Genetics最新文献_第4页

Correction to: How the concentric organization of the nucleolus and chromatin ensures accuracy of ribosome biogenesis and drives transport. 更正：核仁和染色质的同心组织如何确保核糖体生物发生的准确性并驱动运输。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-26 DOI: 10.1093/genetics/iyaf093

引用次数: 0

Gut length evolved under sexual conflict in Lake Malawi cichlids. 马拉维湖慈鲷的肠长在性冲突中进化。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-26 DOI: 10.1093/genetics/iyaf102

Aldo Carmona Baez, Patrick J Ciccotto, Emily C Moore, Erin N Peterson, Melissa S Lamm, Natalie B Roberts, Kaitlin P Coyle, M Kaitlyn Barker, Ethan Dickson, Amanda N Cass, Guilherme S Pereira, Zhao-Bang Zeng, Rafael F Guerrero, Reade B Roberts

{"title":"Gut length evolved under sexual conflict in Lake Malawi cichlids.","authors":"Aldo Carmona Baez, Patrick J Ciccotto, Emily C Moore, Erin N Peterson, Melissa S Lamm, Natalie B Roberts, Kaitlin P Coyle, M Kaitlyn Barker, Ethan Dickson, Amanda N Cass, Guilherme S Pereira, Zhao-Bang Zeng, Rafael F Guerrero, Reade B Roberts","doi":"10.1093/genetics/iyaf102","DOIUrl":"https://doi.org/10.1093/genetics/iyaf102","url":null,"abstract":"Variation in gastrointestinal morphology is associated with dietary specialization across the animal kingdom. Gut length generally correlates with trophic level, and increased gut length in herbivores is a classic example of adaptation to cope with diets having a lower nutrient content and a higher proportion of refractory material. However, the genetic basis of gut length variation remains largely unstudied, partly due to the inaccessibility and plasticity of the gut tissue, as well as the lack of dietary diversity within traditional model organisms relative to that observed among species belonging to different trophic levels. Here, we confirm the genetic basis of gut length variation among recently evolved Lake Malawi cichlid fish species with different dietary adaptations. We then produce interspecific, inter-trophic-level hybrids to map evolved differences in intestinal length in an F2 mapping cross between Metriaclima mbenjii, an omnivore with a relatively long gut, and Aulonocara koningsi, a carnivore with a relatively short gut. We identify numerous candidate quantitative trait loci for evolved differences in intestinal length. These quantitative trait loci are predominantly sex-specific, supporting an evolutionary history of sexual conflicts for the gut. We also identify epistatic interactions potentially associated with canalization and the maintenance of cryptic variation in the cichlid adaptive radiation. Overall, our results suggest a complex, polygenic evolution of gut length variation associated with trophic level differences among cichlids, as well as conflicts and interactions that may be involved in evolutionary processes underlying other traits in cichlids.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152569","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

Evolutionary rescue by aneuploidy in tumors exposed to anti-cancer drugs. 暴露于抗癌药物的肿瘤非整倍体的进化拯救。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-22 DOI: 10.1093/genetics/iyaf098

Remus Stana, Uri Ben-David, Daniel B Weissman, Yoav Ram

{"title":"Evolutionary rescue by aneuploidy in tumors exposed to anti-cancer drugs.","authors":"Remus Stana, Uri Ben-David, Daniel B Weissman, Yoav Ram","doi":"10.1093/genetics/iyaf098","DOIUrl":"https://doi.org/10.1093/genetics/iyaf098","url":null,"abstract":"Evolutionary rescue occurs when a population, facing a sudden environmental change that would otherwise lead to extinction, adapts through beneficial mutations, allowing it to recover and persist. A prime example of evolutionary rescue is the ability of cancer to survive exposure to treatment. One evolutionary mechanism by which a population of cancer cells can adapt to chemotherapy is aneuploidy. Aneuploid cancer cells can be more fit in an environment altered by anti-cancer drugs, in part because aneuploidy may disrupt the pathways targeted by the drugs. Indeed, aneuploidy is highly prevalent in tumors, and some anti-cancer drugs fight cancer by increasing chromosomal instability. Here, we model the impact of aneuploidy on the fate of a population of cancer cells. We use multi-type branching processes to approximate the probability that a tumor survives drug treatment as a function of the initial tumor size, the rates at which aneuploidy and other beneficial mutations occur, and the growth rates of the drug-sensitive and drug-resistant cells. We also investigate the effect of the pre-existent aneuploid cells on the probability of evolutionary rescue. Finally, we estimate the tumor's mean recurrence time to revert to its initial size following treatment and evolutionary rescue. We propose that aneuploidy can play an essential role in the relapse of smaller secondary tumors.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129033","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

