bioRxiv : the preprint server for biology最新文献_第2页

Combined MEG and EEG suggest a limbic source network of the P3 including retrosplenial cortex and hippocampus. 脑电和脑磁图显示在脾后皮质、脑岛和海马体中存在P3的边缘源网络。

bioRxiv : the preprint server for biology Pub Date : 2025-05-24 DOI: 10.1101/2025.03.24.645008

Diptyajit Das, Matti S Hämäläinen, Andrew R Dykstra, Andre Rupp, Alexander Gutschalk

{"title":"Combined MEG and EEG suggest a limbic source network of the P3 including retrosplenial cortex and hippocampus.","authors":"Diptyajit Das, Matti S Hämäläinen, Andrew R Dykstra, Andre Rupp, Alexander Gutschalk","doi":"10.1101/2025.03.24.645008","DOIUrl":"10.1101/2025.03.24.645008","url":null,"abstract":"The P3 is evoked by most target and salient distractor stimuli, but its neural generators have remained controversial. Here we reevaluate the role of retro-splenial cortex and hippocampus as potential generators of the P3. Combined magneto- and electroencephalography signals were recorded during a visual oddball paradigm. Observers were instructed to respond to rare targets of a deviant shape and ignore rare non-targets of a deviant color. Source analysis was based on noise-normalized minimum norm estimates in an individual, MRI-based cortical source space. Critically, the source space was extended with the hippocampus. Source analysis showed strong sources in retrosplenial cortex and hippocampus at the P3 peak. Subsequent activity was observed in insula and anterior mid-cingulate cortex. The source configuration was similar for rare target and non-target stimuli. Simulations and further analyses show that the source in retrosplenial cortex is strongly attenuated in magnetoencephalography, whereas the source in hippocampus contributes to both recording modalities. These data support that retrosplenial cortex is a main generator of the P3 in EEG and that the hippocampal P3 source can be recorded with extracranial EEG and MEG. The source configuration presented here suggests that the P3 is confined to limbic circuits.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Collective unstructured interactions drive chromatin binding of transcription factors. 集体非结构化相互作用驱动转录因子的染色质结合。

bioRxiv : the preprint server for biology Pub Date : 2025-05-23 DOI: 10.1101/2025.05.16.654615

Abrar A Abidi, Gina M Dailey, Robert Tjian, Thomas G W Graham

{"title":"Collective unstructured interactions drive chromatin binding of transcription factors.","authors":"Abrar A Abidi, Gina M Dailey, Robert Tjian, Thomas G W Graham","doi":"10.1101/2025.05.16.654615","DOIUrl":"https://doi.org/10.1101/2025.05.16.654615","url":null,"abstract":"Eukaryotic transcription factors (TFs) contain both structured DNA-binding domains (DBDs) and intrinsically disordered regions (IDRs). While the structures and sequence preferences of DBDs have been extensively characterized, the role of IDR-mediated interactions in chromatin binding and nuclear organization remains poorly understood, in part because these interactions have been difficult to measure in living cells. Here, we use a recently developed single-molecule technique, proximity-assisted photoactivation (PAPA), to investigate how IDRs influence TF associations with each other and with chromatin, focusing on the factors Sp1 and Klf1. We find that the number and patterning of aromatic and basic residues within IDRs govern both TF self-association and chromatin binding. Unexpectedly, the isolated DBD of Sp1 binds chromatin very weakly and non-specifically. The isolated IDR, by contrast, interacts poorly with chromatin-bound wild-type Sp1, yet this interaction is enhanced when even minimal DNA-binding capacity is restored. Strikingly, replacing Sp1's native DBD with those of heterologous TFs recovers both IDR-mediated interactions and chromatin association, despite divergent sequence preferences. PAPA measurements also reveal extensive heterotypic interactions between wild-type Sp1 and other TFs. Together, these results establish PAPA as a powerful method for studying unstructured interactions in their native context and suggest that IDRs participate in widespread cooperative associations scaffolded by transient DBD-DNA contacts, which concentrate disordered regions along chromatin. In contrast to classical models, we propose that TF specificity in vivo emerges not solely from DBD sequence preferences, but from a constellation of weak, dynamic, and diverse interactions mediated by IDRs.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trikafta rescues F508del-CFTR by tightening specific phosphorylation-dependent interdomain interactions. Trikafta 通过加强特定的磷酸化依赖性域间相互作用来挽救 F508del-CFTR 。

bioRxiv : the preprint server for biology Pub Date : 2025-05-23 DOI: 10.1101/2024.11.20.624197

