Genetics最新文献_第10页

Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor. 念珠菌 Pdr1 转录因子的转录激活需要重叠的辅激活因子功能。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae115

Thomas P Conway, Lucia Simonicova, W Scott Moye-Rowley

{"title":"Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor.","authors":"Thomas P Conway, Lucia Simonicova, W Scott Moye-Rowley","doi":"10.1093/genetics/iyae115","DOIUrl":"10.1093/genetics/iyae115","url":null,"abstract":"Azole resistance in the pathogenic yeast Candida glabrata is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene CDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive PDR1 alleles. While the identity of hyperactive PDR1 alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and 2 different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and 2 different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either SNF2 or SPT7 exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect in PDR1 autoregulation, revealing that these complexes work together to ensure high-level Pdr1-dependent gene transcription.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727968","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

Chk2 homolog Mek1 limits exonuclease 1-dependent DNA end resection during meiotic recombination in Saccharomyces cerevisiae. Chk2 同源物 Mek1 限制了 S. cerevisiae 中减数分裂重组过程中 Exo1 依赖性 DNA 末端切除。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae112

Jennifer T Krystosek, Douglas K Bishop

引用次数: 0

Tetraploid interspecific hybrids between Asian and African rice species restore fertility depending on killer-protector loci for hybrid sterility. 亚洲和非洲水稻物种间的四倍体种间杂交种依靠杂交不育的杀手保护基因座恢复生育能力。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae104

Daichi Kuniyoshi, Megumi Ishihara, Koichi Yamamori, Yohei Koide, Yuji Kishima

{"title":"Tetraploid interspecific hybrids between Asian and African rice species restore fertility depending on killer-protector loci for hybrid sterility.","authors":"Daichi Kuniyoshi, Megumi Ishihara, Koichi Yamamori, Yohei Koide, Yuji Kishima","doi":"10.1093/genetics/iyae104","DOIUrl":"10.1093/genetics/iyae104","url":null,"abstract":"Interspecific F1 hybrids between Asian (Oryza sativa) and African rice (Oryza glaberrima) exhibit severe sterility caused by the accumulation of hybrid sterility genes/loci at 15 or more loci. The mechanisms underlying the hybrid sterility genes are largely unknown; however, a few genes associated with the killer-protector system, which is the system most frequently associated with hybrid sterility genes, have been identified. We previously produced fertile plants as tetraploids derived from diploid interspecific F1 hybrids through anther culture; therefore, it was suggested that hybrid sterility could be overcome following tetraploidization. We investigated whether tetraploid interspecific plants produced by crossing are fertile and tested the involvement of hybrid sterility genes in the process. Fertile tetraploid interspecific F1 hybrid plants were obtained by crossing 2 tetraploids of O. sativa and O. glaberrima. To elucidate the relationships between pollen fertility and the hybrid sterility loci in the tetraploid F1 microspores, we performed genetic analyses of the tetraploid F2 hybrids and diploid plants obtained from the microspores of tetraploid interspecific hybrids by anther culture. The result suggested that the tetraploid interspecific hybrids overcame pollen and seed infertility based on the proportion of loci with the killer-protector system present in the tetraploids. The heterozygous hybrid sterility loci with the killer-protector system in the tetraploid segregate the homozygous killed allele (16.7-21.4%), with more than three-quarters of the gametes surviving. We theoretically and experimentally demonstrated that fertile rice progenies can be grown from tetraploid interspecific hybrids.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471823","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

An acidic loop in the forkhead-associated domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates. 酵母减数分裂特异性激酶 Mek1 的 FHA 结构域中的一个酸性环与 Mek1 底物亚群中的一个特定图案相互作用。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae106

Qixuan Weng, Lihong Wan, Geburah C Straker, Tom D Deegan, Bernard P Duncker, Aaron M Neiman, Ed Luk, Nancy M Hollingsworth

{"title":"An acidic loop in the forkhead-associated domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates.","authors":"Qixuan Weng, Lihong Wan, Geburah C Straker, Tom D Deegan, Bernard P Duncker, Aaron M Neiman, Ed Luk, Nancy M Hollingsworth","doi":"10.1093/genetics/iyae106","DOIUrl":"10.1093/genetics/iyae106","url":null,"abstract":"The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at double-strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover-specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a 5-amino acid sequence, RPSKR, located between the DNA-binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full-length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a noncanonical interaction with this motif. A second protein, the 5'-3' helicase Rrm3, similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in the MEK1 acidic loop validated the AlphaFold model, in that they specifically disrupt 2-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint and, in certain circumstances, exhibit more severe phenotypes compared to the NDT80 mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560154","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