Interpreting SNP heritability in admixed populations. 在混合人群中解释SNP遗传力。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-22 DOI: 10.1093/genetics/iyaf100

Jinguo Huang, Nicole Kleman, Saonli Basu, Mark D Shriver, Arslan A Zaidi

{"title":"Interpreting SNP heritability in admixed populations.","authors":"Jinguo Huang, Nicole Kleman, Saonli Basu, Mark D Shriver, Arslan A Zaidi","doi":"10.1093/genetics/iyaf100","DOIUrl":"10.1093/genetics/iyaf100","url":null,"abstract":"SNP heritability (h2snp) is defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability (h), being equal to it if all causal variants are genotyped. Despite the simple intuition behind h2snp, its interpretation and equivalence to h2 is unclear, particularly in the presence of admixture and assortative mating. Here we use analytical theory and simulations to describe the behavior of h2 and three widely used random-effect estimators of h2snp -- Genome-wide restricted maximum likelihood, Haseman-Elston regression, and LD score regression -- in admixed populations. We show that h2snp estimates can be biased in admixed populations, even if all causal variants are genotyped and in the absence of confounding due to shared environment. This is largely because admixture generates directional LD, which contributes to the genetic variance, and therefore to heritability. Random-effect estimators of h2snp, because they assume that SNP effects are independent, do not capture the contribution, which can be positive or negative depending on the genetic architecture, leading to under- or over-estimates of h2snp relative to h2. For the same reason, estimates of local ancestry heritability (ĥ2γ) are also biased in the presence of directional LD. We describe this bias in ĥ2snp and ĥ2γ as a function of admixture history and the genetic architecture of the trait, clarifying their interpretation and implication for genome-wide association studies and polygenic prediction in admixed populations.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129040","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

MutSgamma promotes meiotic recombination and homolog pairing in mouse spermatocytes. MutSgamma促进小鼠精母细胞减数分裂重组和同源配对。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-22 DOI: 10.1093/genetics/iyaf099

Melissa Frasca, Lakshmi Paniker, Rhea Kang, Parijat Chakraborty, Aastha Pandey, Jessica LoPresti, Francesca Cole

{"title":"MutSgamma promotes meiotic recombination and homolog pairing in mouse spermatocytes.","authors":"Melissa Frasca, Lakshmi Paniker, Rhea Kang, Parijat Chakraborty, Aastha Pandey, Jessica LoPresti, Francesca Cole","doi":"10.1093/genetics/iyaf099","DOIUrl":"https://doi.org/10.1093/genetics/iyaf099","url":null,"abstract":"DNA repair by homologous recombination is required for parental chromosomes (homologs) to accurately segregate during mammalian meiosis. Meiotic recombination promotes but also relies upon pairing between homologs. This mutual dependence and the differential reliance between recombination and pairing in well-studied organisms has been difficult to deconstruct in the mammalian context. In budding yeast, MutSgamma, a heterodimer between MSH4 and MSH5 promotes crossover-specific recombination by protecting precursors, and in many organisms plays roles in pairing and synaptonemal complex formation. We use recombination and cytological assays to infer the role of MutSgamma in mouse spermatocytes. We find in two alleles of Msh5 - a null and one bearing a mutation in its ATPase domain, that spermatocytes are severely compromised for recombination producing only a small fraction of noncrossovers. However, they are more proficient in interhomolog pairing particularly on the longer chromosomes than spermatocytes lacking meiotic recombination entirely. We propose MutSgamma plays an earlier role in mouse than in budding yeast to stabilize D-loops upstream of all interhomolog recombination. Further, that nascent recombination interactions can promote successful interhomolog pairing despite not completing recombination.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129059","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

