Biology subjects

Brown, A.

Publications and source records attributed to Brown, A..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Mineral Phase Changes During Intervertebral Disc Degeneration

Intervertebral disc disease is a common cause of pain and neurological deficits and is known to be associated with degeneration and calcification. Here we analysed samples of herniated disc material and compared it to material taken from non-herniated discs following surgical treatment in dogs. Our clinical approach to these cases allows collection of samples providing a unique opportunity for a case-controlled study such as this, an opportunity which is not available to the human neurosurgeon. We analysed all samples using Fourier transform infrared (FTIR) spectroscopy, as well as a proportion with X-ray diffraction (XRD) and transmission electron microscopy (TEM). FTIR spectra of the majority of herniated samples were consistent with the presence of crystalline hydroxyapatite, whereas most of the non-herniated discs showed spectra consistent with amorphous phosphate material. XRD analysis and TEM confirmed these findings and identified the amorphous material as amorphous calcium phosphate nanoparticle clusters of [~] 20 nm diameter and the crystalline hydroxyapatite material as needles up to 100 nm in length. The differences between the herniated and non-herniated discs indicate that the degenerative process involves a conversion of amorphous calcium phosphate into crystalline hydroxyapatite which precedes and may predispose the disc to herniate.

neuroscience↗

bioRxiv2024

Reproductive output of old polygynous males is limited by seminal fluid, not sperm number

Advancing male age can lead to reproductive senescence, which in males is thought to be largely driven by declines in the numbers of sperm transferred by old males. This decline is predicted to be particularly pronounced in polygynous species, where males become sperm limited over a mating sequence. However, males also transfer seminal fluid to females, and little is known about the contribution of seminal fluid to constrain the reproductive output of old, multiply-mating males. Using Drosophila melanogaster, we investigated whether age-related variation in male reproductive output is driven by differential limitation of sperm or seminal fluid, over a series of experimental matings. Consistent with reproductive senescence, old males produced fewer offspring than young males. However, this pattern was not driven by sperm limitation, with old males having more sperm and transferring similar numbers of sperm to a female, compared to young males. Yet surprisingly, females stored fewer sperm when mated to old than young males. Notably, females mated to old multiply-mating males produced more offspring when supplemented with seminal fluid, suggesting that fertility of old males over successive matings was limited by seminal fluid availability. Generally, our study indicates that germline maintenance might be prioritised over somatic maintenance as hypothesized by the disposable soma theory of ageing, and that seminal fluid senescence is a key contributor of reproductive decline with age. While other factors such as differential sperm viability and female post-mating responses could have also influenced our results, our study highlights the under-appreciated role of seminal fluid in mediating male reproductive senescence in polygynous species. Significance statementA key assumption in ageing research is that old males are less fertile than young males, and that this reduced fertility is partly driven by old males producing fewer sperm. However, senescence in male fertility can be caused via other ejaculate-mediated pathways, which we investigate using fruit flies. Contrary to expectations, we reveal that senescence in male fertility is not because of declines in male sperm reserves, but is instead due to age-related changes in seminal fluid and differences in female sperm storage with male age. These declines in the reproductive output of old, multiply-mating males are alleviated by supplementing females with "extra" seminal fluid. Our study demonstrates that male reproductive senescence is reversible, highlighting the underappreciated role of seminal fluid in modulating senescence in polygynous species. These results have potential for improving animal fertility and our understanding of sexual selection.

