Genetics最新文献_第8页

Detecting deviations from Kingman coalescence using 2-site frequency spectra. 利用双向频谱检测金曼聚结的偏差。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf023

Eliot F Fenton, Daniel P Rice, John Novembre, Michael M Desai

{"title":"Detecting deviations from Kingman coalescence using 2-site frequency spectra.","authors":"Eliot F Fenton, Daniel P Rice, John Novembre, Michael M Desai","doi":"10.1093/genetics/iyaf023","DOIUrl":"10.1093/genetics/iyaf023","url":null,"abstract":"Demographic inference methods in population genetics typically assume that the ancestry of a sample can be modeled by the Kingman coalescent. A defining feature of this stochastic process is that it generates genealogies that are binary trees: no more than 2 ancestral lineages may coalesce at the same time. However, this assumption breaks down under several scenarios. For example, pervasive natural selection and extreme variation in offspring number can both generate genealogies with \"multiple-merger\" events in which more than 2 lineages coalesce instantaneously. Therefore, detecting violations of the Kingman assumptions (e.g. due to multiple mergers) is important both for understanding which forces have shaped the diversity of a population and for avoiding fitting misspecified models to data. Current methods to detect deviations from Kingman coalescence in genomic data rely primarily on the site frequency spectrum (SFS). However, the signatures of some non-Kingman processes (e.g. multiple mergers) in the SFS are also consistent with a Kingman coalescent with a time-varying population size. Here, we present a new statistical test for determining whether the Kingman coalescent with any population size history is consistent with population data. Our approach is based on information contained in the 2-site joint frequency spectrum (2-SFS) for pairs of linked sites, which has a different dependence on the topologies of genealogies than the SFS. Our statistical test is global in the sense that it can detect when the genome-wide genetic diversity is inconsistent with the Kingman model, rather than detecting outlier regions, as in selection scan methods. We validate this test using simulations and then apply it to demonstrate that genomic diversity data from Drosophila melanogaster is inconsistent with the Kingman coalescent.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371253","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 novel genome-wide association study method for detecting quantitative trait loci interacting with complex population structures in plant genetics. 植物遗传学中与复杂群体结构相互作用的数量性状位点的全基因组关联研究新方法。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf038

Kosuke Hamazaki, Hiroyoshi Iwata, Tristan Mary-Huard

{"title":"A novel genome-wide association study method for detecting quantitative trait loci interacting with complex population structures in plant genetics.","authors":"Kosuke Hamazaki, Hiroyoshi Iwata, Tristan Mary-Huard","doi":"10.1093/genetics/iyaf038","DOIUrl":"10.1093/genetics/iyaf038","url":null,"abstract":"In plant genetics, most modern association analyses are performed on panels that bring together individuals from several populations, including admixed individuals whose genomes comprise chromosomal regions from different populations. These panels can identify quantitative trait loci (QTLs) with population-specific effects and epistatic interactions between QTLs and polygenic backgrounds. However, analyzing a diverse panel constitutes a challenge for statistical analysis. The statistical model must account for possible interactions between a QTL and the panel structure while strictly controlling the detection error rate. Although models to detect population-specific QTLs have already been developed, they rely on prior information about the population structure. In practice, this prior information may be missing as many genome-wide association study (GWAS) panels exhibit complex population structures. The present study introduces 2 new models for detecting QTLs interacting with complex population structures. Both incorporate an interaction term between single nucleotide polymorphism/haplotype block and genetic background into conventional GWAS models. The proposed models were compared with state-of-the-art models through simulation studies that considered QTLs with different levels of interaction with their genetic backgrounds. Results showed that models matching simulation settings were most effective for detecting corresponding QTLs while the proposed models outperformed classical models in detecting QTLs interacting with polygenes. Additionally, when applied to a soybean dataset, one of our models identified putative associated QTLs that conventional models failed to detect. The new models, implemented in the RAINBOWR package available on CRAN, are expected to help uncover complex trait genetic architectures.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651492","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

Divide and conquer approach for genome-wide association studies. 全基因组关联研究的分而治之法。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf019

Mustafa İsmail Özkaraca, Mulya Agung, Pau Navarro, Albert Tenesa

{"title":"Divide and conquer approach for genome-wide association studies.","authors":"Mustafa İsmail Özkaraca, Mulya Agung, Pau Navarro, Albert Tenesa","doi":"10.1093/genetics/iyaf019","DOIUrl":"10.1093/genetics/iyaf019","url":null,"abstract":"Genome-wide association studies (GWAS) are computationally intensive, requiring significant time and resources with computational complexity scaling at least linearly with sample size. Here, we present an accurate and resource-efficient pipeline for GWAS that mitigates the impact of sample size on computational demands. Our approach involves (1) randomly partitioning the cohort into equally sized sub-cohorts, (2) conducting independent GWAS within each sub-cohort, and (3) integrating the results using a novel meta-analysis technique that accounts for population structure and other confounders between sub-cohorts. Importantly, we demonstrate through simulations and real-data examples in humans that our approach effectively manages analyzing related individuals, a critical factor in real datasets, while controlling for inflated effect sizes, a phenomenon known as winner's curse. We show that our method achieves the same discovery levels as standard approaches but with significantly reduced computational costs. Additionally, it is well-suited for incremental GWAS as new samples are added over time. Our implementation within a bioinformatics workflow management system enhances reproducibility and scalability.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626297","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

