Biology subjects

Tauber, E.

Publications and source records attributed to Tauber, E..

12 recordsLinked to original sources

bioRxiv2026

Synonymous codon usage is biased for and against m⁶A RRACH motifs in mammals

RNA methylation at N6-adenosine (m6A) predominantly occurs within RRACH motifs, yet the forces shaping these motifs in coding regions remain unclear. Here we show that the synonymous codon combinations able to form or disrupt RRACH sites are used non-randomly across mammals. Using 13,491 protein-coding genes from 261 species, we identified genes significantly enriched or depleted in RRACH motifs, a pattern consistent with gene-specific selection for or against m6A potential. Genes enriched in RRACH sites were linked to ubiquitin-like conjugation and cell cycle regulation, whereas transmembrane and HOX genes were RRACH-poor, likely reflecting sequence incompatibility with CpG dinucleotides. Cross-species comparison with Caenorhabditis elegans, which lacks mRNA m6A methylation, revealed reciprocal RRACH frequencies, as expected if these motifs are under selection in m6A-competent genomes but evolve without this constraint otherwise. At the codon level, specific amino acid pairs, particularly threonine-ending dyads, were biased toward RRACH-forming codons while others were depleted, indicating that synonymous codon choice is skewed for and against motif formation. RRACH motifs were also non-randomly distributed along coding sequences, depleted near start codons and enriched toward the 3' end, consistent with known m6A profiles. Finally, analysis of cancer mutations revealed tissue-specific gain and loss of RRACH sites, reflecting context-dependent remodeling of methylation potential. Together, these results show that synonymous codon usage is systematically biased for and against m6A RRACH motifs, pointing to an evolutionary coupling between the genetic code and the epitranscriptomic landscape.

genomics↗

bioRxiv2026

Natural Variation in Clock polyQ Length Is Associated with Circadian Function to Climatic Gradients in Drosophila melanogaster

Natural variation in circadian clock genes provides a powerful framework for understanding how organisms respond to environmental heterogeneity. The Clock (Clk) gene encodes a core transcriptional regulator of circadian rhythms and contains a polymorphic polyglutamine (polyQ) tract whose evolutionary significance remains unclear. Here, we integrate population genomic, behavioral, and molecular analyses to investigate the functional and geographic patterns of Clk polyQ variation in Drosophila melanogaster. Using data from 127 European populations, we identify 11 Clk polyQ alleles and find that their frequencies are geographically structured, most consistently along an east-west gradient: the Q25 and Q27 alleles show robust clines in longitude and in a bioclimatic axis of continentality, whereas latitudinal and altitudinal trends are weaker. Behavioral assays of near-isogenic lines revealed that polyQ length modulates circadian function under thermal challenge: most alleles maintained stable free-running periods across temperatures, whereas the intermediate-length Q25 allele showed the strongest, though modest, temperature sensitivity. Circadian phase showed pronounced allele-specific sensitivity to elevated temperature in laboratory assays, although phase variation did not display a consistent relationship with geographic variables. At the molecular level, luciferase reporter assays showed that longer polyQ alleles exhibited higher transcriptional activity, linking polyQ length to CLK-mediated gene expression. Together, these results demonstrate that natural variation in Clk polyQ length has measurable functional consequences for circadian regulation and is geographically structured in patterns consistent with underlying climatic variation, highlighting the potential for low-complexity regions to modulate clock function in a context-dependent manner across environmental gradients.

evolutionary biology↗

bioRxiv2025

Mapping the Regulatory Architecture of Circadian Clock Adaptation: A Genome-Wide eQTL Analysis in Drosophila melanogaster

