orthologs the relationship between the species for the sex-bias ratio is similar regardless of the H3K27me2me3 marks in males. Female-biased orthologs are more similar in the ratio of sex-bias than male-biased orthologs and there is an excess of male-bias in expression in orthologs that gain/lose sex-bias. There is an excess of male-bias in sex-limited expression in both species suggesting excess male-bias is due to rapid evolution between the species. The X chromosome has an enrichment in male-limited H3K4me3 in both species and an enrichment of sex-bias in expression compared to the autosomes.

evolutionary biology↗

Rapid evolutionary diversification of the flamenco locus in the D. simulans clade

Effective suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. In D. melanogaster, flamenco is a master suppressor of TEs, preventing their movement from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, that is metabolized into Piwi-interacting RNAs (piRNAs) that target active TEs via antisense complementarity. flamenco is thought to operate as a trap, owing to its high content of recent horizontally transferred TEs that are enriched in antisense orientation. Using newly-generated long read genome data, which is critical for accurate assembly of repetitive sequences, we find that flamenco has undergone radical transformations in sequence content and even copy number across simulans clade Drosophilid species. D. simulans flamenco has duplicated and diverged, and neither copy exhibits synteny with D. melanogaster beyond the core promoter. Moreover, flamenco organization is highly variable across D. simulans individuals. Next, we find that D. simulans and D. mauritiana flamenco display signatures of a dual-stranded cluster, with ping-pong signals in the testis and/or embryo. This is accompanied by increased copy numbers of germline TEs, consistent with these regions operating as functional dual stranded clusters. Overall, the physical and functional diversity of flamenco orthologs is testament to the extremely dynamic consequences of TE arms races on genome organization, not only amongst highly related species, but even amongst individuals.

evolutionary biology↗

Evolutionary dynamics of piRNA clusters in Drosophila

Small RNAs produced from transposable element (TE) rich sections of the genome, termed piRNA clusters, are a crucial component in the genomic defense against selfish DNA. In animals it is thought the invasion of a TE is stopped when a copy of the TE inserts into a piRNA cluster, triggering the production of cognate small RNAs that silence the TE. Despite this importance for TE control, little is known about the evolutionary dynamics of piRNA clusters, mostly because these repeat rich regions are difficult to assemble and compare. Here we establish a framework for studying the evolution of piRNA clusters quantitatively. Previously introduced quality metrics and a newly developed software for multiple alignments of repeat annotations (Manna) allow us to estimate the level of polymorphism segregating in piRNA clusters and the divergence among homologous piRNA clusters. By studying 20 conserved piRNA clusters in multiple assemblies of four Drosophila species we show that piRNA clusters are evolving rapidly. While 70-80% of the clusters are conserved within species, the clusters share almost no similarity between species as closely related as D. melanogaster and D. simulans. Furthermore, abundant insertions and deletions are segregating within the Drosophila species. We show that the evolution of clusters is mainly driven by large insertions of recently active TEs, and smaller deletions mostly in older TEs. The effect of these forces is so rapid that homologous clusters often do not contain insertions from the same TE families.x

evolutionary biology↗

The transposable elements of the Drosophila serrata reference panel

Transposable elements are an important element of the complex genomic ecosystem, proving to be both adaptive and deleterious - repressed by the piRNA system and fixed by selection. Transposable element insertion also appears to be bursty - either due to invasion of new transposable elements that are not yet repressed, de-repression due to instability of organismal defense systems, stress, or genetic variation in hosts. Here, we characterize the transposable element landscape in an important model Drosophila, D. serrata, and investigate variation in transposable element copy number between genotypes and in the population at large. We find that a subset of transposable elements are clearly related to elements annotated in D. melanogaster and D. simulans, suggesting they spread between species more recently than other transposable elements. We also find that transposable elements do proliferate in particular genotypes, and that often if an individual is host to a proliferating transposable element, it is host to more than one proliferating transposable element. In addition, if a transposable element is active in a genotype, it is often active in more than one genotype. This suggests that there is an interaction between the host and the transposable element, such as a permissive genetic background and the presence of potentially active transposable element copies. In natural populations an active transposable element and a permissive background would not be held in association as in inbred lines, suggesting the magnitude of the burst would be much lower. Yet many of the inbred lines have actively proliferating transposable elements suggesting this is an important mechanism by which transposable elements maintain themselves in populations.

