Genetics最新文献

{"title":"Identification of factors limiting the allotopic production of the Cox2 subunit of yeast cytochrome c oxidase.","authors":"Felipe Nieto-Panqueva, Miriam Vázquez-Acevedo, Patrice P Hamel, Diego González-Halphen","doi":"10.1093/genetics/iyae058","DOIUrl":"https://doi.org/10.1093/genetics/iyae058","url":null,"abstract":"Mitochondrial genes can be naturally or artificially relocalized in the nuclear genome in a process known as allotopic expression, such is the case of the mitochondrial cox2 gene, encoding subunit II of cytochrome c oxidase (CcO). In yeast, cox2 can be allotopically expressed and is able to restore respiratory growth of a cox2-null mutant if the Cox2 subunit carries the W56R substitution within the first transmembrane stretch. However, the COX2W56R strain exhibits reduced growth rates and lower steady-state CcO levels when compared to wild-type yeast. Here, we investigated the impact of overexpressing selected candidate genes predicted to enhance internalization of the allotopic Cox2W56R precursor into mitochondria. The overproduction of Cox20, Oxa1, and Pse1 facilitated Cox2W56R precursor internalization, improving the respiratory growth of the COX2W56R strain. Overproducing TIM22 components had a limited effect on Cox2W56R import, while overproducing TIM23-related components showed a negative effect. We further explored the role of the Mgr2 subunit within the TIM23 translocator in the import process by deleting and overexpressing the MGR2 gene. Our findings indicate that Mgr2 is instrumental in modulating the TIM23 translocon to correctly sort Cox2W56R. We propose a biogenesis pathway followed by the allotopically produced Cox2 subunit based on the participation of the two different structural/functional forms of the TIM23 translocon, TIM23MOTOR and TIM23SORT, that must follow a concerted and sequential mode of action to insert Cox2W56R into the inner mitochondrial membrane in the correct Nout-Cout topology.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"104 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612309","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}

{"title":"Harnessing the power of new genetic tools to illuminate Giardia biology and pathogenesis.","authors":"Kari D Hagen, Christopher J S Hart, Shane G McInally, Scott C Dawson","doi":"10.1093/genetics/iyae038","DOIUrl":"https://doi.org/10.1093/genetics/iyae038","url":null,"abstract":"Giardia is a prevalent single-celled microaerophilic intestinal parasite causing diarrheal disease and significantly impacting global health. Double diploid (essentially tetraploid) Giardia trophozoites have presented a formidable challenge to the development of molecular genetic tools to interrogate gene function. High sequence divergence and the high percentage of hypothetical proteins lacking homology to proteins in other eukaryotes have limited our understanding of Giardia protein function, slowing drug target validation and development. For more than 25 years, Giardia A and B assemblages have been readily amenable to transfection with plasmids or linear DNA templates. Here, we highlight the utility and power of genetic approaches developed to assess protein function in Giardia, with particular emphasis on the more recent clustered regularly interspaced palindromic repeats/Cas9-based methods for knockdowns and knockouts. Robust and reliable molecular genetic approaches are fundamental toward the interrogation of Giardia protein function and evaluation of druggable targets. New genetic approaches tailored for the double diploid Giardia are imperative for understanding Giardia's unique biology and pathogenesis.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"13 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612369","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}

{"title":"Quantitative proteomic analysis reveals unique Hsp90 cycle-dependent client interactions.","authors":"Erick I Rios, Davi Gonçalves, Kevin A Morano, Jill L Johnson","doi":"10.1093/genetics/iyae057","DOIUrl":"https://doi.org/10.1093/genetics/iyae057","url":null,"abstract":"Hsp90 is an abundant and essential molecular chaperone that mediates the folding and activation of client proteins in a nucleotide-dependent cycle. Hsp90 inhibition directly or indirectly impacts the function of 10-15% of all proteins due to degradation of client proteins or indirect downstream effects. Due to its role in chaperoning oncogenic proteins, Hsp90 is an important drug target. However, compounds that occupy the ATP-binding pocket and broadly inhibit function have not achieved widespread use due to negative effects. More selective inhibitors are needed; however, it is unclear how to achieve selective inhibition. We conducted a quantitative proteomic analysis of soluble proteins in yeast strains expressing wild-type Hsp90 or mutants that disrupt different steps in the client folding pathway. Out of 2,482 proteins in our sample set (approximately 38% of yeast proteins), we observed statistically significant changes in abundance of 350 (14%) of those proteins (log2 fold change ≥1.5). Of these, 257/350 (∼73%) with the strongest differences in abundance were previously connected to Hsp90 function. Principal component analysis of the entire dataset revealed that the effects of the mutants could be separated into three primary clusters. As evidence that Hsp90 mutants affect different pools of clients, simultaneous co-expression of two mutants in different clusters restored wild-type growth. Our data suggests that the ability of Hsp90 to sample a wide range of conformations allows the chaperone to mediate folding of a broad array of clients and that disruption of conformational flexibility results in client defects dependent on those states.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"162 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584210","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}