The circadian clock system enables organisms to synchronize internal daily rhythms with environmental cues, critically impacting survival and fitness. While the molecular architecture of this system in Drosophila melanogaster is well-characterized through transcription-translation negative feedback loops involving ten core clock genes, regulatory genetic variants affecting their expression remain largely unexplored. This study leveraged natural variation in clock gene expression to identify expression quantitative trait loci (eQTLs) through genome-wide association mapping. We utilized the Drosophila Genomic Reference Panel (DGRP), consisting of 205 fully sequenced inbred lines, and measured relative expression levels of all core clock genes in 120 lines via qPCR at a single time point (two hours after light onset). GWAS analysis identified 137 significant SNPs (p < 10-5) associated with expression variation across the clock genes. Expression levels showed substantial natural variation, with pdp1{varepsilon} exhibiting the highest variability (89-fold difference between extreme lines) and cyc the lowest (11.3-fold). Interestingly, only three significant SNPs were located within clock genes themselves (all in Clk), while the majority represented trans-eQTLs in genes with diverse molecular functions. Notable candidates include transcription factors (e.g. Abd-B, tai, E5), RNA-binding proteins (PUM, Bru-3, Mbl), and long non-coding and antisense RNAs. Variants were also found in Mad and gbb, genes implicated in the BMP signaling pathway, which has previously been linked to circadian regulation. This comprehensive eQTL map provides new insights into the regulatory architecture of the circadian clock system and potential mechanisms of evolutionary adaptation to environmental timing cues.

genomics↗

bioRxiv2025

The Evolutionary Flexibility of the Drosophila Circadian Clock: Network Constraints or Adaptive Freedom?

The study of network evolution is critical to understanding how complex biological processes arise and adapt over time. Protein networks, composed of interacting components, can exhibit varying degrees of conservation and flexibility, enabling organisms to fine-tune their responses to environmental changes. Using the circadian clock system in Drosophila as a case study, we explore how such networks evolve. We leverage the recently published 101 Drosophilidae genome project to analyze the evolution and co-evolution of 11 core clock proteins across 65 species spanning about 60 million years of evolution. A sliding window analysis of coding regions reveals substantial heterogeneity in nucleotide divergence, with Clk and per exhibiting high divergence, whereas Pdp1 and sgg show virtually no evolutionary change. Additionally, we assessed interdependent amino acid evolution across different proteins, identifying 67 co-evolving site pairs, primarily between CLK-PER, CLK-CWO, and SGG-PER. Using codon-based models of evolution we found four genes (cwo, jet, per, and sgg) showing evidence of positive selection. Since several clock proteins are pleiotropic, we tested whether their multifunctionality influences their evolutionary constraints. Using alternative approaches to assess pleiotropy, we found no significant correlation between pleiotropy and the non-synonymous substitution rate (Ka) in 440 Drosophila proteins, including circadian clock ones. Overall, our findings suggest that the circadian clock network does not impose strong constraints on the evolution of its components. This flexibility may facilitate species-specific adaptation of the clock and allow the pleiotropic functions of clock proteins.

evolutionary biology↗

bioRxiv2022

Transcriptional response of circadian clock genes to an 'artificial light at night' pulse in the cricket Gryllus bimaculatus

Light is the major signal entraining the circadian clock that regulates physiological and behavioral rhythms in most organisms, including insects. Artificial Light at Night (ALAN) disrupts the natural light-dark cycle and negatively impacts animals at various levels. We simulated ALAN using dim light stimuli and tested their impact on gene expression in the cricket Gryllus bimaculatus, a model of insect physiology and chronobiology. At night, adult LD crickets were exposed for 30 minutes to a light pulse of 2-40 lx. The relative expression of five circadian clock associated genes was compared using qPCR. A dim ALAN pulse elicited tissue-dependent differential expression in some of these genes. The strongest effect was observed in the brain and in the optic lobe, the crickets circadian pacemaker. Expression of opsin-Long Wave (opLW) was upregulated, as well as cryptochrome1-2 (cry), and period (per). Our findings demonstrate that even a dim ALAN exposure may affect insects at the molecular level, underscoring the detrimental impact of ALAN on the circadian clock system.

animal behavior and cognition↗

bioRxiv2021

Metagenomic analysis reveals the signature of gut microbiota associated with human chronotypes