evolutionary biology↗

bioRxiv2024

Castanet: a pipeline for rapid analysis of targeted multi-pathogen genomic data

MotivationTarget enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present the Castanet pipeline: an analysis pipeline for end-to-end processing and consensus sequence generation for use with multi-pathogen enrichment sequencing data. Castanet is designed to work with short-read data produced by existing targeted enrichment strategies, but can be readily deployed on any BAM file generated by another methodology. It is packaged with usability features, including graphical interface and installer script. ResultsIn addition to genome reconstruction, Castanet reports method-specific metrics that enable quantification of capture efficiency, estimation of pathogen load, differentiation of low-level positives from contamination, and assessment of sequencing quality. Castanet can be used as a traditional end-to-end pipeline for consensus generation, but its strength lies in the ability to process a flexible, pre-defined set of pathogens of interest directly from multi-pathogen enrichment experiments. In our tests, Castanet consensus sequences were accurate reconstructions of reference sequences, including in instances where multiple strains of the same pathogen were present. Castanet performs effectively on standard laptop computers and can process the entire output of a 96-sample enrichment sequencing run (50M reads) using a single batch process command, in < 2 h. Availability and ImplementationSource code freely available under GPL-3 license at https://github.com/MultipathogenGenomics/castanet, implemented in Python 3.10 and supported in Ubuntu Linux 22.04 and other Bash-like environments. The data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB77004.

bioinformatics↗

bioRxiv2024

Chemical mate choice copying in Drosophila melanogaster

Mate choice is a critical decision especially for females that requires time and energy to assess potential partners genetic quality. Consequently, in many species, females have evolved the ability to utilize social information by copying the mate choices of others, usually based on visual cues. However, many species, especially invertebrates, primarily rely on chemical not visual cues. Using chemical rather than visual cues provides several advantages such as not requiring active observation of copulations. Despite of that, empirical evidence for the existence of chemical mate choice copying is scarce. Using Drosophila melanogaster, we provide the first demonstration of chemical mate choice copying. Females exposed to a recently mated select the same male genotype as the teacher female mated with at a higher frequency than expected by chance. Chemical mate choice copying requires sensing both male and female cues, which might indicate that other females have chosen that male genotype. Our work suggests that females, in the presence of mated females, increase choosiness at the virgin stage, elevating sexual selection on male traits. This study provides novel evidence that exploiting social information is more prevalent in flies than previously assumed.

animal behavior and cognition↗

bioRxiv2024

Stress contingent changes in Hog1 pathway architecture and regulation in Candida albicans

The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in Candida albicans. Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses. Functioning upstream of the Ssk2 MAPKKK is a two-component related signal transduction system comprising three sensor histidine kinases, a phosphotransfer protein Ypd1, and a response regulator Ssk1. Here, we report that Ssk1 is a master regulator of the Hog1 SAPK that promotes stress resistance and Hog1 phosphorylation in response to diverse stresses, except high osmotic stress. Notably, we find Ssk1 regulates Hog1 in a two-component independent manner by functioning as a scaffolding protein to promote interactions between the Ssk2 and Pbs2 kinases. We propose this scaffolding function is important to maintain a basal level of Hog1 phosphorylation which is necessary for oxidative stress, but not osmotic stress, mediated Hog1 activation. We find that osmotic stress triggers robust Pbs2 phosphorylation which drives its dissociation from Ssk2. In contrast, Pbs2 is not robustly phosphorylated following oxidative stress and the Ssk1-mediated Ssk2-Pbs2 interaction remains intact. Instead, oxidative stress-stimulated increases in phosphorylated Hog1 is dependent on the inhibition of protein tyrosine phosphatases that negatively regulate Hog1 coupled with the Ssk1-mediated promotion of basal Hog1 activity. Furthermore, we find that inhibition of protein tyrosine phosphatases is linked to the hydrogen peroxide induced oxidation of these negative regulators in a mechanism that is dependent thioredoxin. Taken together these data reveal stress contingent changes in Hog1 pathway architecture and regulation and uncover a novel mode of action of the Ssk1 response regulator in SAPK regulation. Author summaryAs a core stress regulator, the Hog1 stress-activated protein kinase (SAPK), is a key virulence determinant in many fungal pathogens. Despite this, little is known regarding the mechanisms by which different stresses trigger the phosphorylation and activation of Hog1. Here we present three novel findings regarding Hog1 regulation in the human fungal pathogen C. albicans. Firstly, we find that the response regulator protein, Ssk1, is a master regulator of Hog1 that forms a scaffold for the upstream Hog1-activating kinases, Ssk2 and Pbs2. Secondly, this scaffolding role maintains a basal level of Hog1 phosphorylation, which is important for responses to stresses, such as oxidative stress, that do not stimulate activation of the upstream Ssk2 and Pbs2 kinases. Instead, oxidative stress induced Hog1 phosphorylation is mediated through the oxidation and inactivation of protein tyrosine phosphatases that negatively regulate Hog1. Finally, we show that high osmotic stress induces the robust phosphorylation and activation of the upstream kinase Pbs2, which drives its dissociation from the Ssk1-mediated scaffold. These new insights into the regulation of the C. albicans Hog1 SAPK pathway offer new strategies to therapeutically target this core virulence determinant.