{"title":"UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.","authors":"Cody J Drozd, Tamjid A Chowdhury, Christopher C Quinn","doi":"10.1093/genetics/iyae053","DOIUrl":"https://doi.org/10.1093/genetics/iyae053","url":null,"abstract":"In humans, MAPK8IP3 (also known as JIP3) is a neurodevelopmental disorder-associated gene. In C. elegans, the UNC-16 ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"50 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583979","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}

{"title":"A Recql5 mutant facilitates complex CRISPR/Cas9-mediated-chromosomal engineering in mouse zygotes.","authors":"Satoru Iwata, Miki Nagahara, Risako Ido, Takashi Iwamoto","doi":"10.1093/genetics/iyae054","DOIUrl":"https://doi.org/10.1093/genetics/iyae054","url":null,"abstract":"Complex chromosomal rearrangements (CCRs) are often observed in clinical samples from patients with cancer and congenital diseases but are difficult to induce experimentally. Here, we report the first success in establishing animal models for CCRs. Mutation in Recql5, a crucial member of the DNA helicase RecQ family involved in DNA replication, transcription, and repair, enabled CRISPR/Cas9-mediated CCRs, establishing a mouse model containing triple fusion genes and megabase-sized inversions. Some of these structural features of individual chromosomal rearrangements use template switching and microhomology-mediated break-induced replication mechanisms and are reminiscent of the newly described phenomenon \"chromoanasynthesis.\" These data show that Recql5-mutant mice could be a powerful tool to analyze the pathogenesis of CCRs (particularly chromoanasynthesis) whose underlying mechanisms are poorly understood. The Recql5 mutants generated in this study are to be deposited at key animal research facilities, thereby making them accessible for future research on CCRs.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"121 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584421","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}

{"title":"The impact of differential transposition activities of autonomous and non-autonomous hAT transposable elements on genome architecture and gene expression in Caenorhabditis inopinata.","authors":"Ryuhei Hatanaka, Katsunori Tamagawa, Nami Haruta, Asako Sugimoto","doi":"10.1093/genetics/iyae052","DOIUrl":"https://doi.org/10.1093/genetics/iyae052","url":null,"abstract":"Transposable elements (TEs) are DNA sequences capable of moving within genomes and significantly influence genomic evolution. The nematode Caenorhabditis inopinata exhibits a much higher TE copy number than its sister species, C. elegans. In this study, we identified a novel autonomous TE belonging to the hAT superfamily from a spontaneous TE-insertion mutant in C. inopinata and named this transposon Ci-hAT1. Further bioinformatic analyses uncovered three additional autonomous hAT elements-Ci-hAT2, Ci-hAT3, and Ci-hAT4-along with over 1,000 copies of two non-autonomous miniature inverted-repeat transposable elements (MITEs), mCi-hAT1 and mCi-hAT4, likely derived from Ci-hAT1 and Ci-hAT4 through internal deletion. We tracked at least three sequential transpositions of Ci-hAT1 over several years. However, the transposition rates of the other three autonomous hAT elements were lower, suggesting varying activity levels. Notably, the distribution patterns of the two MITE families differed significantly: mCi-hAT1 was primarily located in the chromosome arms, a pattern observed in the TEs of other Caenorhabditis species, whereas mCi-hAT4 was more evenly distributed across chromosomes. Additionally, interspecific transcriptome analysis indicated that C. inopinata genes with upstream or intronic these MITE insertions tend to be more highly expressed than their orthologous genes in C. elegans. These findings highlight the significant role of de-silenced TEs in driving the evolution of genomes and transcriptomes, leading to species-specific genetic diversity.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"22 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584203","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}

{"title":"Enhanced pan-genomic resources at the maize genetics and genomics database.","authors":"Ethalinda K Cannon, John L Portwood, Rita K Hayford, Olivia C Haley, Jack M Gardiner, Carson M Andorf, Margaret R Woodhouse","doi":"10.1093/genetics/iyae036","DOIUrl":"https://doi.org/10.1093/genetics/iyae036","url":null,"abstract":"Pan-genomes, encompassing the entirety of genetic sequences found in a collection of genomes within a clade, are more useful than single reference genomes for studying species diversity. This is especially true for a species like Zea mays, which has a particularly diverse and complex genome. Presenting pan-genome data, analyses, and visualization is challenging, especially for a diverse species, but more so when pan-genomic data is linked to extensive gene model and gene data, including classical gene information, markers, insertions, expression and proteomic data, and protein structures as is the case at MaizeGDB. Here, we describe MaizeGDB's expansion to include the genic subset of the Zea pan-genome in a pan-gene data center featuring the maize genomes hosted at MaizeGDB, and the outgroup teosinte Zea genomes from the Pan-Andropoganeae project. The new data center offers a variety of browsing and visualization tools, including sequence alignment visualization, gene trees and other tools, to explore pan-genes in Zea that were calculated by the pipeline Pandagma. Combined, these data will help maize researchers study the complexity and diversity of Zea, and to use the comparative functions to validate pan-gene relationships for a selected gene model.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"14 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584404","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}