Patterns of diurnal activity differ substantially between individuals, with early risers and late sleepers being examples of opposite chronotypes. Growing evidence suggests that the late chronotype significantly impacts the risk of developing mood disorders, obesity, diabetes, and other chronic diseases. Despite the vast potential of utilizing chronotype information for precision medicine, those factors that shape chronotypes remain poorly understood. Here, we assessed whether the various chronotypes are associated with different gut microbiome compositions. Using metagenomic sequencing analysis, we established a distinct signature associated with chronotype based on two bacterial genera, Alistipes (elevated in "larks") and Lachnospira (elevated in "owls"). We identified three metabolic pathways associated with the early chronotype, and linked distinct dietary patterns with different chronotypes. Our work demonstrates an association between the gut microbiome and chronotype and may represent the first step towards developing dietary interventions aimed at ameliorating the deleterious health correlates of the late chronotype.

genomics↗

bioRxiv2021

Drosophila Evolution over Space and Time (DEST) - A New Population Genomics Resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last 20 years. A major challenge is the integration of these disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution and population structure of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 population samples from over 100 locations in >20 countries on four continents based on a combination of 121 unpublished and 150 previously published genomic datasets. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.

genomics↗

bioRxiv2018

Photoperiod-dependent expression of MicroRNA in Drosophila

Like many other insects in temperate regions, Drosophila melanogaster exploits the photoperiod shortening that occurs during the autumn as an important cue to trigger a seasonal response. Flies survives the winter by entering a state of reproductive arrest (diapause), which drives relocation of resources from reproduction to survival. Here, we profiled the expression of microRNA (miRNA) in long and short photoperiods and identified seven differentially expressed miRNAs (dme-mir-2b, dme-mir-11, dme-mir-34, dme-mir-274, dme-mir-184, dme-mir-184* and dme-mir-285). Misexpression of dme-mir-2b, dme-mir-184 and dme-mir-274 in pigment-dispersing factor-expressing neurons largely disrupted the normal photoperiodic response, suggesting that these miRNAs play functional roles in photoperiodic timing. We also analyzed the targets of photoperiodic miRNA by both computational predication and by Argonaute-1- mediated immunoprecipitation of long- and short-day RNA samples. Together with global transcriptome profiling, our results expand existing data on other Drosophila species, identifying genes and pathways that are differentially regulated in different photoperiods and reproductive status. Our data suggest that post-transcriptional regulation by miRNA is an important facet of photoperiodic timing.

genomics↗

bioRxiv2018

Genome-wide disruption of DNA methylation by 5-aza-2’-deoxycytidine in the parasitioid wasp Nasonia vitripennis

DNA methylation of cytosine residues across the genome influences how genes and phenotypes are regulated in a wide range of organisms. As such, understanding the role of DNA methylation and other epigenetic mechanisms has become very much a part of mapping genotype to phenotype, a major question in evolutionary biology. Ideally, we would like to manipulate DNA methylation patterns on a genome-wide scale, to help us to elucidate the role that epigenetic modifications play in phenotypic expression. Recently, the demethylating agent 5-aza-2-deoxycytidine (5-aza-dC; commonly used in the epigenetic treatment of certain cancers), has been deployed to explore the epigenetic regulation of a number of traits of interest to evolutionary ecologists, including facultative sex allocation in the parasitoid wasp Nasonia vitripennis. In a recent study, we showed that treatment with 5-aza-dC did not ablate the facultative sex allocation response in Nasonia, but shifted the patterns of sex allocation in a way predicted by genomic conflict theory. This was the first (albeit indirect) experimental evidence for genomic conflict over sex allocation facilitated by DNA methylation. However, that work lacked direct evidence of the effects of 5-aza-dC on DNA methylation, and indeed the effect of the chemical has since been questioned in Nasonia. Here, using whole-genome bisulphite sequencing of more than 4 million CpGs, across more than 11,000 genes, we demonstrate unequivocally that 5-aza-dC disrupts methylation on a large scale across the Nasonia vitripennis genome. We show that the disruption can lead to both hypo- and hyper-methylation, may vary across tissues and time of sampling, and that the effects of 5-aza-dC are context- and sequence specific. We conclude that 5-aza-dC does indeed have the potential to be repurposed as a tool for studying the role of DNA methylation in evolutionary ecology, whilst many details of its action remain to be discovered. Author SummaryShedding light on the mechanistic basis of phenotypes is a major aim in the field of evolutionary biology. If we understand how phenotypes are controlled at the molecular level, we can begin to understand how evolution has shaped that phenotype and conversely, how genetic architecture may constrain trait evolution. Epigenetic markers (such as DNA methylation) also influence phenotypic expression by regulating how and when genes are expressed. Recently, 5-aza-2-deoxycytidine (5-aza-dC), a hypomethylating agent used in the treatment of certain cancers, has been used to explore the epigenetic regulation of traits of interest to evolutionary ecologists. Previously, we used 5-aza-dC to validate a role for DNA methylation in facultative sex allocation behaviour in the parasitoid wasp Nasonia vitripennis. However, the direct effects of the chemical were not examined at that point and its efficacy in insects was questioned. Here, we demonstrate that 5-aza-dC disrupts DNA methylation on a genome-wide scale in a context- and sequence-specific manner and results in both hypo- and hyper-methylation. Our work demonstrates that 5-aza-dC has the potential to be repurposed as a tool for studying the role of DNA methylation in phenotypic expression.