microbiology↗

bioRxiv2024

Heterogeneous brain region-specific responses to astrocytic mitochondrial DNA damage in mice

Astrocytes use Ca2+ signals to regulate multiple aspects of normal and pathological brain function. Astrocytes display context-specific diversity in their functions, and in their response to noxious stimuli between brain regions. Indeed, astrocytic mitochondria have emerged as key players in governing astrocytic functional heterogeneity, given their ability to dynamically adapt their morphology to regional demands on their ATP generation and Ca2+ buffering functions. Although there is reciprocal regulation between mitochondrial dynamics and mitochondrial Ca2+ signaling in astrocytes, the extent of this regulation into the rich diversity of astrocytes in different brain regions remains largely unexplored. Brain-wide, experimentally induced mitochondrial DNA (mtDNA) loss in astrocytes showed that mtDNA integrity is critical for proper astrocyte function, however, few insights into possible diverse responses to this noxious stimulus from astrocytes in different brain areas were reported in these experiments. To selectively damage mtDNA in astrocytes in a brain-region-specific manner, we developed a novel adeno-associated virus (AAV)-based tool, Mito-PstI, which expresses the restriction enzyme PstI, specifically in astrocytic mitochondria. Here, we applied Mito-PstI to two distinct brain regions, the dorsolateral striatum, and the hippocampal dentate gyrus, and we show that Mito-PstI can induce astrocytic mtDNA loss in vivo, but with remarkable brain-region-dependent differences on mitochondrial dynamics, spontaneous Ca2+ fluxes and astrocytic as well as microglial reactivity. Thus, AAV-Mito-PstI is a novel tool to explore the relationship between astrocytic mitochondrial network dynamics and astrocytic mitochondrial Ca2+ signaling in a brain-region-selective manner.

neuroscience↗

bioRxiv2024

Single-cell transcriptional and epigenetic mapping reveals cellular and molecular mechanisms driving non-ischemic cardiac fibrosis

Cardiac fibrosis is a major cause of cardiac dysfunction. Recently, single-cell genomic approaches have revealed in unprecedented resolution the orchestrated cellular responses driving cardiac fibrosis. Yet, the fibrosis-causing phenotypes that emerge in the heart following non-ischemic cardiac stress, and the transcriptional circuits that govern cell identity and drive fibrosis, are not well understood. Applying a paired multiomic approach, we reveal key transcriptional circuits, in mouse and human hearts, which are associated with fibrosis development following non-ischemic cardiac insults, independent of disease model, species or biological sex. Strikingly, we find the key regulatory events driving fibrosis are reversible at the single-cell transcriptional and epigenomic level, further pointing to key factors regulating fibrosis development and resolution. The transcriptional regulators identified in this study represent promising targets to ameliorate the development of fibrosis in the context of chronic stressors such as aging and hypertension.

cell biology↗

bioRxiv2024

Molecular response to multiple trace-element contamination of the European sardine