{"title":"WormBase 2024: status and transitioning to Alliance infrastructure.","authors":"Paul W Sternberg, Kimberly Van Auken, Qinghua Wang, Adam Wright, Karen Yook, Magdalena Zarowiecki, Valerio Arnaboldi, Andrés Becerra, Stephanie Brown, Scott Cain, Juancarlos Chan, Wen J Chen, Jaehyoung Cho, Paul Davis, Stavros Diamantakis, Sarah Dyer, Dionysis Grigoriadis, Christian A Grove, Todd Harris, Kevin Howe, Ranjana Kishore, Raymond Lee, Ian Longden, Manuel Luypaert, Hans-Michael Muller, Paulo Nuin, Mark Quinton-Tulloch, Daniela Raciti, Tim Schedl, Gary Schindelman, Lincoln Stein","doi":"10.1093/genetics/iyae050","DOIUrl":"https://doi.org/10.1093/genetics/iyae050","url":null,"abstract":"WormBase has been the major repository and knowledgebase of information about the genome and genetics of C. elegans and other nematodes of experimental interest for over two decades. We have three goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate key information from the literature and large-scale projects.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"51 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584214","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}

{"title":"Characterization of adaptation mechanisms in sorghum using a multireference back-cross nested association mapping design and envirotyping.","authors":"Vincent Garin, Chiaka Diallo, Mohamed Lamine Tékété, Korotimi Théra, Baptiste Guitton, Karim Dagno, Abdoulaye G Diallo, Mamoutou Kouressy, Willmar Leiser, Fred Rattunde, Ibrahima Sissoko, Aboubacar Touré, Baloua Nébié, Moussa Samaké, Jana Kholovà, Julien Frouin, David Pot, Michel Vaksmann, Eva Weltzien, Niaba Témé, Jean-François Rami","doi":"10.1093/genetics/iyae003","DOIUrl":"https://doi.org/10.1093/genetics/iyae003","url":null,"abstract":"Identifying the genetic factors impacting the adaptation of crops to environmental conditions is of key interest for conservation and selection purposes. It can be achieved using population genomics, and evolutionary or quantitative genetics. Here we present a sorghum multireference back-cross nested association mapping population composed of 3,901 lines produced by crossing 24 diverse parents to 3 elite parents from West and Central Africa-back-cross nested association mapping. The population was phenotyped in environments characterized by differences in photoperiod, rainfall pattern, temperature levels, and soil fertility. To integrate the multiparental and multi-environmental dimension of our data we proposed a new approach for quantitative trait loci (QTL) detection and parental effect estimation. We extended our model to estimate QTL effect sensitivity to environmental covariates, which facilitated the integration of envirotyping data. Our models allowed spatial projections of the QTL effects in agro-ecologies of interest. We utilized this strategy to analyze the genetic architecture of flowering time and plant height, which represents key adaptation mechanisms in environments like West Africa. Our results allowed a better characterization of well-known genomic regions influencing flowering time concerning their response to photoperiod with Ma6 and Ma1 being photoperiod-sensitive and the region of possible candidate gene Elf3 being photoperiod-insensitive. We also accessed a better understanding of plant height genetic determinism with the combined effects of phenology-dependent (Ma6) and independent (qHT7.1 and Dw3) genomic regions. Therefore, we argue that the West and Central Africa-back-cross nested association mapping and the presented analytical approach constitute unique resources to better understand adaptation in sorghum with direct application to develop climate-smart varieties.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"148 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918799","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}

{"title":"Premature endocycling of Drosophila follicle cells causes pleiotropic defects in oogenesis.","authors":"Hunter C Herriage, Brian R Calvi","doi":"10.1093/genetics/iyae009","DOIUrl":"https://doi.org/10.1093/genetics/iyae009","url":null,"abstract":"Endocycling cells grow and repeatedly duplicate their genome without dividing. Cells switch from mitotic cycles to endocycles in response to developmental signals during the growth of specific tissues in a wide range of organisms. The purpose of switching to endocycles, however, remains unclear in many tissues. Additionally, cells can switch to endocycles in response to conditional signals, which can have beneficial or pathological effects on tissues. However, the impact of these unscheduled endocycles on development is underexplored. Here, we use Drosophila ovarian somatic follicle cells as a model to examine the impact of unscheduled endocycles on tissue growth and function. Follicle cells normally switch to endocycles at mid-oogenesis. Inducing follicle cells to prematurely switch to endocycles resulted in lethality of the resulting embryos. Analysis of ovaries with premature follicle cell endocycles revealed aberrant follicular epithelial structure and pleiotropic defects in oocyte growth, developmental gene amplification, and the migration of a special set of follicle cells known as border cells. Overall, these findings reveal how unscheduled endocycles can disrupt tissue growth and function to cause aberrant development.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"5 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668899","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}