evolutionary biology↗

bioRxiv2018

The genetic basis of diurnal preference in Drosophila melanogaster

Most animals restrict their activity to a specific part of the day, being diurnal, nocturnal or crepuscular. The genetic basis underlying diurnal preference is largely unknown. Under laboratory conditions, Drosophila melanogaster is crepuscular, showing a bi-modal activity profile. However, a survey of strains derived from wild populations indicated that high variability among individuals exists, with diurnal and nocturnal flies being observed. Using a highly diverse population, we have carried out an artificial selection experiment, selecting flies with extreme diurnal or nocturnal preference. After 10 generations, we obtained highly diurnal and nocturnal strains. We used whole-genome expression analysis to identify differentially expressed genes in diurnal, nocturnal and crepuscular (control) flies. Other than one circadian clock gene (pdp1), most differentially expressed genes were associated with either clock output (pdf, to) or input (Rh3, Rh2, msn). This finding was congruent with behavioural experiments indicating that both light masking and the circadian pacemaker are involved in driving nocturnality. The diurnal and nocturnal selection strains provide us with a unique opportunity to understand the genetic architecture of diurnal preference.

evolutionary biology↗

bioRxiv2018

Genomic analysis of European Drosophila melanogaster populations on a dense spatial scale reveals longitudinal population structure and continent-wide selection

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatio-temporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterise variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.

evolutionary biology↗

bioRxiv2017

Mapping Quantitative Trait Loci Underlying Circadian Light Sensitivity In Drosophila

Despite the significant advance in our understanding of the molecular basis of light entrainment of the circadian clock in Drosophila, the underlying genetic architecture is still largely unknown. The aim of this study was to identify loci associated with variation in circadian photosensitivity, which are important for the evolution of this trait. We have used complementary approaches that combined quantitative trait loci (QTL) mapping, complementation testing and transcriptome profiling to dissect this variation.\n\nWe identified a major QTL on chromosome 2, which was subsequently fine-mapped using deficiency complementation mapping into two smaller regions spanning 139 genes, some of which are known to be involved in functions which have been previously implicated in light entrainment. Two genes implicated with the clock and located within that interval, timeless and cycle, failed to complement the QTL, indicating that alleles of these genes contribute to the variation in light response. Specifically, we find that the timeless s/ls polymorphism that has been previously shown to constitute a latitudinal cline in Europe, is also segregating in our recombinant inbred lines, and is contributing to the phenotypic variation in light sensitivity.\n\nWe have also profiled gene expression in two recombinant inbred strains that differ significantly in their photosensitivity, and identified a total of 368 transcripts that showed differential expression (FDR < 0.1). Out of 131 transcripts that showed a significant RIL by treatment interaction (i.e. putative expression QTL), four are located within QTL2

genetics↗