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Molecular Biology and Evolution Jun 2024Maintaining genome integrity is vital for organismal survival and reproduction. Essential, broadly conserved DNA repair pathways actively preserve genome integrity....
Maintaining genome integrity is vital for organismal survival and reproduction. Essential, broadly conserved DNA repair pathways actively preserve genome integrity. However, many DNA repair proteins evolve adaptively. Ecological forces like UV exposure are classically cited drivers of DNA repair evolution. Intrinsic forces like repetitive DNA, which also imperil genome integrity, have received less attention. We recently reported that a Drosophila melanogaster-specific DNA satellite array triggered species-specific, adaptive evolution of a DNA repair protein called Spartan/MH. The Spartan family of proteases cleave hazardous, covalent crosslinks that form between DNA and proteins ("DNA-protein crosslink repair"). Appreciating that DNA satellites are both ubiquitous and universally fast-evolving, we hypothesized that satellite DNA turnover spurs adaptive evolution of DNA-protein crosslink repair beyond a single gene and beyond the D. melanogaster lineage. This hypothesis predicts pervasive Spartan gene family diversification across Drosophila species. To study the evolutionary history of the Drosophila Spartan gene family, we conducted population genetic, molecular evolution, phylogenomic, and tissue-specific expression analyses. We uncovered widespread signals of positive selection across multiple Spartan family genes and across multiple evolutionary timescales. We also detected recurrent Spartan family gene duplication, divergence, and gene loss. Finally, we found that ovary-enriched parent genes consistently birthed functionally diverged, testis-enriched daughter genes. To account for Spartan family diversification, we introduce a novel mechanistic model of antagonistic coevolution that links DNA satellite evolution and adaptive regulation of Spartan protease activity. This framework promises to accelerate our understanding of how DNA repeats drive recurrent evolutionary innovation to preserve genome integrity.
Topics: Animals; Evolution, Molecular; Gene Duplication; DNA Repair; Drosophila Proteins; Phylogeny; Drosophila melanogaster; Drosophila; Multigene Family; Selection, Genetic; DNA, Satellite
PubMed: 38865490
DOI: 10.1093/molbev/msae113 -
Molecular Biology of the Cell Jun 2024The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein...
The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein SPC105R/KNL1 in driving meiosis I chromosome segregation through lateral attachments to microtubules and co-orientation of sister centromeres. To identify the domains of SPC105R that are critical for meiotic chromosome segregation, an RNAi-resistant gene expression system was developed. We found that the SPC105R C-terminal domain (aa 1284-1960) is necessary and sufficient for recruiting NDC80 to the kinetochore and building the outer kinetochore. Furthermore, the C-terminal domain recruits BUBR1, which in turn recruits the cohesion protection proteins MEI-S332 and PP2A. Of the remaining 1283 amino acids, we found the first 473 are most important for meiosis. The first 123 amino acids of the N-terminal half of SPC105R contain the conserved SLRK and RISF motifs that are targets of PP1 and Aurora B kinase and are most important for regulating the stability of microtubule attachments and maintaining metaphase I arrest. The region between amino acids 124 and 473 are required for lateral microtubule attachments and bi-orientation of homologs, which are critical for accurate chromosome segregation in meiosis I.
PubMed: 38865189
DOI: 10.1091/mbc.E24-02-0067 -
Journal of Agricultural and Food... Jun 2024The cotton aphid, , is a polyphagous pest that stunts host plant growth via direct feeding or transmitting plant virus. Due to the long-term application of insecticides,...
The cotton aphid, , is a polyphagous pest that stunts host plant growth via direct feeding or transmitting plant virus. Due to the long-term application of insecticides, has developed different levels of resistance to numerous insecticides. We found that five field populations had evolved multiple resistances to neonicotinoids. To explore the resistance mechanism mediated by uridine diphosphate glycosyltransferases (UGTs), two upregulated UGT genes in these five strains, and , were selected for functional analysis of their roles in neonicotinoid detoxification. Transgenic bioassay results indicated that compared with the control lines, the and overexpression lines were more tolerant to thiamethoxam, imidacloprid, and dinotefuran. Knockdown of and significantly increased sensitivity to thiamethoxam, imidacloprid, and dinotefuran. Molecular docking analysis demonstrated that these neonicotinoids could bind to the active pockets of UGT350C3 and UGT344L7. This study provides functional evidence of neonicotinoid detoxification mediated by UGTs and will facilitate further work to identify strategies for preventing the development of neonicotinoid resistance in insects.