Enabling data-driven discoveries in evolutionary genetics and genomics. 在进化遗传学和基因组学中实现数据驱动的发现。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-20 DOI: 10.1093/genetics/iyaf084

Sudhir Kumar

引用次数: 0

A rapid accurate approach to inferring pedigrees in endogamous populations. 一种快速准确地推断内婚制种群谱系的方法。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-20 DOI: 10.1093/genetics/iyaf094

Cole M Williams, Brooke A Scelza, Sarah D Slack, Neus Font-Porterias, Dana R Al-Hindi, Rasika A Mathias, Harold Watson, Kathleen C Barnes, Ethan Lange, Randi K Johnson, Christopher R Gignoux, Sohini Ramachandran, Brenna M Henn

{"title":"A rapid accurate approach to inferring pedigrees in endogamous populations.","authors":"Cole M Williams, Brooke A Scelza, Sarah D Slack, Neus Font-Porterias, Dana R Al-Hindi, Rasika A Mathias, Harold Watson, Kathleen C Barnes, Ethan Lange, Randi K Johnson, Christopher R Gignoux, Sohini Ramachandran, Brenna M Henn","doi":"10.1093/genetics/iyaf094","DOIUrl":"https://doi.org/10.1093/genetics/iyaf094","url":null,"abstract":"Accurate reconstruction of pedigrees from genetic data remains a challenging problem. Many relationship categories (e.g. half-sibships versus avuncular) can be difficult to distinguish without external information. Pedigree inference algorithms are often trained on European-descent families in urban locations. Thus, existing methods tend to perform poorly in endogamous populations for which there may be reticulations within the pedigrees and elevated haplotype sharing. We present a simple, rapid algorithm which initially uses only high-confidence first-degree relationships to seed a machine learning step based on summary statistics of identity-by-descent (IBD) sharing. One of these statistics, our ``haplotype score'', is novel and can be used to: (1) distinguish half-sibling pairs from avuncular or grandparent-grandchildren pairs; and (2) assign individuals to ancestor versus descendant generation. We test our approach in a sample of ∼700 individuals from northern Namibia, sampled from an endogamous population called the Himba. Due to a culture of concurrent relationships in the Himba, there is a high proportion of half-sibships. We accurately identify first through fourth-degree relationships and distinguish between various second-degree relationships: half-sibships, avuncular pairs, and grandparent-grandchildren. We further validate our approach in a second African-descent dataset, the Barbados Asthma Genetics Study (BAGS), and a European-descent founder population from Quebec. Accurate reconstruction of relatives facilitates estimation of allele frequencies, tracing allele trajectories, improved phasing, heritability and other population genomic questions.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112497","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

Quantitative Resolution of Cell Fate in the Early Embryogenesis of Caenorhabditis elegans. 秀丽隐杆线虫早期胚胎发生过程中细胞命运的定量分析。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-20 DOI: 10.1093/genetics/iyaf095

Ruiqi Xiong, Yang Su, Mengchao Yao, Zefei Liu, Jie Lu, Yong-Cong Chen, Ping Ao

{"title":"Quantitative Resolution of Cell Fate in the Early Embryogenesis of Caenorhabditis elegans.","authors":"Ruiqi Xiong, Yang Su, Mengchao Yao, Zefei Liu, Jie Lu, Yong-Cong Chen, Ping Ao","doi":"10.1093/genetics/iyaf095","DOIUrl":"https://doi.org/10.1093/genetics/iyaf095","url":null,"abstract":"The nematode Caenorhabditis elegans exhibits an invariant cell lineage during its development, where the gene-molecular network that regulates the development is crucial for the biological process. While there are many molecular cell atlases describing the phenomena and key molecules involved in cell transformation, the underlying mechanisms from a systems biology perspective have received less attention. Based on an endogenous molecular-cellular theory that relates the molecular mechanisms to biological phenotypes, we constructed a model of the core endogenous network to describe the early stages of embryonic development of the C. elegans. Different cell types and intermediate cell states during development from zygotes to founder cells correspond to the steady states of the network as a nonlinear stochastic dynamical system. Connections between steady states form a topological landscape that encompasses known developmental lineage trajectories. By regulating the expression of agents in the network, we quantitatively simulated the effects of the Wnt and Notch signaling pathway on cell fate transitions and predicted the possible trajectories of transdifferentiation of the AB cell across the lineage. The success of the current study may help advance our understanding of the fundamental principles of developmental biology and cell fate determination, offering an effective tool for the quantitative analysis of cellular processes.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111494","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

