Genetics最新文献_第2页

Drug screens using the nematode Caenorhabditis elegans. 利用秀丽隐杆线虫进行药物筛选。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf141

Peter J Roy

引用次数: 0

Alleles of Chaser, a dominant modifier of the Drosophila melanogaster foraging gene, are consistent with variegating alleles of the heterochromatic gene spookier. 黑腹果蝇觅食基因的显性修饰基因Chaser的等位基因与异色基因spookier的变异等位基因一致。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf123

Alistair B Coulthard, Richard Yuditskiy, Alexander R Molnar, Qaim Ali Ramazan, Marla B Sokolowski, Arthur J Hilliker

{"title":"Alleles of Chaser, a dominant modifier of the Drosophila melanogaster foraging gene, are consistent with variegating alleles of the heterochromatic gene spookier.","authors":"Alistair B Coulthard, Richard Yuditskiy, Alexander R Molnar, Qaim Ali Ramazan, Marla B Sokolowski, Arthur J Hilliker","doi":"10.1093/genetics/iyaf123","DOIUrl":"10.1093/genetics/iyaf123","url":null,"abstract":"The relationship between genes and quantitative behavioral traits involves complex regulatory networks. Identifying genes that operate in these regulatory pathways can be challenging, especially when dealing with dominant genetic factors. Our work has focused on a naturally occurring behavioral polymorphism in larval foraging behavior in Drosophila melanogaster. This polymorphism in larval foraging behavior arises from variation in the foraging (for) gene with its rover and sitter naturally occurring variants. The dominant rover allele (forR) results in larvae which move longer distances while foraging compared with larvae with the recessive sitter (fors) alleles. In this article, we report the successful mapping of the Chaser (Csr) gene, a dominant modifier of larval foraging behavior which makes sitter larvae behave in a rover-like manner. We localized Csr by first mapping recessive phenotype tags closely linked to Csr. These phenotype tags mapped to the centromeric heterochromatin on the right arm of chromosome 3. We showed through a combination of deletion mapping, qRT-PCR and feeding of ecdysone hormone to larvae during development that the alleles of Csr are consistent with variegating alleles of the gene spookier (spok). With spok being an essential gene in the synthesis of the molting hormone ecdysone, we have established a link between ecdysone signaling and larval foraging behavior in D. melanogaster.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long telomere inheritance through budding yeast sexual cycles. 芽殖酵母性周期中的长端粒遗传。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf129

Vasilisa Sidarava, Sarah Mearns, David Lydall

{"title":"Long telomere inheritance through budding yeast sexual cycles.","authors":"Vasilisa Sidarava, Sarah Mearns, David Lydall","doi":"10.1093/genetics/iyaf129","DOIUrl":"10.1093/genetics/iyaf129","url":null,"abstract":"The ends of linear eukaryotic chromosomes are protected from being recognized as DNA double-strand breaks by telomeres, containing repetitive DNA sequences that bind specific proteins. In humans, mutations in telomere regulatory genes lead to short or long telomere syndromes. These syndromes often show genetic anticipation, where the disease has an earlier onset and a more severe manifestation in each new generation. Later generations inherit not only the mutation affecting telomere length, but also abnormal telomere length. Many aspects of telomere length homeostasis are conserved between mammals and yeast. Here, we explored telomere length inheritance patterns through the sexual cycle in yeast. Analysis of single telomeres, rather than bulk telomeres, shows that if haploid yeast with short telomeres mate with wild-type yeast, creating diploids, short telomere lengths rapidly normalize (within 30 cell divisions). However, long telomeres inherited from one parent can persist for more than 200 mitotic cell divisions. Long telomeres can also be transmitted through more than one round of meiosis, independently of mutations that cause long telomeres. These patterns, along with haploinsufficiency effects, show that even in yeast, there is a complex relationship between telomere length, telomere length inheritance, and mutations that affect telomere length. Our findings may have implications for families affected by telomere syndromes.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Excretory gland cell and NSPC genes in C. elegans: investigating their physiological roles. 秀丽隐杆线虫分泌腺细胞和NSPC基因的生理作用研究。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf125