Topics: Animals; Aphids; Neonicotinoids; Insecticides; Insecticide Resistance; Glycosyltransferases; Nitro Compounds; Molecular Docking Simulation; Insect Proteins; Thiamethoxam; Drosophila; Guanidines
PubMed: 38864686
DOI: 10.1021/acs.jafc.4c02682 -
Development (Cambridge, England) Jul 2024Tissue morphogenesis is often controlled by actomyosin networks pulling on adherens junctions (AJs), but junctional myosin levels vary. At an extreme, the Drosophila...
Tissue morphogenesis is often controlled by actomyosin networks pulling on adherens junctions (AJs), but junctional myosin levels vary. At an extreme, the Drosophila embryo amnioserosa forms a horseshoe-shaped strip of aligned, spindle-shaped cells lacking junctional myosin. What are the bases of amnioserosal cell interactions and alignment? Compared with surrounding tissue, we find that amnioserosal AJ continuity has lesser dependence on α-catenin, the mediator of AJ-actomyosin association, and greater dependence on Bazooka/Par-3, a junction-associated scaffold protein. Microtubule bundles also run along amnioserosal AJs and support their long-range curvilinearity. Amnioserosal confinement is apparent from partial overlap of its spindle-shaped cells, its outward bulging from surrounding tissue and from compressive stress detected within the amnioserosa. Genetic manipulations that alter amnioserosal confinement by surrounding tissue also result in amnioserosal cells losing alignment and gaining topological defects characteristic of nematically ordered systems. With Bazooka depletion, confinement by surrounding tissue appears to be relatively normal and amnioserosal cells align despite their AJ fragmentation. Overall, the fully elongated amnioserosa appears to form through tissue-autonomous generation of spindle-shaped cells that nematically align in response to confinement by surrounding tissue.
Topics: Animals; Drosophila Proteins; Adherens Junctions; Embryonic Development; Microtubules; Drosophila melanogaster; Embryo, Nonmammalian; alpha Catenin; Actomyosin; Morphogenesis; Drosophila; Cell Shape; Intracellular Signaling Peptides and Proteins
PubMed: 38864272
DOI: 10.1242/dev.202577 -
Nature Communications Jun 2024Twisted gastrulation (TWSG1) is an evolutionarily conserved secreted glycoprotein which controls signaling by Bone Morphogenetic Proteins (BMPs). TWSG1 binds BMPs and...
Twisted gastrulation (TWSG1) is an evolutionarily conserved secreted glycoprotein which controls signaling by Bone Morphogenetic Proteins (BMPs). TWSG1 binds BMPs and their antagonist Chordin to control BMP signaling during embryonic development, kidney regeneration and cancer. We report crystal structures of TWSG1 alone and in complex with a BMP ligand, Growth Differentiation Factor 5. TWSG1 is composed of two distinct, disulfide-rich domains. The TWSG1 N-terminal domain occupies the BMP type 1 receptor binding site on BMPs, whereas the C-terminal domain binds to a Chordin family member. We show that TWSG1 inhibits BMP function in cellular signaling assays and mouse colon organoids. This inhibitory function is abolished in a TWSG1 mutant that cannot bind BMPs. The same mutation in the Drosophila TWSG1 ortholog Tsg fails to mediate BMP gradient formation required for dorsal-ventral axis patterning of the early embryo. Our studies reveal the evolutionarily conserved mechanism of BMP signaling inhibition by TWSG1.
Topics: Animals; Bone Morphogenetic Proteins; Signal Transduction; Mice; Humans; Drosophila Proteins; Glycoproteins; Intercellular Signaling Peptides and Proteins; Binding Sites; Protein Domains; Protein Binding; Organoids; HEK293 Cells; Gastrulation; Mutation; Crystallography, X-Ray; Drosophila melanogaster; Proteins
PubMed: 38862520
DOI: 10.1038/s41467-024-49065-8 -
Aging Jun 2024The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly . It is noteworthy that lithium is attributed with insulin-like...
The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly . It is noteworthy that lithium is attributed with insulin-like activity as it stimulates protein kinase B/Akt and suppresses the activity of glycogen synthase kinase-3 (GSK-3). However, its interaction with dietary sugar has largely remained unexplored. Therefore, we investigated the effects of lithium supplementation on known lithium-sensitive parameters in fruit flies, such as lifespan, body composition, GSK-3 phosphorylation, and the transcriptome, while varying the dietary sugar concentration. For all these parameters, we observed that the efficacy of lithium was significantly influenced by the sucrose content in the diet. Overall, we found that lithium was most effective in enhancing longevity and altering body composition when added to a low-sucrose diet. Whole-body RNA sequencing revealed a remarkably similar transcriptional response when either increasing dietary sucrose from 1% to 10% or adding 1 mM LiCl to a 1% sucrose diet, characterized by a substantial overlap of nearly 500 differentially expressed genes. Hence, dietary sugar supply is suggested as a key factor in understanding lithium bioactivity, which could hold relevance for its therapeutic applications.
