Genetics最新文献_第9页

Neuronal postdevelopmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in Caenorhabditis elegans. 神经元发育后作用的SAX-7S/L1CAM可以作为裂解片段维持秀丽隐杆线虫的神经元结构。

IF 3.3 3区生物学

Genetics Pub Date : 2021-08-09 DOI: 10.1093/genetics/iyab086

Virginie E Desse, Cassandra R Blanchette, Malika Nadour, Paola Perrat, Lise Rivollet, Anagha Khandekar, Claire Y Bénard

{"title":"Neuronal postdevelopmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in Caenorhabditis elegans.","authors":"Virginie E Desse, Cassandra R Blanchette, Malika Nadour, Paola Perrat, Lise Rivollet, Anagha Khandekar, Claire Y Bénard","doi":"10.1093/genetics/iyab086","DOIUrl":"https://doi.org/10.1093/genetics/iyab086","url":null,"abstract":"Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal's growth, maturation processes, the addition of new neurons, body movements, and aging. The Caenorhabditis elegans protein SAX-7, homologous to the vertebrate L1 protein family of neural adhesion molecules, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by postdevelopmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants' neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance and may help decipher processes that go awry in some neurodegenerative conditions.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883803/pdf/iyab086.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39085019","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: 2

Parallel and population-specific gene regulatory evolution in cold-adapted fly populations. 冷适应蝇种群的平行和种群特异性基因调控进化。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab077

Yuheng Huang, Justin B Lack, Grant T Hoppel, John E Pool

{"title":"Parallel and population-specific gene regulatory evolution in cold-adapted fly populations.","authors":"Yuheng Huang, Justin B Lack, Grant T Hoppel, John E Pool","doi":"10.1093/genetics/iyab077","DOIUrl":"https://doi.org/10.1093/genetics/iyab077","url":null,"abstract":"Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The cold-adapted populations were known to show population genetic evidence for parallel evolution at the SNP level, and here we find evidence for parallel expression evolution between them, with stronger parallelism at larval and adult stages than for pupae. We also implement a flexible method to estimate cis- vs trans-encoded contributions to expression or splicing differences at the adult stage. The apparent contributions of cis- vs trans-regulation to adaptive evolution vary substantially among population pairs. While two of three population pairs show a greater enrichment of cis-regulatory differences among adaptation candidates, trans-regulatory differences are more likely to be implicated in parallel expression changes between population pairs. Genes with significant cis-effects are enriched for signals of elevated genetic differentiation between cold- and warm-adapted populations, suggesting that they are potential targets of local adaptation. These findings expand our knowledge of adaptive gene regulatory evolution and our ability to make inferences about this important and widespread process.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38982513","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: 8

Population dynamics of GC-changing mutations in humans and great apes. 人类和类人猿中gc改变突变的种群动态。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab083

Juraj Bergman, Mikkel Heide Schierup

{"title":"Population dynamics of GC-changing mutations in humans and great apes.","authors":"Juraj Bergman, Mikkel Heide Schierup","doi":"10.1093/genetics/iyab083","DOIUrl":"https://doi.org/10.1093/genetics/iyab083","url":null,"abstract":"The nucleotide composition of the genome is a balance between the origin and fixation rates of different mutations. For example, it is well-known that transitions occur more frequently than transversions, particularly at CpG sites. Differences in fixation rates of mutation types are less explored. Specifically, recombination-associated GC-biased gene conversion (gBGC) may differentially impact GC-changing mutations, due to differences in their genomic distributions and efficiency of mismatch repair mechanisms. Given that recombination evolves rapidly across species, we explore gBGC of different mutation types across human populations and great ape species. We report a stronger correlation between segregating GC frequency and recombination for transitions than for transversions. Notably, CpG transitions are most strongly affected by gBGC in humans and chimpanzees. We show that the overall strength of gBGC is generally correlated with effective population sizes in humans, with some notable exceptions, such as a stronger effect of gBGC on non-CpG transitions in populations of European descent. Furthermore, species of the Gorilla and Pongo genus have a greatly reduced gBGC effect on CpG sites. We also study the dependence of gBGC dynamics on flanking nucleotides and show that some mutation types evolve in opposition to the gBGC expectation, likely due to the hypermutability of specific nucleotide contexts. Our results highlight the importance of different gBGC dynamics experienced by GC-changing mutations and their impact on nucleotide composition evolution.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335939/pdf/iyab083.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38988304","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: 2

Rapid detection of inter-clade recombination in SARS-CoV-2 with Bolotie. 利用 Bolotie 快速检测 SARS-CoV-2 中的支系间重组。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab074

Ales Varabyou, Christopher Pockrandt, Steven L Salzberg, Mihaela Pertea

引用次数: 0

Environmentally contingent control of Candida albicans cell wall integrity by transcriptional regulator Cup9. 转录调节因子 Cup9 对白色念珠菌细胞壁完整性的环境控制。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab075

