IF 5.1 3区生物学

Genetics Pub Date : 2026-05-07 DOI: 10.1093/genetics/iyag115

Raunak Dutta, Lihong Wan, David Murtha, Tyler Nagosky, Nancy M Hollingsworth

引用次数: 0

Strong amplification of quantitative genetic variation under a balance between mutation and fluctuating stabilizing selection. 在突变和波动稳定选择的平衡下，数量遗传变异的强烈扩增。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag063

Jason Bertram, Zahra Shafiei

{"title":"Strong amplification of quantitative genetic variation under a balance between mutation and fluctuating stabilizing selection.","authors":"Jason Bertram, Zahra Shafiei","doi":"10.1093/genetics/iyag063","DOIUrl":"10.1093/genetics/iyag063","url":null,"abstract":"The observation of high heritability in most quantitative traits has been a long-standing puzzle. There is a general consensus that simple models of quantitative genetic variation, which are mostly founded on the assumption of mutation-selection balance in a constant environment, have failed to explain high heritability. To make matters worse, the reasons for failure are unknown, leaving little to guide future model developments. Here we revisit this puzzle by taking the canonical Latter-Bulmer (LB) model and relaxing the assumption of perfect environmental stasis. Instead we assume that the trait optimum changes slowly but steadily in a stochastic manner, similar to models used for phylogenetic comparative methods. We show that our model behaves qualitatively differently to its stationary optimum counterpart even though the optimum only changes slowly. This is the result of a feedback between the adaptation rate and selection coefficient fluctuations. The heritability predictions resulting from this feedback are more consistent with observations and also less sensitive to evolutionary parameters than the classical LB model. We derive a simple formula to predict genetic variation in our model which helps to explain some of our counter-intuitive results and which should be useful for understanding the potential influence of fluctuations in future work. Since the feedback driving our results should also occur in more complex models e.g. with multiple traits, we argue that environmental change has been an essential biological ingredient missing in most previous mutation-selection balance models of quantitative trait heritability.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370218","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

Genetic and environmental determinants of multicellular-like phenotypes in fission yeast. 裂变酵母多细胞样表型的遗传和环境决定因素。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag064

Bence Kӧvér, Céleste E Cohen, Ladislav Seres, Saniya Raut, Markus Ralser, Benjamin M Heineike, Jürg Bähler

{"title":"Genetic and environmental determinants of multicellular-like phenotypes in fission yeast.","authors":"Bence Kӧvér, Céleste E Cohen, Ladislav Seres, Saniya Raut, Markus Ralser, Benjamin M Heineike, Jürg Bähler","doi":"10.1093/genetics/iyag064","DOIUrl":"10.1093/genetics/iyag064","url":null,"abstract":"Multicellular fungi have repeatedly given rise to primarily unicellular yeast species. Some of these, including the fission yeast Schizosaccharomyces pombe, can revert to multicellular-like phenotypes (MLPs). As MLP formation remains understudied in fission yeast compared with budding yeast, we aimed to narrow this gap. We developed high-throughput assays for two MLPs: flocculation and surface adhesion, which correlated in minimal media, suggesting a common mechanism. Using a library of 57 natural S. pombe isolates, we found that MLP formation varied widely across different nutrient and drug conditions. In a segregant S. pombe library generated by crossing an adhesive natural isolate with the standard laboratory strain, MLP formation correlated with expression levels of the transcription factor gene mbx2 and several flocculin genes. Quantitative trait locus (QTL) mapping of MLP formation located a frameshift mutation in the srb11 gene encoding cyclin C, a part of the Cdk8 kinase module (CKM) of the Mediator complex. Deletion of either srb11 or srb10 (encoding the Cdk8 kinase) resulted in MLP formation through upregulation of mbx2. Screening a library of 3,721 gene-deletion strains uncovered 31 additional genes involved in surface adhesion, including 15 genes not previously associated with MLPs in fission or budding yeast. Notably, deletion of srb11, unlike deletions of the 31 hits, did not compromise cell growth, which might explain its natural occurrence as a QTL for MLP formation. Our findings provide a comprehensive genetic survey of MLP formation in fission yeast and a functional description of a causal variant that drives MLP formation in nature.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370232","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

Mutational landscape and molecular bases of echinocandin resistance in Saccharomyces cerevisiae. 酿酒酵母菌棘白菌素抗性的突变景观和分子基础。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag055

Romain Durand, Alexandre G Torbey, Mathieu Giguere, Alicia Pageau, Alexandre K Dubé, Patrick Lagüe, Christian R Landry