In marine ecosystems, the presence of trace elements resulting from anthropogenic activities has raised concerns regarding their potential effects on marine organisms. This study delves into the intricate relationship between trace element contamination and the physiological responses of a key marine species in the Mediterranean Sea: the European sardine. Since 2008, this species has been experiencing a significant crisis in the region, prompting numerous studies to investigate the potential factors behind the dramatic decline in sardines size, age, and body condition. However, thorough information on chemical contamination by trace elements and its physiological impact on this species was lacking. We found evidence for the accumulation of multiple elements in sardines, with a light East-West contamination gradient within the Gulf of Lions. While macro-physiological parameters (i.e. body condition) were not affected by contamination, pathways involved in cellular organization and response to stress were clearly upregulated, particularly in the liver, but also in muscle. In addition, a global upregulation in processes linked to the immune system, lipid homeostasis and oxidative stress was recorded in the liver. The associated energetic cost may add a substantial burden to sardines that already face multi-factorial constraints. This study also allows to pinpoint biomarkers of exposure and effects that may be important for monitoring Mediterranean sardines health. The results of this study and particularly the complex changes in protein expression demonstrate the need for future studies to test the concomitant effects of multiple stressors acting simultaneously, including large scale contamination.

physiology↗

bioRxiv2024

ROS responsive Aux/IAA multimerization modulates auxin responses

Reactive oxygen species (ROS) function as key signals in plants to enable adaptation to environmental stresses. Plant roots respond to transient water stress by temporarily ceasing branching using the acclimative response xerobranching1. In this study, we report that a rapid ROS burst regulates Xerobranching by inducing multimerization of auxin repressor protein IAA3/SHY2. Mutations in specific cysteine residues in IAA3/SHY2 disrupt redox-mediated multimerization and interaction with co-repressor TPL, but not with auxin response partner ARF7 and auxin receptor TIR1. ROS-mediated oligomerization of IAA3/SHY2 is required for efficient ARF mediated target gene repression during Xerobranching and lateral root emergence. We demonstrate that AUX/IAA proteins vary in their redox mediated multimerization, revealing a new auxin response regulatory mechanism that directly connects ROS sensing to auxin signalling. Our study reveals how ROS, auxin and water stress intersect to shape acclimative responses in plant roots and maintain their phenotypic plasticity.

plant biology↗

bioRxiv2024

Expanding the RNA polymerase biocatalyst solution space for mRNA manufacture

All mRNA products are currently manufactured in in vitro transcription (IVT) reactions that utilize single-subunit RNA polymerase (RNAP) biocatalysts. Although it is known that discrete polymerases exhibit highly variable bioproduction phenotypes, including different relative processivity rates and impurity generation profiles, only a handful of enzymes are generally available for mRNA biosynthesis. This limited RNAP toolbox restricts strategies to design and troubleshoot new mRNA manufacturing processes, which is particularly undesirable given the continuing diversification of mRNA product lines towards larger and more complex molecules. Herein, we describe development of a high-throughput RNAP screening platform, comprising complementary in silico and in vitro testing modules, that enables functional characterisation of large enzyme libraries. Utilizing this system, we identified eight novel sequence-diverse RNAPs, with associated active cognate promoters, and subsequently validated their performance as recombinant enzymes in IVT-based mRNA production processes. By increasing the number of available characterized functional RNAPs by > 130% and providing a platform to rapidly identify further potentially useful enzymes, this work significantly expands the RNAP biocatalyst solution space for mRNA manufacture, thereby enhancing capability to achieve application and molecule-specific optimisation of product yield and quality.

bioengineering↗

bioRxiv2024

Genome-wide patterns of non-coding sequence variation in the major fungal pathogen Aspergillus fumigatus

A. fumigatus is a deadly fungal pathogen, responsible for >400,000 infections/year and high mortality rates. A. fumigatus strains exhibit variation in infection-relevant traits, including in their virulence. However, most A. fumigatus protein-coding genes, including those that modulate its virulence, are shared between A. fumigatus strains and closely related non-pathogenic relatives. We hypothesized that A. fumigatus genes exhibit substantial genetic variation in the non-coding regions immediately upstream to the start codons of genes, which could reflect differences in gene regulation between strains. To begin testing this hypothesis, we identified 5,812 single-copy orthologs across the genomes of 263 A. fumigatus strains. A. fumigatus non-coding regions showed higher levels of sequence variation compared to their corresponding protein-coding regions. Specifically, we found that 1,274 non-coding regions exhibited <75% nucleotide sequence similarity (compared to 928 protein-coding regions) and 3,721 non-coding regions exhibited between 75% and 99% similarity (compared to 2,482 protein-coding regions) across strains. Only 817 non-coding regions exhibited [≥]99% sequence similarity compared to 2,402 protein-coding regions. By examining 2,482 genes whose protein-coding sequence identity scores ranged between 75% and 99%, we identified 478 total genes with signatures of positive selection only in their non-coding regions and 65 total genes with signatures only in their protein-coding regions. 28 of the 478 non-coding regions and 5 of the 65 protein-coding regions under selection are associated with genes known to modulate A. fumigatus virulence. Non-coding region variation between A. fumigatus strains included single nucleotide polymorphisms and insertions or deletions of at least a few nucleotides. These results show that non-coding regions of A. fumigatus genes harbor greater sequence variation than protein-coding regions, raising the hypothesis that this variation may contribute to A. fumigatus phenotypic heterogeneity.