Guangyu Wang

{"title":"Trikafta rescues F508del-CFTR by tightening specific phosphorylation-dependent interdomain interactions.","authors":"Guangyu Wang","doi":"10.1101/2024.11.20.624197","DOIUrl":"10.1101/2024.11.20.624197","url":null,"abstract":"Trikafta effectively corrects the thermal and gating defects associated with the F508del mutation, the most common cause of cystic fibrosis, even at physiological temperatures. However, the exact correction pathway is still unclear. Here, noncovalent interactions among two transmembrane domains (TMD1 and TMD2), the regulatory (R) domain and two nucleotide binding domains (NBD1 and NBD2) were analyzed. The thermal stability of NBD1 was also evaluated through its tertiary constrained noncovalent interaction networks or thermoring structures. The results demonstrated that Trikafta binding to flexible TMD1 and TMD2 rearranged their interactions with the R domain upon phosphorylation, coupling tightened cytoplasmic TMD1-TMD2 interactions to tightened Mg/ATP-dependent NBD1-NBD2 dimerization, which stabilized NBD1 above human body temperature. In essence, while the F508 deletion primarily causes a thermal defect in NBD1, leading to a gating defect at the TMD1-TMD2 interface, Trikafta allosterically reverses these effects. These mechanistic insights into the precise correction pathway of this misfolded channel facilitate optimizing cystic fibrosis treatment. (155 words).Key points: Trikafta binding to flexible TMD1 and TMD2 tightened their cytoplasmic interactions.Tight cytoplasmic TMD1-TMD2 interactions primed the specific binding of the dynamic phosphorylated S813 site to the TMD1/TMD2/NBD1 interfaces.The tight binding of the S813 site to the TMD1/TMD2/NBD1 interfaces strengthened NBD1-NBD2 dimerization which stabilizes NBD1.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Muscarinic acetylcholine receptor activated effectors in principal neurons of the rat basolateral amygdala. 毒蕈碱1型受体激活大鼠基底外侧杏仁核主要神经元中的效应器。

bioRxiv : the preprint server for biology Pub Date : 2025-05-23 DOI: 10.1101/2025.03.14.643393

Todd J Sahagian, Scott W Harden, Jennifer L Bizon, Barry Setlow, Charles J Frazier

{"title":"Muscarinic acetylcholine receptor activated effectors in principal neurons of the rat basolateral amygdala.","authors":"Todd J Sahagian, Scott W Harden, Jennifer L Bizon, Barry Setlow, Charles J Frazier","doi":"10.1101/2025.03.14.643393","DOIUrl":"10.1101/2025.03.14.643393","url":null,"abstract":"The basolateral amygdala (BLA) plays a crucial role in context-specific learning and memory by integrating valence-specific stimuli with internal physiological states. Cholinergic signaling systems modulate neural excitability to influence information processing in the BLA. Muscarinic acetylcholine receptors (mAChRs) are of particular interest because aberrant mAChR signaling in BLA circuits is associated with neuropsychiatric disorders, cognitive impairment, substance use, and age-related cognitive decline. This study evaluates mAChR activation in BLA principal neurons (PNs) in juvenile rat brain slices using whole-cell patch-clamp recordings. We found that bath application of carbachol (CCh,) produces a pirenzepine sensitive excitatory response in BLA PNs voltage clamped near the resting potential, which depends on an underlying biphasic change in membrane resistance, indicating an involvement of multiple effectors. More specifically, we observed that CCh excites BLA PNs by inhibiting the afterhyperpolarization (AHP), by reducing a steady state inhibitory current, and by promoting an afterdepolarization (ADP). We further identify and characterize a CCh-induced and calcium-activated non-selective cation current (I CAN ) that underlies the ADP in voltage clamp. Overall, our findings provide new insights into specific effectors modulated by activation of pirenzepine sensitive mAChRs expressed by BLA PNs. We also reveal new details about the time-and voltage-dependence of current carried by the CCh - activated I CAN like current in BLA PNs, and highlight its ability to promote a suprathreshold ADP capable of generating sustained firing after a brief excitatory stimulus. Improved understanding of these effectors will provide potentially valuable new insights on the wide range of mechanisms through which cholinergic system dysfunction can lead to impaired executive function.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypic tolerance for rDNA copy number variation within the natural range of C. elegans. 秀丽隐杆线虫自然范围内rDNA拷贝数变异的表型耐受性。