Topics: Animals; Drosophila melanogaster; Longevity; Dietary Sucrose; Gene Expression Regulation; Glycogen Synthase Kinase 3; Lithium; Lithium Chloride; Phosphorylation; Drosophila Proteins
PubMed: 38862239
DOI: 10.18632/aging.205933 -
Learning & Memory (Cold Spring Harbor,... May 2024The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we...
The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.
Topics: Animals; Mushroom Bodies; Presynaptic Terminals; Drosophila Proteins; Memory; rab3 GTP-Binding Proteins; Nerve Tissue Proteins; Drosophila; Synaptic Vesicles
PubMed: 38862173
DOI: 10.1101/lm.054013.124 -
PLoS Pathogens Jun 2024Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by the same pathogen can 'prime' the immune...
Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by the same pathogen can 'prime' the immune response, resulting in improved survival upon reinfection. Here, we investigated the mechanistic basis and epidemiological consequences of innate immune priming in the fruit fly Drosophila melanogaster when infected with the gram-negative bacterial pathogen Providencia rettgeri. We find that priming in response to P. rettgeri infection is a long-lasting and sexually dimorphic response. We further explore the epidemiological consequences of immune priming and find it has the potential to curtail pathogen transmission by reducing pathogen shedding and spread. The enhanced survival of individuals previously exposed to a non-lethal bacterial inoculum coincided with a transient decrease in bacterial loads, and we provide strong evidence that the effect of priming requires the IMD-responsive antimicrobial-peptide Diptericin-B in the fat body. Further, we show that while Diptericin B is the main effector of bacterial clearance, it is not sufficient for immune priming, which requires regulation of IMD by peptidoglycan recognition proteins. This work underscores the plasticity and complexity of invertebrate responses to infection, providing novel experimental evidence for the effects of innate immune priming on population-level epidemiological outcomes.
Topics: Animals; Immunity, Innate; Drosophila melanogaster; Providencia; Drosophila Proteins; Female; Male; Enterobacteriaceae Infections; Antimicrobial Peptides
PubMed: 38857285
DOI: 10.1371/journal.ppat.1012308 -
ArXiv May 2024Morphogenesis is the process whereby the body of an organism develops its target shape. The morphogen BMP is known to play a conserved role across bilaterian organisms...
Morphogenesis is the process whereby the body of an organism develops its target shape. The morphogen BMP is known to play a conserved role across bilaterian organisms in determining the dorsoventral (DV) axis. Yet, how BMP governs the spatio-temporal dynamics of cytoskeletal proteins driving morphogenetic flow remains an open question. Here, we use machine learning to mine a morphodynamic atlas of Drosophila development, and construct a mathematical model capable of predicting the coupled dynamics of myosin, E-cadherin, and morphogenetic flow. Mutant analysis shows that BMP sets the initial condition of this dynamical system according to the following signaling cascade: BMP establishes DV pair-rule-gene patterns that set-up an E-cadherin gradient which in turn creates a myosin gradient in the opposite direction through mechanochemical feedbacks. Using neural tube organoids, we argue that BMP, and the signaling cascade it triggers, prime the conserved dynamics of neuroectoderm morphogenesis from fly to humans.
PubMed: 38855544
DOI: No ID Found -
Developmental Cell Jun 2024Organisms have evolved strategies to store resources and overcome periods of low or no nutrient access, including transient shortages or longer non-feeding developmental...
Organisms have evolved strategies to store resources and overcome periods of low or no nutrient access, including transient shortages or longer non-feeding developmental transitions. Holometabolous insects like Drosophila represent an attractive model to study resource allocation during development because they alternate feeding and non-feeding periods. Amino acids are essential components for tissue growth and renewal, but the strategies used for their storage remain largely unexplored. Here, we characterize the molecular mechanisms for the temporal production, accumulation, and use of specific storage proteins called hexamerins, and demonstrate their role in ensuring tissue formation and adult fitness. Moreover, we show that preventing hexamerin stores enhances the growth of early-developing organs while compromising the emergence of late-forming ones, consequently altering body allometry.
PubMed: 38851190
DOI: 10.1016/j.devcel.2024.05.018