evolutionary biology↗

bioRxiv2023

Transcriptional and Cellular Response of hiPSC-derived Microglia-Neural Progenitor Co-Cultures Exposed to IL-6

Elevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but the mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool to study the effects of IL-6 on features relevant for human neurodevelopment in vitro. We previously reported that hiPSC-derived microglia-like cells (MGLs) respond to IL-6, but neural progenitor cells (NPCs) in monoculture do not. Therefore, we investigated whether co-culturing hiPSC-derived MGLs with NPCs would trigger a cellular response to IL-6 stimulation via secreted factors from the MGLs. Using N=4 donor lines without psychiatric diagnosis, we first confirmed that NPCs can respond to IL-6 through trans-signalling when recombinant IL-6Ra is present, and that this response is dose-dependent. MGLs secreted soluble IL-6R, but at lower levels than found in vivo and below that needed to activate trans-signalling in NPCs. Whilst transcriptomic and secretome analysis confirmed that MGLs undergo substantial transcriptomic changes after IL-6 exposure and subsequently secrete a cytokine milieu, NPCs in co-culture with MGLs exhibited a minimal transcriptional response. Furthermore, there were no significant cell fate-acquisition changes when differentiated into post-mitotic cultures, nor alterations in synaptic densities in mature neurons. These findings highlight the need to investigate if trans-IL-6 signalling to NPCs is a relevant disease mechanism linking prenatal IL-6 exposure to increased risk for psychiatric disorders. Moreover, our findings underscore the importance of establishing more complex in vitro human models with diverse cell types, which may show cell-specific responses to microglia-released cytokines to fully understand how IL-6 exposure may influence human neurodevelopment.

neuroscience↗

bioRxiv2023

Characterization of the Pristionchus pacificus epigenetic toolkit reveals the evolutionary loss of the histone methyltransferase complex PRC2

Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation - or lack thereof - of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with C. elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to enable reverse-genetic experiments related to plasticity, and in doing so have described the first loss of PRC2 in a multicellular organism.

genetics↗

bioRxiv2023

Gray matter volume in women with the BRCA mutation with and without ovarian removal

ObjectiveOvarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimers disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counselled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM and this is in women without the BRCAm showing cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and BSO noted changes in cognition. MethodsThe present study looked at whole-brain changes in gray matter volume using high-resolution, quantitative MRI in women with BRCAm and intact ovaries (BRCA-preBSO) and after surgery with (BSO+ERT) and without (BSO) post-surgical estradiol hormone replacement therapy compared with agematched women (AMC) with their ovaries. ResultsThe BRCA-preBSO and BSO groups showed significant gray matter loss in left medial temporal and frontal lobe structures. BSO+ERT exhibited few areas of gray matter reductions compared to AMC. Novel to this study, we also observed that all three BRCAm groups exhibited gray matter increases compared with AMC, suggesting continued plasticity. ConclusionsThe present study provides evidence, through gray matter volume reductions, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, post-surgical ERT seems to ameliorate gray matter losses.