Testing times: disentangling admixture histories in recent and complex demographies using ancient DNA. 测试时代：利用古 DNA 分解新近人口和复杂人口的混血历史。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae110

Matthew P Williams, Pavel Flegontov, Robert Maier, Christian D Huber

{"title":"Testing times: disentangling admixture histories in recent and complex demographies using ancient DNA.","authors":"Matthew P Williams, Pavel Flegontov, Robert Maier, Christian D Huber","doi":"10.1093/genetics/iyae110","DOIUrl":"10.1093/genetics/iyae110","url":null,"abstract":"Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches-firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes-and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P-values and f3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f-statistic estimations.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141628040","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

Origin and maintenance of large ribosomal RNA gene repeat size in mammals. 哺乳动物中大核糖体 RNA 基因重复大小的起源和维持。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae121

Emma Macdonald, Annabel Whibley, Paul D Waters, Hardip Patel, Richard J Edwards, Austen R D Ganley

{"title":"Origin and maintenance of large ribosomal RNA gene repeat size in mammals.","authors":"Emma Macdonald, Annabel Whibley, Paul D Waters, Hardip Patel, Richard J Edwards, Austen R D Ganley","doi":"10.1093/genetics/iyae121","DOIUrl":"10.1093/genetics/iyae121","url":null,"abstract":"The genes encoding ribosomal RNA are highly conserved across life and in almost all eukaryotes are present in large tandem repeat arrays called the rDNA. rDNA repeat unit size is conserved across most eukaryotes but has expanded dramatically in mammals, principally through the expansion of the intergenic spacer region that separates adjacent rRNA coding regions. Here, we used long-read sequence data from representatives of the major amniote lineages to determine where in amniote evolution rDNA unit size increased. We find that amniote rDNA unit sizes fall into two narrow size classes: \"normal\" (∼11-20 kb) in all amniotes except monotreme, marsupial, and eutherian mammals, which have \"large\" (∼35-45 kb) sizes. We confirm that increases in intergenic spacer length explain much of this mammalian size increase. However, in stark contrast to the uniformity of mammalian rDNA unit size, mammalian intergenic spacers differ greatly in sequence. These results suggest a large increase in intergenic spacer size occurred in a mammalian ancestor and has been maintained despite substantial sequence changes over the course of mammalian evolution. This points to a previously unrecognized constraint on the length of the intergenic spacer, a region that was thought to be largely neutral. We finish by speculating on possible causes of this constraint.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753075","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

Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae. 在酿酒酵母中，Mck1 介导的 CENP-A 蛋白水解可防止 CENP-A 误定位，从而提高染色体稳定性。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae108

Tianyi Zhang, Wei-Chun Au, Kentaro Ohkuni, Roshan L Shrestha, Peter Kaiser, Munira A Basrai

{"title":"Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae.","authors":"Tianyi Zhang, Wei-Chun Au, Kentaro Ohkuni, Roshan L Shrestha, Peter Kaiser, Munira A Basrai","doi":"10.1093/genetics/iyae108","DOIUrl":"10.1093/genetics/iyae108","url":null,"abstract":"Centromeric localization of evolutionarily conserved CENP-A (Cse4 in Saccharomyces cerevisiae) is essential for chromosomal stability. Mislocalization of overexpressed CENP-A to noncentromeric regions contributes to chromosomal instability in yeasts, flies, and humans. Overexpression and mislocalization of CENP-A observed in many cancers are associated with poor prognosis. Previous studies have shown that F-box proteins, Cdc4 and Met30 of the Skp, Cullin, F-box ubiquitin ligase cooperatively regulate proteolysis of Cse4 to prevent Cse4 mislocalization and chromosomal instability under normal physiological conditions. Mck1-mediated phosphorylation of Skp, Cullin, F-box-Cdc4 substrates such as Cdc6 and Rcn1 enhances the interaction of the substrates with Cdc4. Here, we report that Mck1 interacts with Cse4, and Mck1-mediated proteolysis of Cse4 prevents Cse4 mislocalization for chromosomal stability. Our results showed that mck1Δ strain overexpressing CSE4 (GAL-CSE4) exhibits lethality, defects in ubiquitin-mediated proteolysis of Cse4, mislocalization of Cse4, and reduced Cse4-Cdc4 interaction. Strain expressing GAL-cse4-3A with mutations in three potential Mck1 phosphorylation consensus sites (S10, S16, and T166) also exhibits growth defects, increased stability with mislocalization of Cse4-3A, chromosomal instability, and reduced interaction with Cdc4. Constitutive expression of histone H3 (Δ16H3) suppresses the chromosomal instability phenotype of GAL-cse4-3A strain, suggesting that the chromosomal instability phenotype is linked to Cse4-3A mislocalization. We conclude that Mck1 and its three potential phosphorylation sites on Cse4 promote Cse4-Cdc4 interaction and this contributes to ubiquitin-mediated proteolysis of Cse4 preventing its mislocalization and chromosomal instability. These studies advance our understanding of pathways that regulate cellular levels of CENP-A to prevent mislocalization of CENP-A in human cancers.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564919","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