More than meets the eye: Mutation of the white gene in Drosophila has broad phenotypic and transcriptomic effects. 超过满足眼睛：在果蝇白色基因突变具有广泛的表型和转录组效应。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-17 DOI: 10.1093/genetics/iyaf097

April Rickle, Krittika Sudhakar, Alix Booms, Ellen Stirtz, Adelheid Lempradl

{"title":"More than meets the eye: Mutation of the white gene in Drosophila has broad phenotypic and transcriptomic effects.","authors":"April Rickle, Krittika Sudhakar, Alix Booms, Ellen Stirtz, Adelheid Lempradl","doi":"10.1093/genetics/iyaf097","DOIUrl":"https://doi.org/10.1093/genetics/iyaf097","url":null,"abstract":"The white gene, one of the most widely used genetic markers in Drosophila research, serves as a standard background mutation for transgene insertions and genetic manipulations. While its primary function involves eye pigmentation, mutations in white have been associated with diverse phenotypic effects, including those related to metabolism, behavior, and stress responses. However, many of the published studies do not account for differences in genetic background, raising concerns about the interpretation of experimental results. To address this, we generated fly lines through 10 generations of backcrossing that are highly genetically similar except at the white locus, minimizing background variation. Given the likely metabolic consequences of white gene deletion and its role in neurotransmitter production, we focused on behavioral, metabolic, and fitness-related traits and performed transcriptomic analysis on adult fly heads. Our findings both confirm and refine previous observations, revealing that some reported effects of white mutation are robust while others likely reflect underlying genetic background differences. These results emphasize the necessity of genetic background control in Drosophila research and warrant caution when using white mutants as a baseline for comparative studies.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086710","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

Conflicting kinesin-14s in a single chromosomal drive haplotype. 在单个染色体驱动单倍型中冲突的驱动蛋白-14。

IF 3.3 3区生物学

Genetics Pub Date : 2025-05-14 DOI: 10.1093/genetics/iyaf091

Meghan J Brady, Anjali Gupta, Jonathan I Gent, Kyle W Swentowsky, Robert L Unckless, R Kelly Dawe

{"title":"Conflicting kinesin-14s in a single chromosomal drive haplotype.","authors":"Meghan J Brady, Anjali Gupta, Jonathan I Gent, Kyle W Swentowsky, Robert L Unckless, R Kelly Dawe","doi":"10.1093/genetics/iyaf091","DOIUrl":"10.1093/genetics/iyaf091","url":null,"abstract":"In maize, there are two meiotic drive systems that target large heterochromatic knobs composed of tandem repeats known as knob180 and TR-1. The first meiotic drive haplotype, Abnormal chromosome 10 (Ab10) confers strong meiotic drive (∼75% transmission as a heterozygote) and encodes two kinesins: KINDR, which associates with knob180 repeats and TRKIN, which associates with TR-1 repeats. Prior data show that meiotic drive is conferred primarily by the KINDR/knob180 system while the TRKIN/TR-1 system seems to have little or no role, making it unclear why Trkin has been maintained in Ab10 haplotypes. The second meiotic drive haplotype, K10L2, confers a low level of meiotic drive (∼51-52%) and only encodes the TRKIN/TR-1 system. Here we used long-read sequencing to assemble the K10L2 haplotype and showed that it has strong homology to an internal portion of the Ab10 haplotype. We also carried out CRISPR mutagenesis to test the role of Trkin on Ab10 and K10L2. The data indicate that the Trkin gene on Ab10 does not improve drive or fitness but instead has a weak deleterious effect when paired with a normal chromosome 10. The deleterious effect is more severe when Ab10 is paired with K10L2: in this context functional Trkin on either chromosome nearly abolishes Ab10 drive. Mathematical modeling based on the empirical data suggest that Trkin is unlikely to persist on Ab10. We conclude that Trkin either confers an advantage to Ab10 in untested circumstances or that it is in the process of being purged from the Ab10 population.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035449","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