Yuichi Ichikawa, Vincent M Bruno, Carol A Woolford, Hannah Kim, Eunsoo Do, Grace C Brewer, Aaron P Mitchell

{"title":"Environmentally contingent control of Candida albicans cell wall integrity by transcriptional regulator Cup9.","authors":"Yuichi Ichikawa, Vincent M Bruno, Carol A Woolford, Hannah Kim, Eunsoo Do, Grace C Brewer, Aaron P Mitchell","doi":"10.1093/genetics/iyab075","DOIUrl":"10.1093/genetics/iyab075","url":null,"abstract":"The fungal pathogen Candida albicans is surrounded by a cell wall that is the target of caspofungin and other echinocandin antifungals. Candida albicans can grow in several morphological forms, notably budding yeast and hyphae. Yeast and hyphal forms differ in cell wall composition, leading us to hypothesize that there may be distinct genes required for yeast and hyphal responses to caspofungin. Mutants in 27 genes reported previously to be caspofungin hypersensitive under yeast growth conditions were all caspofungin hypersensitive under hyphal growth conditions as well. However, a screen of mutants defective in transcription factor genes revealed that Cup9 is required for normal caspofungin tolerance under hyphal and not yeast growth conditions. In a hyphal-defective efg1Δ/Δ background, Cup9 is still required for normal caspofungin tolerance. This result argues that Cup9 function is related to growth conditions rather than cell morphology. RNA-seq conducted under hyphal growth conditions indicated that 361 genes were up-regulated and 145 genes were down-regulated in response to caspofungin treatment. Both classes of caspofungin-responsive genes were enriched for cell wall-related proteins, as expected for a response to disruption of cell wall integrity and biosynthesis. The cup9Δ/Δ mutant, treated with caspofungin, had reduced RNA levels of 40 caspofungin up-regulated genes, and had increased RNA levels of 8 caspofungin down-regulated genes, an indication that Cup9 has a narrow rather than global role in the cell wall integrity response. Five Cup9-activated surface-protein genes have roles in cell wall integrity, based on mutant analysis published previously (PGA31 and IFF11) or shown here (ORF19.3499, ORF19.851, or PGA28), and therefore may explain the hypersensitivity of the cup9Δ/Δmutant to caspofungin. Our findings define Cup9 as a new determinant of caspofungin susceptibility.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864738/pdf/iyab075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38983054","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

In vivo tissue-specific chromatin profiling in Drosophila melanogaster using GFP-tagged nuclei. 使用gfp标记的细胞核对黑腹果蝇进行体内组织特异性染色质分析。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab079

Juan Jauregui-Lozano, Kimaya Bakhle, Vikki M Weake

{"title":"In vivo tissue-specific chromatin profiling in Drosophila melanogaster using GFP-tagged nuclei.","authors":"Juan Jauregui-Lozano, Kimaya Bakhle, Vikki M Weake","doi":"10.1093/genetics/iyab079","DOIUrl":"https://doi.org/10.1093/genetics/iyab079","url":null,"abstract":"The chromatin landscape defines cellular identity in multicellular organisms with unique patterns of DNA accessibility and histone marks decorating the genome of each cell type. Thus, profiling the chromatin state of different cell types in an intact organism under disease or physiological conditions can provide insight into how chromatin regulates cell homeostasis in vivo. To overcome the many challenges associated with characterizing chromatin state in specific cell types, we developed an improved approach to isolate Drosophila melanogaster nuclei tagged with a GFPKASH protein. The perinuclear space-localized KASH domain anchors GFP to the outer nuclear membrane, and expression of UAS-GFPKASH can be controlled by tissue-specific Gal4 drivers. Using this protocol, we profiled chromatin accessibility using an improved version of Assay for Transposable Accessible Chromatin followed by sequencing (ATAC-seq), called Omni-ATAC. In addition, we examined the distribution of histone marks using Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and Cleavage Under Targets and Tagmentation (CUT&Tag) in adult photoreceptor neurons. We show that the chromatin landscape of photoreceptors reflects the transcriptional state of these cells, demonstrating the quality and reproducibility of our approach for profiling the transcriptome and epigenome of specific cell types in Drosophila.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864739/pdf/iyab079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39008024","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

Proof of principle for piggyBac-mediated transgenesis in the flatworm Macrostomum lignano. piggybach介导扁形虫巨口木脂虫转基因的原理证明。

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-14 DOI: 10.1093/genetics/iyab076

Kirill Ustyantsev, Jakub Wudarski, Igor Sukhikh, Filipa Reinoite, Stijn Mouton, Eugene Berezikov

引用次数: 0

Causes of variability in estimates of mutational variance from mutation accumulation experiments 突变积累实验中突变方差估计的变异原因