neuroscience↗

bioRxiv2023

The landscape of genomic structural variation in Indigenous Australians

Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference databases. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here, we apply population-scale whole genome long-read sequencing to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large indels (20-49bp; n=136,797) and structural variants (SVs; [≥]50bp; n=159,912), the majority of which are composed of tandem repeat or interspersed mobile element sequences (90%) and have not been previously annotated (73%). A large fraction of SVs appear to be exclusive to Indigenous Australians (>30%) and the majority of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short-tandem repeats (STRs) throughout the genome to characterise allelic diversity at 50 known disease loci, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among STR sequences. Our study sheds new light on the dimensions, diversity and evolutionary trajectories of genomic structural variation within and beyond Australia.

genomics↗

bioRxiv2023

Early Neolithic forest farming at Seven Springs, Martlesham, Suffolk from sedaDNA and pollen

The importance of small wetlands and springs to Mesolithic cultures is well established. However, few studies have focused on their significance and use by Early Neolithic agro-pastoralists. Here we present a multiproxy palaeoenvironmental analysis, including authenticated sedimentary ancient DNA (sedaDNA), at Seven Springs, Martlesham, UK, indicating that the springs provided an attractive location for pastoral and ritual activity around a palaeochannel surrounded by dense woodland. We demonstrate that sedaDNA can be preserved well within stratigraphically complex wetland sediment sequences, allowing archaeologically valuable insights into crucial periods of change in the prehistoric, where other forms of environmental evidence can be scarce.

ecology↗

bioRxiv2023

Evolution of sex differences in cooperation:the role of trade-offs with dispersal

AbstractExplaining the evolution of sex differences in cooperation remains a major challenge. Comparative studies highlight that offspring of the more philopatric sex tend to be more cooperative within their family groups than those of the more dispersive sex but we do not understand why. The leading Philopatry hypothesis proposes that the more philopatric sex cooperates more because their higher likelihood of natal breeding increases the direct fitness benefits of natal cooperation. However, the Dispersal trade-off hypothesis proposes that the more dispersive sex cooperates less because preparations for dispersal, such as extra-territorial prospecting, trade-off against natal cooperation. Here, we test both hypotheses in cooperatively breeding white-browed sparrow weavers (Plocepasser mahali), using a novel high-resolution automated radio-tracking method. First, we show that males are the more dispersive sex (a rare reversal of the typical avian sex-difference in dispersal) and that, consistent with the predictions of both hypotheses, females contribute substantially more than males to cooperative care while within the natal group. However, the Philopatry hypothesis cannot readily explain this female-biased cooperation, as females are not more likely than males to breed within their natal group. Instead, our radio-tracking findings support the Dispersal trade-off hypothesis: males conduct pre-dispersal extra-territorial prospecting forays at higher rates than females and prospecting appears to trade-off against natal cooperation. Our findings thus highlight that the evolution of sex differences in cooperation could be widely attributable to trade-offs between cooperation and dispersal; a potentially general explanation that does not demand that cooperation yields direct fitness benefits.

evolutionary biology↗

bioRxiv2023

Consideration of a liquid mutation accumulation experiment to measure mutation rates by successive serial dilution.

The mutation-accumulation (MA) experiment is a fixture of evolutionary biology, though it is laborious to perform. MA experiments typically take between months and years to acquire sufficient mutations to measure DNA mutation rates and mutation spectra. MA experiments for many organisms rely on colony formation on agar plates and repetitive streaking, an environment which at first glance appears somewhat contrived, a poor imitation of real environmental living conditions. We propose that a fully liquid-phase mutation-accumulation experiment may at times more accurately reflect the environment of an organism. We note also that whereas automation of streaking plates is a daunting prospect, automation of liquid handling and serial dilution is already commonplace. In principle, this type of MA experiment can be automated so as to reduce the human capital requirements of measuring mutation rates. We demonstrate that a liquid MA recapitulates the mutation rate estimated for MMR- E. coli in liquid LB culture vs. plate LB culture. We detect a modified mutation spectrum with a transition skew of 4:1 of A:T[->]G:C vs G:C[->]A:T mutations, highlighting the potential role of tautomerization as a DNA mutation mechanism. We also find that using a plate reader to measure OD600 as a proxy for cell growth to be incapable of measuring carrying capacity for MA lines burdened with many mutations.

microbiology↗