bioRxiv : the preprint server for biology Pub Date : 2025-05-22 DOI: 10.1101/2025.03.21.644675

Ashley N Hall, Elizabeth A Morton, Rebecca Walters, Josh T Cuperus, Christine Queitsch

{"title":"Phenotypic tolerance for rDNA copy number variation within the natural range of C. elegans.","authors":"Ashley N Hall, Elizabeth A Morton, Rebecca Walters, Josh T Cuperus, Christine Queitsch","doi":"10.1101/2025.03.21.644675","DOIUrl":"10.1101/2025.03.21.644675","url":null,"abstract":"The genes for ribosomal RNA (rRNA) are encoded by ribosomal DNA (rDNA), whose structure is notable for being present in arrays of tens to thousands of tandemly repeated copies in eukaryotic genomes. The exact number of rDNA copies per genome is highly variable within a species, with differences between individuals measuring in potentially hundreds of copies and megabases of DNA. The extent to which natural variation in rDNA copy number impacts whole-organism phenotypes such as fitness and lifespan is poorly understood, in part due to difficulties in manipulating such large and repetitive tracts of DNA even in model organisms. Here, we used the natural resource of copy number variation in C. elegans wild isolates to generate new tools and investigated the phenotypic consequences of this variation. Specifically, we generated a panel of recombinant inbred lines (RILs) using a laboratory strain derivative with ∼130 haploid rDNA copies and a wild isolate with ∼417 haploid rDNA copies, one of the highest validated C. elegans rDNA copy number arrays. We find that rDNA copy number is stable in the RILs, rejecting prior hypotheses that predicted copy number instability and copy number reversion. To isolate effects of rDNA copy number on phenotype, we produced a series of near isogenic lines (NILs) with rDNA copy numbers representing the high and low end of the rDNA copy number spectrum in C. elegans wild isolates. We find no correlation between rDNA copy number and phenotypes of rRNA abundance, competitive fitness, early life fertility, lifespan, or global transcriptome under standard laboratory conditions. These findings demonstrate a remarkable ability of C. elegans to tolerate substantial variation in a locus critical to fundamental cell function. Our study provides strain resources for future investigations into the boundaries of this tolerance.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternatives to Friction Coefficient: Fine Touch Perception Correlates with Frictional Instabilities. 摩擦系数的替代品：精细触感依赖于摩擦不稳定性

bioRxiv : the preprint server for biology Pub Date : 2025-05-22 DOI: 10.1101/2024.10.25.620351

Maryanne Derkaloustian, Pushpita Bhattacharyya, Truc Ngo, Joshua G A Cashaback, Jared Medina, Charles B Dhong

{"title":"Alternatives to Friction Coefficient: Fine Touch Perception Correlates with Frictional Instabilities.","authors":"Maryanne Derkaloustian, Pushpita Bhattacharyya, Truc Ngo, Joshua G A Cashaback, Jared Medina, Charles B Dhong","doi":"10.1101/2024.10.25.620351","DOIUrl":"10.1101/2024.10.25.620351","url":null,"abstract":"Fine touch perception is often correlated to material properties and friction coefficients, but the inherent variability of human motion has led to low correlations and contradictory findings. Instead, we hypothesized that humans use frictional instabilities to discriminate between objects. Here, we constructed a set of coated surfaces with minimal physical differences, but due to differences in surface chemistry, generated different types of instabilities depending on how quickly a finger is slid and pressed during sliding. In one experiment, we used a mechanical mock finger to quantify and classify differences in instability formation from different coated surfaces. In a second experiment, participants perform a discrimination task using the same coated surfaces. Using the data from these two experiments, we found that human discrimination response times were faster with surfaces where the mock finger produced more stiction spikes and discrimination accuracy was higher where the mock finger produced more steady sliding. Conversely, traditional metrics like surface roughness or average friction coefficient did not relate to tactile discriminability. In fact, the typical method of averaging friction coefficients led to a spurious correlation which erroneously suggests that distinct objects should feel identical and identical objects should feel distinct-similar to findings by others. Friction instabilities may offer a more predictive and tractable framework of fine touch perception than friction coefficients, which would accelerate the design of tactile interfaces.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New alleles of D-2-hydroxyglutarate dehydrogenase enable studies of oncometabolite function in Drosophila melanogaster. d -2-羟戊二酸脱氢酶的新等位基因使黑腹果蝇肿瘤代谢功能的研究成为可能。