Zuzanna Mackiewicz, Vladyslava Liudkovska, Andrzej Dziembowski

{"title":"Excretory gland cell and NSPC genes in C. elegans: investigating their physiological roles.","authors":"Zuzanna Mackiewicz, Vladyslava Liudkovska, Andrzej Dziembowski","doi":"10.1093/genetics/iyaf125","DOIUrl":"10.1093/genetics/iyaf125","url":null,"abstract":"The nematode Caenorhabditis elegans is one of the best-studied model organisms in molecular biology; however, many aspects of its physiology and the functions of many genes remain poorly understood. In this study, we investigated the role of Nematode-Specific Peptide Family, group C (NSPC) proteins, whose mRNAs were recently identified as primary targets of the poly(A) polymerase TENT-5. Surprisingly, we found that NSPCs are exclusively expressed in the excretory gland cell, a cell with still unclear functionality. Using an optogenetic approach, we precisely ablated the excretory gland cell and observed that, apart from a strong downregulation of NSPCs, nematodes exhibited no transcriptomic or physiological changes in its absence. Additionally, we generated and thoroughly studied a strain with a deletion of all 18 nspc genes, which revealed that, despite previous indications, NSPCs do not influence the worm's defense response. Instead, the transcriptomic analysis showed that the absence of NSPCs results in gene expression changes resembling those observed for DAF-16 mutants, suggesting that NSPCs may somehow influence the key C. elegans insulin signaling pathway. Although further studies are required to explain the exact genetic interaction and elucidate its physiological effects, our findings provide new insights into this unexplored part of nematode physiology.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of a BCOR internal tandem duplication in mouse embryonic stem cell to neuronal precursor differentiation. BCOR内串联复制在小鼠胚胎干细胞向神经元前体细胞分化中的作用分析。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf133

Zuzer Dhoondia, Hyuckjoon Kang, Kwangwoon Lee, Philip A Cole, Mitzi I Kuroda

{"title":"Analysis of a BCOR internal tandem duplication in mouse embryonic stem cell to neuronal precursor differentiation.","authors":"Zuzer Dhoondia, Hyuckjoon Kang, Kwangwoon Lee, Philip A Cole, Mitzi I Kuroda","doi":"10.1093/genetics/iyaf133","DOIUrl":"10.1093/genetics/iyaf133","url":null,"abstract":"BCOR (BCL-6 corepressor) is a component of variant Polycomb Repressive Complex 1.1 (vPRC1.1), one of several vPRC1 complexes that catalyze histone H2A ubiquitination thought to play an important role in PRC2 binding and the deposition of H3K27me3 to silence genes. The PCGF Ub-like fold discriminator (PUFD) domain at the C-terminus of BCOR forms a heterodimer with PCGF1, serving as a critical interface for its polycomb-dependent functions. Internal tandem duplication (ITD) mutations in BCOR, causing in-frame duplications of 20 to 40 amino acids in the PUFD domain, are observed in heterogeneous tumors including sarcomas (kidney, bone, and endometrium) and neuroepithelial tumors in the brain. To dissect the molecular mechanisms underlying aberrant function of BCOR-ITD mutants, we employed mouse embryonic stem (mES) cells expressing either transgenic or endogenous BCOR-ITD. Our results indicate that the BCOR-ITD mutation does not disrupt the BCOR-PCGF1 interaction, instead maintaining the integrity of the vPRC1.1 complex. While displaying subtle changes in imprinted gene expression during differentiation toward a neural lineage, BCOR-ITD mutants also had no growth phenotype in culture. Furthermore, we found that CD24+ cells were enriched, as expected, during neural progenitor differentiation in both wildtype and mutant cells. However, sensitization of BCOR-ITD mES cells with EZH2 inhibitor during differentiation resulted in an unexpected enrichment of a CD24+CD26+ subpopulation, indicating aberrant cell fate that was also prevalent in a BCOR truncation mutant. Together, our results suggest that BCOR-ITD may largely retain wildtype function, but with increased susceptibility to synergistic stress on the Polycomb pathway.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The genetic architecture of quantitative variation in the self-incompatibility response within Phlox drummondii (Polemoniaceae). 竹节夹竹桃自交不亲和反应数量变异的遗传结构。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf132

Grace A Burgin, Federico Roda, Matthew Farnitano, Charles Hale, Antonio Serrato-Capuchina, Robin Hopkins