genomics↗

Evolution of phenotypic plasticity in response to ethanol between sister species with different ecological histories (Drosophila melanogaster and D. simulans)

The contribution of phenotypic plasticity to adaptation is contentious, with contradictory empirical support for its role in evolution. Here I investigate the possibility that phenotype plasticity has contributed to adaptation to a novel resource. If phenotype plasticity contributes to adaptation, it is thought to evolve in a process termed genetic accommodation. Under this model, the initial response to the environment is widely variable due to cryptic genetic variation, which is then refined by selection to a single adaptive response. I examine the role of phenotypic plasticity in adaptation here by comparing two species of Drosophila that differ in their adaptation to ethanol (Drosophila melanogaster and D. simulans). Both species are human commensals with a recent cosmopolitan expansion, but only D. melanogaster is adapted to ethanol exposure. I measure phenotype plasticity in response to ethanol with gene expression and an approach that combines information about expression and alternative splicing. I find evidence for adaptation to ethanol through genetic accommodation, suggesting that the evolution of phenotype plasticity contributed to the ability of D. melanogaster to exploit a novel resource. I also find evidence that alternative splicing may be more important for the adaptive response to ethanol than overall changes in exon expression.

evolutionary biology↗

Quantitative variation and evolution of spatially explicit morphogen expression in Drosophila

Robustness in development allows for the accumulation of neutral genetically based variation in expression, and here will be termed genetic stochasticity . This largely neutral variation is potentially important for both evolution and complex disease phenotypes. However, it has generally only been investigated as variation exhibited in the response to large genetic perturbations. In addition, work on variation in gene expression has similarly generally been limited to being spatial, or quantitative, but because of technical restrictions not both. Here we bridge these gaps by investigating replicated quantitative spatial gene expression using rigorous statistical models, in different genotypes, sexes, and species (Drosophila melanogaster and D. simulans). Using this type of quantitative approach with developmental data allows for effective comparison among conditions, including health versus disease. We apply this approach to the morphogenetic furrow, a wave of differentiation that sweeps across the developing eye disc. Within the morphogenetic furrow, we focus on four conserved morphogens, hairy, atonal, hedgehog, and Delta. Hybridization chain reaction quantitatively measures spatial gene expression, co-staining for all four genes simultaneously and with minimal effort. We find considerable variation in the spatial expression pattern of these genes in the eye between species, genotypes, and sexes. We also find that there has been evolution of the regulatory relationship between these genes. Lastly, we show that the spatial interrelationships of these genes evolved between species in the morphogenetic furrow. This is essentially the first population genetics of development as we are able to evaluate wild type differences in spatial and quantitative gene expression at the level of genotype, species and sex.

developmental biology↗

Population genomics of Wolbachia and mtDNA in Drosophila simulans from California

Wolbachia pipientis is an intracellular endosymbiont in fecting many arthropods and filarial nematodes. Little is known about the short-term evolution of Wolbachia or its interaction with its host. Wolbachia is maternally inherited, resulting in co-inheritance of mitochondrial organelles such as mtDNA. Here I explore the short-term evolution of Wolbachia, and the relationship between Wolbachia and mtDNA, using a large inbred panel of Drosophila simulans infected with the Wolbachia strain wRi. I find reduced diversity relative to expectation in both Wolbachia and mtDNA, but only mtDNA shows evidence of a recent selective sweep or population bottleneck. I estimate Wolbachia and mtDNA titre in each genotype, and I find considerable variation in both phenotypes, despite low genetic diversity in Wolbachia and mtDNA. A phylogeny of Wolbachia and of mtDNA show that both trees are largely unresolved, suggesting a recent origin of the infection and a single origin. Using Wolbachia and mtDNA titre as a phenotype, we perform an association analysis with the nuclear genome and find several regions implicated in the phenotype, including one which contains four CAAX-box protein processing genes. CAAX-box protein processing can be an important part of host-pathogen interactions in other systems, suggesting interesting directions for future research.

evolutionary biology↗