bioRxiv : the preprint server for biology Pub Date : 2025-05-22 DOI: 10.1101/2025.03.27.645621

Madhulika Rai, Prince Okah, Shefali A Shefali, Alexander J Fitt, Michael Z Shen, Mandkhai Molomjamts, Robert Pepin, Travis Nemkov, Angelo D'Alessandro, Jason M Tennessen

{"title":"New alleles of D-2-hydroxyglutarate dehydrogenase enable studies of oncometabolite function in Drosophila melanogaster.","authors":"Madhulika Rai, Prince Okah, Shefali A Shefali, Alexander J Fitt, Michael Z Shen, Mandkhai Molomjamts, Robert Pepin, Travis Nemkov, Angelo D'Alessandro, Jason M Tennessen","doi":"10.1101/2025.03.27.645621","DOIUrl":"10.1101/2025.03.27.645621","url":null,"abstract":"D-2-hydroxyglutarate (D-2HG) is a potent oncometabolite capable of disrupting chromatin architecture, altering metabolism, and promoting cellular dedifferentiation. As a result, ectopic D-2HG accumulation induces neurometabolic disorders and promotes progression of multiple cancers. However, the disease-associated effects of ectopic D-2HG accumulation are dependent on genetic context. Specifically, neomorphic mutations in the mammalian genes Isocitrate dehydrogenase 1 ( IDH1 ) and IDH2 result in the production of enzymes that inappropriately generate D-2HG from α-ketoglutarate (αKG). Within this genetic background, D-2HG acts as an oncometabolite and is associated with multiple cancers, including several diffuse gliomas. In contrast, loss-of-function mutations in the gene D-2-hydroxyglutarate dehydrogenase (D2hgdh) render cells unable to degrade D-2HG, resulting in excessive buildup of this molecule. D2hgdh mutations, however, are not generally associated with elevated cancer risk. This discrepancy raises the question as to why ectopic D-2HG accumulation in humans induces context-dependent disease outcomes. To enable such genetic studies in vivo , we generated two novel loss-of-function mutations in the Drosophila melanogaster gene D2hgdh and validated that these alleles result in ectopic D-2HG. Moreover, we observed that D2hgdh mutations induce developmental and metabolomic phenotypes indicative of elevated D-2HG accumulation. Overall, our efforts provide the Drosophila community with new mutant strains that can be used to study D-2HG function in human disease models as well as in the context of normal growth, metabolism, and physiology.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac-specific GCN5L1 deficiency promotes MASLD in HFpEF. 心脏特异性GCN5L1缺失可促进HFpEF患者的脂肪肝疾病。

bioRxiv : the preprint server for biology Pub Date : 2025-05-21 DOI: 10.1101/2025.02.05.636634

Paramesha Bugga, Bellina A S Mushala, Michael W Stoner, Janet R Manning, Nisha Bhattarai, Maryam Sharifi-Sanjani, Amber Vandevender, Raja G R Mooli, Sadeesh K Ramakrishnan, Brett A Kaufman, Sruti S Shiva, Cassandra L Happe, Steven J Mullet, Stacy L Gelhaus, Michael J Jurczak, Iain Scott