{"title":"The genetic architecture of quantitative variation in the self-incompatibility response within Phlox drummondii (Polemoniaceae).","authors":"Grace A Burgin, Federico Roda, Matthew Farnitano, Charles Hale, Antonio Serrato-Capuchina, Robin Hopkins","doi":"10.1093/genetics/iyaf132","DOIUrl":"10.1093/genetics/iyaf132","url":null,"abstract":"Flowering plants display extensive variation in selfing rate, a trait with significant ecological and evolutionary consequences. Many species use genetic mechanisms to recognize and reject self-pollen (termed self-incompatibility or SI), and the loss of SI is one of the most common evolutionary transitions among flowering plants. Despite the ubiquity of transitions to self-compatibility (SC), little is known about the genetic architecture through which SC evolves. Specifically, it is important to determine if SC has a simple or polygenic basis and if variation localizes to the self-pollen recognition locus (the \"S-locus\"). Phlox drummondii (Polemoniaceae) is a model system for exploring mating system evolution and expresses range-wide variation in SI. Here, we investigate the genetic architecture of SC variants segregating within this otherwise SI species. Using multiple independent crosses, we uncover numerous QTLs associated with intraspecific SI variation, consistent with a polygenic genetic architecture. While some QTLs overlap across mapping experiments, other QTLs are unique, suggesting that multiple genetic routes to SC exist. We demonstrate that P. drummondii has a sporophytic SI system, revealing an independent evolution of SI within the Phlox lineage. We map this novel S-locus and find that the genomic region containing the S-locus is associated with intraspecific variation in SI in one of the 3 mapping populations. Although further work is necessary to clarify the conditions under which quantitative variation in SI represents a transitional pathway to complete SC, our study reveals the genetic architecture upon which selection could act to drive this frequent and evolutionarily significant transition.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional analysis of human EED variants using Drosophila. 果蝇对人类EED变异的功能分析。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf120

Sharri S Cyrus, Sònia Medina-Giró, Tianshun Lian, Douglas W Allan, William T Gibson

引用次数: 0

CDH-3/Cadherin, YAP-1/YAP and EGL-44/TEAD promote SYX-2/Syntaxin and EFF-1 fusogen-mediated phagosome closure. CDH-3/Cadherin、YAP-1/YAP和EGL-44/TEAD促进SYX-2/Syntaxin和ef -1融合原介导的吞噬体关闭。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf182

Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose

{"title":"CDH-3/Cadherin, YAP-1/YAP and EGL-44/TEAD promote SYX-2/Syntaxin and EFF-1 fusogen-mediated phagosome closure.","authors":"Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose","doi":"10.1093/genetics/iyaf182","DOIUrl":"10.1093/genetics/iyaf182","url":null,"abstract":"Physical interactions between cells can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared via phagocytosis, with defects associated with a variety of diseases. How cell-cell physical associations affect programmed cell elimination is not fully understood. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance. We previously described the specialized cell death program \"Compartmentalized Cell Elimination\" (CCE) in the C. elegans embryo. During CCE, the tail-spike scaffolding cell (TSC), a polarized epithelial cell with a posteriorly-directed process, is eliminated via an ordered death sequence. The TSC scaffolds the tail tip, formed by the hyp10 epithelial cell, which in turn serves as the phagocyte for the dying TSC process. We have previously provided mechanistic insights into the poorly understood step of phagocytosis, phagosome sealing, reporting that the fusogen EFF-1 helps clear the TSC process specifically. We identify here a genetic pathway that promotes the translocation of EFF-1 to sealing sites. We identify an upstream role for cell-cell physical association and signaling via the cadherin CDH-3, followed by new roles for the transcription factors YAP-1/YAP and EGL-44/TEAD in promoting the localization of SYX-2/Syntaxin around the dying TSC remnant. Moreover, we find that SYX-2, known to promote EFF-1's role in wound healing, also promotes EFF-1 translocation to sites of phagosome closure. Our work sheds additional light on phagosome sealing and implicates cell-cell adhesive forces and signaling as important in cell uptake.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosomal translocations are a significant driver of hybrid sterility in rice. 染色体易位是水稻杂交不育的重要驱动因素。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf126

Zhenwei Xie, Hai Zheng, Siqi Cheng, Hao Yu, Xiaowen Yu, Chaolong Wang, Jian Wang, Bowen Yao, Xiaokang Jiang, Yang Hu, Anqi Jian, Xiaodong He, Junwen Gao, Minrui Chen, Yun Chen, Yuantao Zhu, Yulong Ren, Zhijun Cheng, Cailin Lei, Qibing Lin, Xin Wang, Xiuping Guo, Yunlu Tian, Shijia Liu, Xi Liu, Ling Jiang, Chuanyin Wu, Shanshan Zhu, Zhigang Zhao, Jianmin Wan