Substitution load revisited: a high proportion of deaths can be selective. 重新审视替代负荷：高比例的死亡可能是选择性的。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf011

Joseph Matheson, Moises Exposito-Alonso, Joanna Masel

{"title":"Substitution load revisited: a high proportion of deaths can be selective.","authors":"Joseph Matheson, Moises Exposito-Alonso, Joanna Masel","doi":"10.1093/genetics/iyaf011","DOIUrl":"10.1093/genetics/iyaf011","url":null,"abstract":"Haldane's Dilemma refers to the concern that the need for many \"selective deaths\" to complete a substitution (i.e. selective sweep) creates a speed limit to adaptation. However, discussion of this concern has been marked by confusion, especially with respect to the term \"substitution load\". Here, we distinguish different historical lines of reasoning, and identify one, focused on finite reproductive excess and the proportion of deaths that are \"selective\" (i.e. causally contribute to adaptive allele frequency changes), that has not yet been fully addressed. We develop this into a more general theoretical model that can apply to populations with any life history, even those for which a generation or even an individual are not well defined. The actual speed of adaptive evolution is coupled to the proportion of deaths that are selective. The degree to which reproductive excess enables a high proportion of selective deaths depends on the details of when selection takes place relative to density regulation, and there is therefore no general expression for a speed limit. To make these concepts concrete, we estimate both reproductive excess, and the proportion of deaths that are selective, from a dataset measuring survival of 517 different genotypes of Arabidopsis thaliana grown in 8 different environmental conditions. In this dataset, a much higher proportion of deaths contribute to adaptation, in all environmental conditions, than the 10% cap that was anticipated as substantially restricting adaptation during historical discussions of speed limits.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042733","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

Evaluating ARG-estimation methods in the context of estimating population-mean polygenic score histories. 在估计人口平均多基因评分史的背景下评估arg估计方法。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf033

Dandan Peng, Obadiah J Mulder, Michael D Edge

{"title":"Evaluating ARG-estimation methods in the context of estimating population-mean polygenic score histories.","authors":"Dandan Peng, Obadiah J Mulder, Michael D Edge","doi":"10.1093/genetics/iyaf033","DOIUrl":"10.1093/genetics/iyaf033","url":null,"abstract":"Scalable methods for estimating marginal coalescent trees across the genome present new opportunities for studying evolution and have generated considerable excitement, with new methods extending scalability to thousands of samples. Benchmarking of the available methods has revealed general tradeoffs between accuracy and scalability, but performance in downstream applications has not always been easily predictable from general performance measures, suggesting that specific features of the ancestral recombination graph (ARG) may be important for specific downstream applications of estimated ARGs. To exemplify this point, we benchmark ARG estimation methods with respect to a specific set of methods for estimating the historical time course of a population-mean polygenic score (PGS) using the marginal coalescent trees encoded by the ARG. Here, we examine the performance in simulation of seven ARG estimation methods: ARGweaver, RENT+, Relate, tsinfer+tsdate, ARG-Needle, ASMC-clust, and SINGER, using their estimated coalescent trees and examining bias, mean squared error, confidence interval coverage, and Type I and II error rates of the downstream methods. Although it does not scale to the sample sizes attainable by other new methods, SINGER produced the most accurate estimated PGS histories in many instances, even when Relate, tsinfer+tsdate, ARG-Needle, and ASMC-clust used samples 10 or more times as large as those used by SINGER. In general, the best choice of method depends on the number of samples available and the historical time period of interest. In particular, the unprecedented sample sizes allowed by Relate, tsinfer+tsdate, ARG-Needle, and ASMC-clust are of greatest importance when the recent past is of interest-further back in time, most of the tree has coalesced, and differences in contemporary sample size are less salient.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574437","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

Season-specific dominance broadly stabilizes polymorphism under symmetric and asymmetric multivoltinism. 在对称和非对称多重遗传下，季节特异性显性广泛稳定多态性。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf028