{"title":"Cardiac-specific GCN5L1 deficiency promotes MASLD in HFpEF.","authors":"Paramesha Bugga, Bellina A S Mushala, Michael W Stoner, Janet R Manning, Nisha Bhattarai, Maryam Sharifi-Sanjani, Amber Vandevender, Raja G R Mooli, Sadeesh K Ramakrishnan, Brett A Kaufman, Sruti S Shiva, Cassandra L Happe, Steven J Mullet, Stacy L Gelhaus, Michael J Jurczak, Iain Scott","doi":"10.1101/2025.02.05.636634","DOIUrl":"10.1101/2025.02.05.636634","url":null,"abstract":"The prevalence of cardiometabolic heart failure with preserved ejection fraction (HFpEF) continues to grow, representing over half of heart failure cases in the United States. As no specific medication for HFpEF exists, treatment guidelines focus on the management of comorbidities related to metabolic syndrome (e.g. obesity, diabetes, hypertension) that promote the disease1. These same comorbidities also drive pathology in non-cardiac tissues, and the links between cardiometabolic disease presentations in different organs are increasingly being recognized. Preclinical studies on the potential crosstalk between HFpEF and metabolic disease in the liver (e.g. metabolic dysfunction-associated liver disease; MASLD) have focused on how liver dysfunction may affect the heart, particularly through the release of secreted liver proteins. This may reflect the situation in the clinic, where incident MASLD is a risk factor for future HFpEF development. Here, in contrast to this developing paradigm of liver-initiated cardiac disease, we report for the first time a defect in cardiac metabolism related to the mitochondrial metabolic protein GCN5L1 that drives hepatic steatosis and MASLD in HFpEF.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolution of sensory systems underlies the emergence of predatory feeding behaviours in nematodes. 感觉系统的进化是线虫出现掠夺性摄食行为的基础。

bioRxiv : the preprint server for biology Pub Date : 2025-05-21 DOI: 10.1101/2025.03.24.644997

Marianne Roca, Güniz Göze Eren, Leonard Böger, Olena Didenko, Wen-Sui Lo, Monika Scholz, James W Lightfoot

{"title":"Evolution of sensory systems underlies the emergence of predatory feeding behaviours in nematodes.","authors":"Marianne Roca, Güniz Göze Eren, Leonard Böger, Olena Didenko, Wen-Sui Lo, Monika Scholz, James W Lightfoot","doi":"10.1101/2025.03.24.644997","DOIUrl":"10.1101/2025.03.24.644997","url":null,"abstract":"Understanding how animal behaviour evolves remains a major challenge, with few studies linking genetic changes to differences in neural function and behaviour across species. Here, we identify specific sensory adaptations associated with the emergence of predatory feeding behaviours in the nematode Pristionchus pacificus . While Caenorhabditis elegans uses contact-dependent sensing primarily to avoid threats, Pristionchus pacificus has co-opted this modality to support both avoidance and prey detection, enabling context-dependent predatory behaviour. To uncover a potential mechanism underlying the evolution of P. pacificus prey perception, we mutated 27 canonical mechanosensory genes and assessed their function using behavioural assays, automated behavioural tracking, and a machine learning analysis of behavioural states. While several mutants showed mechanosensory defects, Ppa-mec-6 mutants specifically also impaired prey detection, indicating the emergence of a novel mechanosensory module linked to predatory behaviour. Furthermore, disrupting both mechanosensation alongside chemosensation revealed a synergistic influence for these modalities. Crucially, both mechanosensation and chemosensation pathways converge in the same environmentally exposed IL2 neurons, and silencing these cells induced severe predation defects validating their importance for prey sensing. Thus, predation evolved through the co-option of mechanosensory and chemosensory systems that act together to shape the evolution of complex behavioural traits.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates. 在中间尺度评估基因内的选择为结核分枝杆菌临床分离株的阳性选择提供了强有力的基因鉴定。

bioRxiv : the preprint server for biology Pub Date : 2025-05-20 DOI: 10.1101/2025.05.07.652684

Thomas R Ioerger, Anthony Shatby

{"title":"Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.","authors":"Thomas R Ioerger, Anthony Shatby","doi":"10.1101/2025.05.07.652684","DOIUrl":"https://doi.org/10.1101/2025.05.07.652684","url":null,"abstract":"Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) provides the most credible list of candidate genes under selection. A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 178 significant genes under selection, with 36% overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection ( resR, phoR ). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0