Conditional nmy-1 and nmy-2 alleles establish that nonmuscle myosins are required for late Caenorhabditis elegans embryonic elongation. 条件性 nmy-1 和 nmy-2 等位基因证实，非肌肉肌球蛋白是秀丽隐杆线虫胚胎后期伸长所必需的。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae109

Kelly Molnar, Shashi Kumar Suman, Jeanne Eichelbrenner, Camille N Plancke, François B Robin, Michel Labouesse

{"title":"Conditional nmy-1 and nmy-2 alleles establish that nonmuscle myosins are required for late Caenorhabditis elegans embryonic elongation.","authors":"Kelly Molnar, Shashi Kumar Suman, Jeanne Eichelbrenner, Camille N Plancke, François B Robin, Michel Labouesse","doi":"10.1093/genetics/iyae109","DOIUrl":"10.1093/genetics/iyae109","url":null,"abstract":"The elongation of Caenorhabditis elegans embryos allows examination of mechanical interactions between adjacent tissues. Muscle contractions during late elongation induce the remodeling of epidermal circumferential actin filaments through mechanotransduction. Force inputs from the muscles deform circumferential epidermal actin filament, which causes them to be severed, eventually reformed, and shortened. This squeezing force drives embryonic elongation. We investigated the possible role of the nonmuscle myosins NMY-1 and NMY-2 in this process using nmy-1 and nmy-2 thermosensitive alleles. Our findings show these myosins act redundantly in late elongation, since double nmy-2(ts); nmy-1(ts) mutants immediately stop elongation when raised to 25°C. Their inactivation does not reduce muscle activity, as measured from epidermis deformation, suggesting that they are directly involved in the multistep process of epidermal remodeling. Furthermore, NMY-1 and NMY-2 inactivation is reversible when embryos are kept at the nonpermissive temperature for a few hours. However, after longer exposure to 25°C double mutant embryos fail to resume elongation, presumably because NMY-1 was seen to form protein aggregates. We propose that the two C. elegans nonmuscle myosin II act during actin remodeling either to bring severed ends or hold them.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761973","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

Behavioral plasticity. 行为可塑性

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae105

Yun Zhang, Yuichi Iino, William R Schafer

引用次数: 0

Impacts of pleiotropy and migration on repeated genetic adaptation. 多效性和迁移对重复遗传适应的影响。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae111

Paul Battlay, Sam Yeaman, Kathryn A Hodgins

{"title":"Impacts of pleiotropy and migration on repeated genetic adaptation.","authors":"Paul Battlay, Sam Yeaman, Kathryn A Hodgins","doi":"10.1093/genetics/iyae111","DOIUrl":"10.1093/genetics/iyae111","url":null,"abstract":"Observations of genetically repeated evolution (repeatability) in complex organisms are incongruent with the Fisher-Orr model, which implies that repeated use of the same gene should be rare when mutations are pleiotropic (i.e. affect multiple traits). When spatially divergent selection occurs in the presence of migration, mutations of large effect are more strongly favored, and hence, repeatability is more likely, but it is unclear whether this observation is limited by pleiotropy. Here, we explore this question using individual-based simulations of a two-patch model incorporating multiple quantitative traits governed by mutations with pleiotropic effects. We explore the relationship between fitness trade-offs and repeatability by varying the alignment between mutation effect and spatial variation in trait optima. While repeatability decreases with increasing trait dimensionality, trade-offs in mutation effects on traits do not strongly limit the contribution of a locus of large effect to repeated adaptation, particularly under increased migration. These results suggest that repeatability will be more pronounced for local rather than global adaptation. Whereas pleiotropy limits repeatability in a single-population model, when there is local adaptation with gene flow, repeatability can occur if some loci are able to produce alleles of large effect, even when there are pleiotropic trade-offs.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601987","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