IF 3.3 3区生物学

Genetics Pub Date : 2021-07-09 DOI: 10.1093/genetics/iyac060

C. Conradsen, M. Blows, K. McGuigan

{"title":"Causes of variability in estimates of mutational variance from mutation accumulation experiments","authors":"C. Conradsen, M. Blows, K. McGuigan","doi":"10.1093/genetics/iyac060","DOIUrl":"https://doi.org/10.1093/genetics/iyac060","url":null,"abstract":"Characteristics of the new phenotypic variation introduced via mutation have broad implications in evolutionary and medical genetics. Standardised estimates of this mutational variance, VM, span two orders of magnitude, but the causes of this remain poorly resolved. We investigated estimate heterogeneity using two approaches. First, meta-analyses of ~150 estimates from 37 mutation accumulation (MA) studies did not support a difference among taxa (which differ in mutation rate) in standardised VM, but provided equivocal support for standardised VM to vary with trait type (life history versus morphology, predicted to differ in mutation rate). Notably, several experimental factors were confounded with taxon and trait, and further empirical data are required to resolve their influences. Second, we analysed morphological data from an experiment in Drosophila serrata to determine the potential for unintentional heterogeneity among environments in which phenotypes were measured (i.e., among laboratories or time points) or transient segregation of mutations within MA lines to affect standardised VM. Approximating the size of an average MA experiment, variability among repeated estimates of (accumulated) mutational variance was comparable to variation among published estimates of standardised VM for morphological traits. This heterogeneity was (partially) attributable to unintended environmental variation or within line segregation of mutations only for wing size, not wing shape traits. We conclude that sampling error contributed substantial variation within this experiment, and infer that it will also contribute substantially to differences among published estimates. We suggest a logistically permissive approach to improve the precision of estimates, and consequently our understanding of the dynamics of mutational variance of quantitative traits.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"221 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42146454","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: 2

Transposon-induced inversions activate gene expression in the maize pericarp. 转座子诱导的逆转录激活玉米果皮中的基因表达。

IF 3.3 3区生物学

Genetics Pub Date : 2021-06-24 DOI: 10.1093/genetics/iyab062

Sharu Paul Sharma, Tao Zuo, Thomas Peterson

引用次数: 3

Catalase inhibition by nitric oxide potentiates hydrogen peroxide to trigger catastrophic chromosome fragmentation in Escherichia coli. 过氧化氢酶抑制一氧化氮增强过氧化氢触发大肠杆菌灾难性染色体断裂。

IF 3.3 3区生物学

Genetics Pub Date : 2021-06-24 DOI: 10.1093/genetics/iyab057

Pooja Agashe, Andrei Kuzminov

{"title":"Catalase inhibition by nitric oxide potentiates hydrogen peroxide to trigger catastrophic chromosome fragmentation in Escherichia coli.","authors":"Pooja Agashe, Andrei Kuzminov","doi":"10.1093/genetics/iyab057","DOIUrl":"https://doi.org/10.1093/genetics/iyab057","url":null,"abstract":"Hydrogen peroxide (H2O2, HP) is a universal toxin that organisms deploy to kill competing or invading cells. Bactericidal action of H2O2 presents several questions. First, the lethal H2O2 concentrations in bacterial cultures are 1000x higher than, for example, those calculated for the phagosome. Second, H2O2-alone kills bacteria in cultures either by mode-one, via iron-mediated chromosomal damage, or by mode-two, via unknown targets, but the killing mode in phagosomes is unclear. Third, phagosomal H2O2 toxicity is enhanced by production of nitric oxide (NO), but in vitro studies disagree: some show NO synergy with H2O2 antimicrobial action, others instead report alleviation. To investigate this \"NO paradox,\" we treated Escherichia coli with various concentrations of H2O2-alone or H2O2+NO, measuring survival and chromosome stability. We found that all NO concentrations make sublethal H2O2 treatments highly lethal, via triggering catastrophic chromosome fragmentation (mode-one killing). Yet, NO-alone is not lethal, potentiating H2O2 toxicity by blocking H2O2 scavenging in cultures. Catalases represent obvious targets of NO inhibition, and catalase-deficient mutants are indeed killed equally by H2O2-alone or H2O2+NO treatments, also showing similar levels of chromosome fragmentation. Interestingly, iron chelation blocks chromosome fragmentation in catalase-deficient mutants without blocking H2O2-alone lethality, indicating mode-two killing. In fact, mode-two killing of WT cells by much higher H2O2 concentrations is transiently alleviated by NO, reproducing the \"NO paradox.\" We conclude that NO potentiates H2O2 toxicity by promoting mode-one killing (via catastrophic chromosome fragmentation) by otherwise static low H2O2 concentrations, while transiently suppressing mode-two killing by immediately lethal high H2O2 concentrations.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"218 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225348/pdf/iyab057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010623","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: 4