Genetics最新文献_第7页

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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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

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":null,"pages":null},"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

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":null,"pages":null},"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

Redesigning the Drosophila histone gene cluster: an improved genetic platform for spatiotemporal manipulation of histone function. 重新设计果蝇组蛋白基因簇：组蛋白功能时空操作的改良遗传平台

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae117

Aaron T Crain, Markus Nevil, Mary P Leatham-Jensen, Katherine B Reeves, A Gregory Matera, Daniel J McKay, Robert J Duronio

{"title":"Redesigning the Drosophila histone gene cluster: an improved genetic platform for spatiotemporal manipulation of histone function.","authors":"Aaron T Crain, Markus Nevil, Mary P Leatham-Jensen, Katherine B Reeves, A Gregory Matera, Daniel J McKay, Robert J Duronio","doi":"10.1093/genetics/iyae117","DOIUrl":"10.1093/genetics/iyae117","url":null,"abstract":"Mutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoans is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms were developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate the generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749379","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

A general and efficient representation of ancestral recombination graphs. 祖先重组图的通用高效表示法

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae100

Yan Wong, Anastasia Ignatieva, Jere Koskela, Gregor Gorjanc, Anthony W Wohns, Jerome Kelleher

引用次数: 0

The Drosophila tumor necrosis factor Eiger promotes Myc supercompetition independent of canonical Jun N-terminal kinase signaling. 果蝇 TNF Eiger 可促进 Myc 超级竞争，而不依赖于典型的 JNK 信号。

IF 3.3 3区生物学

Genetics Pub Date : 2024-09-04 DOI: 10.1093/genetics/iyae107

Albana L Kodra, Aditi Sharma Singh, Claire de la Cova, Marcello Ziosi, Laura A Johnston

{"title":"The Drosophila tumor necrosis factor Eiger promotes Myc supercompetition independent of canonical Jun N-terminal kinase signaling.","authors":"Albana L Kodra, Aditi Sharma Singh, Claire de la Cova, Marcello Ziosi, Laura A Johnston","doi":"10.1093/genetics/iyae107","DOIUrl":"10.1093/genetics/iyae107","url":null,"abstract":"Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process of cell selection in somatic tissues that is based on comparisons of cellular fitness. Here, we use a series of genetic tests in Drosophila to explore the relative contribution of the pleiotropic cytokine tumor necrosis factor α (TNFα) in Myc-mediated cell competition (also known as Myc supercompetition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNF receptor), and the adaptor proteins Traf4 and Traf6 are required to eliminate wild-type \"loser\" cells during Myc cell competition. Although typically the interaction between Egr and Grnd leads to cell death by activating the intracellular Jun N-terminal kinase (JNK) stress signaling pathway, our experiments reveal that many components of canonical JNK signaling are dispensable for cell death in Myc cell competition, including the JNKKK Tak1, the JNKK Hemipterous and the JNK Basket. Our results suggest that Egr/Grnd signaling participates in Myc cell competition but functions in a role that is largely independent of the JNK signaling pathway.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581293","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

Correction to: Genetics of Bacteria: a call for papers. Correction to：细菌遗传学：论文征集。

IF 3.3 3区生物学

Genetics Pub Date : 2024-08-20 DOI: 10.1093/genetics/iyae137

引用次数: 0