{"title":"Chromosomal translocations are a significant driver of hybrid sterility in rice.","authors":"Zhenwei Xie, Hai Zheng, Siqi Cheng, Hao Yu, Xiaowen Yu, Chaolong Wang, Jian Wang, Bowen Yao, Xiaokang Jiang, Yang Hu, Anqi Jian, Xiaodong He, Junwen Gao, Minrui Chen, Yun Chen, Yuantao Zhu, Yulong Ren, Zhijun Cheng, Cailin Lei, Qibing Lin, Xin Wang, Xiuping Guo, Yunlu Tian, Shijia Liu, Xi Liu, Ling Jiang, Chuanyin Wu, Shanshan Zhu, Zhigang Zhao, Jianmin Wan","doi":"10.1093/genetics/iyaf126","DOIUrl":"10.1093/genetics/iyaf126","url":null,"abstract":"Hybrid sterility is a major barrier in exploiting hybrid vigor in rice grains produced by crossing distantly related parents. While genetic mechanisms such as the killer-protector system have been extensively studied, novel systems underlying hybrid sterility remain poorly characterized. Here, a novel hybrid sterility system governed by two tightly pseudolinked loci SGA1 (on chromosome 1) and SGA2 (on chromosome 2) is reported, which induces semi-sterility in male and female gametes during hybridization between the indica and japonica subspecies. Chromosomal translocations were proposed as the basis for pseudolinkage and unbiased segregation, supported by cytological evidence of meiotic quadrivalent configurations and translocation breakpoint sequences. Gametophytic sterility was identified as the primary driver of dual male-female semi-sterility in translocated heterozygotes. Furthermore, large-segment chromosomal translocations are found to be widespread in rice. Analysis of 120 pangenomic rice accessions revealed that chromosomal translocations are prevalent among cultivars, with one-third exhibiting large translocations (>500 kb). Translocation breakpoints were mainly localized in intergenic and intronic regions, and the disrupted genes were identified as predominantly transposons and retrotransposons. Besides, large translocations were validated through sequence analysis and phenotypic assays. Overall, this study establishes chromosomal translocations as a critical driver of hybrid sterility and provides new insights into heterosis constraints.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates. AMPK改变蛋白酶体磷酸化状态，防止蛋白酶体持续凝聚。

IF 5.1 3区生物学

Genetics Pub Date : 2025-08-29 DOI: 10.1093/genetics/iyaf179

Jianhui Li, Conner Butcher, Kyle VanderVen, Meredith Fitz-Enz, Mark Hochstrasser

{"title":"AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates.","authors":"Jianhui Li, Conner Butcher, Kyle VanderVen, Meredith Fitz-Enz, Mark Hochstrasser","doi":"10.1093/genetics/iyaf179","DOIUrl":"10.1093/genetics/iyaf179","url":null,"abstract":"Proteasomes are large multiprotein complexes required for selective intracellular protein degradation, regulating numerous cellular processes and maintaining protein homeostasis and organismal health. In the budding yeast Saccharomyces cerevisiae grown under different glucose conditions, proteasomes undergo dynamic phase transitions between free and condensate states concomitant with nucleocytoplasmic translocation. Low glucose-induced cytoplasmic proteasome condensates are usually reversible but become persistent in the absence of AMP-activated protein kinase (AMPK). AMPK is important for proteasome condensate dissolution and proteasome nuclear reimport upon glucose refeeding of quiescent cells. Here we found that AMPK activities and the AMPK signaling pathway affect proteasome subunit phosphorylation, which correlates with the solubility and reversibility of proteasome condensates. Nuclear and cytoplasmic AMPK functions redundantly in proteasome condensate dissolution. AMPK interacts with the proteasome regulatory particle in an AMPK activity-independent manner. At least 50 kinases and phosphatases have been found to associate with the AMPK complex. Therefore, the prevention of persistent proteasome condensate formation by AMPK likely results from regulating the antagonistic effects of downstream kinases and phosphatases on proteasome phosphorylation. A mechanistic understanding of the downstream effector proteins of AMPK that directly regulate proteasome subunit phosphorylation will provide insights into how proteasome phosphorylation is linked to proteasome condensate regulation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0