Evgeny Brud

{"title":"Season-specific dominance broadly stabilizes polymorphism under symmetric and asymmetric multivoltinism.","authors":"Evgeny Brud","doi":"10.1093/genetics/iyaf028","DOIUrl":"10.1093/genetics/iyaf028","url":null,"abstract":"Seasonality causes intraannual fitness changes in multivoltine populations (defined as having multiple generations per year). While it is well-known that seasonally balanced polymorphism can be established by overdominance in geometric mean fitness, an unsettled aspect of the deterministic theory is the relative contribution of various season-specific dominance mechanisms to the potential for polymorphism. In particular, the relative importance of seasonal reversals in allelic dominance, where the alleles at a locus alternate in recessivity of their deleterious effects, merits clarification. Here, I analyze the parameter space for the discrete generation two-season multivoltine model and find that biallelic polymorphism is easily maintained owing to an abundance of stabilizing dominance schemes, and moreover, a substantial fraction of these schemes are nonreversing with the season (∼25-50%). In addition, I derive the approximate equilibrium allele frequency cycle under bivoltinism and find that the amplitude of allelic oscillation is maximized by nonreversing dominance if the homozygous fitnesses (per annum) are roughly symmetric. Lastly, I derive conditions for the intralocus evolution of dominance. These predict a long-term trend toward maximally beneficial reversal. Overall, the results counter the disproportionate emphasis placed on dominance reversal as a stabilizing mechanism and clarify that nonreversing dominance is expected to frequently characterize seasonally fluctuating alleles under both weak and strong selection, especially in their early history.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558462","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

Activated SKN-1 alters the aging trajectories of long-lived Caenorhabditis elegans mutants. 活化的SKN-1改变了长寿的秀丽隐杆线虫突变体的衰老轨迹。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf016

Chris D Turner, Sean P Curran

{"title":"Activated SKN-1 alters the aging trajectories of long-lived Caenorhabditis elegans mutants.","authors":"Chris D Turner, Sean P Curran","doi":"10.1093/genetics/iyaf016","DOIUrl":"10.1093/genetics/iyaf016","url":null,"abstract":"In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here, we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation. A hallmark of animals with constitutive SKN-1 activation is the age-dependent loss of somatic lipids, and this phenotype is linked to a general reduction in survival in animals harboring the skn-1gf allele. Surprisingly, daf-2lf; skn-1gf double mutant animals do not redistribute somatic lipids, which suggests the insulin signaling pathway functions downstream of SKN-1 in the maintenance of lipid distribution. As expected, the eat-2lf allele, which independently activates SKN-1, continues to display somatic lipid depletion in older ages with and without the skn-1gf activating mutation. In contrast, the presence of the skn-1gf allele does not lead to somatic lipid redistribution in glp-1lf animals that lack a proliferating germline. Taken together, these studies support a genetic model where SKN-1 activity is an important regulator of lipid mobilization in response to nutrient availability that fuels the developing germline by engaging the daf-2/insulin receptor pathway.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060914","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

Conserved components of the macroautophagy machinery in Caenorhabditis elegans. 秀丽隐杆线虫巨噬机制的保守成分。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf007

Hong Zhang, Alicia Meléndez

引用次数: 0

Biobanks in GENETICS and G3: tackling the statistical challenges. 遗传学和G3中的生物库：应对统计挑战。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf046

Lauren M McIntyre

引用次数: 0

Tudor domain containing protein 5-like identifies a novel germline body and regulates maternal RNAs during oogenesis in Drosophila. Tudor domain containing protein 5-like （Tdrd5l）在果蝇卵发生过程中识别一种新的种系体并调控母体rna。

IF 3.3 3区生物学

Genetics Pub Date : 2025-04-17 DOI: 10.1093/genetics/iyaf024

Caitlin Pozmanter, Leif Benner, Sydney E Kelly, Harrison Curnutte, Laura Emilfork, Mark Van Doren

{"title":"Tudor domain containing protein 5-like identifies a novel germline body and regulates maternal RNAs during oogenesis in Drosophila.","authors":"Caitlin Pozmanter, Leif Benner, Sydney E Kelly, Harrison Curnutte, Laura Emilfork, Mark Van Doren","doi":"10.1093/genetics/iyaf024","DOIUrl":"10.1093/genetics/iyaf024","url":null,"abstract":"Tudor domain-containing proteins are conserved across the animal kingdom for their function in germline development and fertility. Previously, we demonstrated that Tudor domain-containing protein 5-like plays an important role in the germline where it promotes male identity. However, Tudor domain-containing protein 5-like is also expressed in both the ovary and testis during later stages of germline development, suggesting that it plays a role in germline differentiation in both sexes. We found that Tudor domain-containing protein 5-like localizes to a potentially novel germline body and plays a role in posttranscriptional gene regulation. Additionally, embryos laid by Tdrd5l-mutant females exhibited reduced viability and displayed dorsal appendage defects suggesting a failure of proper dorsal-ventral patterning. As dorsal-ventral patterning is dependent on gurken (grk), we examined Gurken expression during oogenesis. We observed premature accumulation of Gurken protein in nurse cells indicating that translation is no longer properly repressed during mRNA transport to the oocyte. We also observed increased nurse cell accumulation of the cytoplasmic polyadenylation element binding protein Oo18 RNA-binding protein, a translational activator of grk. Decreasing orb function was able to partially rescue the Tdrd5l-mutant phenotype, and so defects in Orb expression are likely a primary cause of the defects in Tdrd5l mutants. Our data indicate that Tdrd5l is important for translational repression of maternal mRNAs such as orb, and possibly others, following their synthesis in the nurse cells and during their transport to the oocyte.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469741","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