{"title":"Mutational landscape and molecular bases of echinocandin resistance in Saccharomyces cerevisiae.","authors":"Romain Durand, Alexandre G Torbey, Mathieu Giguere, Alicia Pageau, Alexandre K Dubé, Patrick Lagüe, Christian R Landry","doi":"10.1093/genetics/iyag055","DOIUrl":"10.1093/genetics/iyag055","url":null,"abstract":"One of the front-line drug classes used to treat invasive fungal infections is echinocandins, which target the fungal-specific beta-glucan synthase (Fks). Treatment failure due to resistance often coincides with mutations in 3 protein regions defined as hotspots. Unfortunately, the scarcity of the mutational data reported, combined with the large size and membrane-embedded nature of the enzyme hinder any effort to characterize genotype-phenotype links. Recent advances in solving the structure of Fks bring us one step closer to reliable predictions of the binding modes of each echinocandin. To help with that endeavor, we used molecular dynamics simulations to develop a membrane-embedded model of Fks that captures key structural and environmental features. Our results show that the 3 hotspots shape a single solvent-exposed binding cavity, hinting at the orientation and positioning of echinocandins. This structural framework is integrated with deep-mutational scanning to comprehensively assess the impact of mutations across the 3 hotspots in the model yeast Saccharomyces cerevisiae. We elucidate several key molecular bases of resistance to the 3 most widely used echinocandins; anidulafungin, caspofungin and micafungin and provide clues to better understand intrinsic resistance of critical fungal pathogens.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328056","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

Publisher's Note on 39 papers regarding Digital Object Identifiers. 出版商对39篇关于数字对象标识符的论文的注释。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag052

引用次数: 0

The claudin-like molecule CLC-3 regulates cholinergic neurotransmission in Caenorhabditis elegans. CLC-3类分子调控秀丽隐杆线虫胆碱能神经传递。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag070

Aishwarya Ahuja, Anusha Rastogi, Haowen Liu, Akankshya Sahu, Harinika Kumar, Jagannath Jayaraj, Zhitao Hu, Kavita Babu

{"title":"The claudin-like molecule CLC-3 regulates cholinergic neurotransmission in Caenorhabditis elegans.","authors":"Aishwarya Ahuja, Anusha Rastogi, Haowen Liu, Akankshya Sahu, Harinika Kumar, Jagannath Jayaraj, Zhitao Hu, Kavita Babu","doi":"10.1093/genetics/iyag070","DOIUrl":"10.1093/genetics/iyag070","url":null,"abstract":"Cell adhesion molecules (CAMs) play important roles in neurons, contributing to nervous system development, synapse formation, and plasticity. A subset of CAMs, Claudins, known for their roles at tight junctions, remains underexplored in neurons. Recent studies in Caenorhabditis elegans have begun to reveal neuronal functions of claudin-like proteins. However, a systematic analysis of their neuronal expression has not been performed. We conducted a transcriptional reporter screen for claudin-like genes in C. elegans and identified several candidates showing neuronal expression, highlighting possible roles for claudins in the nervous system. One candidate, clc-3, showed robust expression in head, tail, and ventral cord neurons, with no detectable expression in non-neuronal tissues. Functional analyses of clc-3 mutants revealed increased body-bend amplitudes and elevated evoked postsynaptic currents at the cholinergic neuromuscular synapses. Imaging and molecular interaction studies demonstrated that CLC-3 likely interacts with the actin-binding protein NAB-1 to regulate cholinergic transmission. Our findings identify CLC-3 as a neuronally expressed claudin that regulates motor system output, likely through synaptic vesicle organization and illustrates how changes in synaptic function affect animal behavior.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500535","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

Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans. 最小选择条件下秀丽隐杆线虫突变率、分子谱和适应度效应的进化。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag085

Sayran Saber, Md Monjurul Islam Rifat, Fahimeh Rahimi, Michael Snyder, Amber Singh, Benjamin Eickwort, Yell Newhall, Moein Rajaei, Ayush Shekhar Saxena, Robyn E Tanny, Vaishali Katju, Erik C Andersen, Juannan Zhou, Charles F Baer

{"title":"Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans.","authors":"Sayran Saber, Md Monjurul Islam Rifat, Fahimeh Rahimi, Michael Snyder, Amber Singh, Benjamin Eickwort, Yell Newhall, Moein Rajaei, Ayush Shekhar Saxena, Robyn E Tanny, Vaishali Katju, Erik C Andersen, Juannan Zhou, Charles F Baer","doi":"10.1093/genetics/iyag085","DOIUrl":"10.1093/genetics/iyag085","url":null,"abstract":"The rate, molecular spectrum, and fitness effects of mutations vary at all levels of the biological hierarchy, from within individual genomes to among taxonomic domains. Understanding the evolutionary factors underpinning that variation is of fundamental importance to biology. Accurate quantification of the properties of mutations requires that other evolutionary forces, especially natural selection, be minimized as much as possible. To investigate the evolution of the mutational process in Caenorhabditis elegans, we propagated a set of 100 \"first order\" mutation accumulation (O1MA) lines under minimal selection for ∼150 generations, divided each O1MA line into 2 \"second order\" MA (O2MA) lines and propagated them for another ∼150 generations, at which time the genome of each O2MA line was sequenced, and a subset of 50 O1MA families was assayed for competitive fitness. Over the course of the experiment, the mean nucleotide substitution mutation rate did not change, but the variance increased. In contrast, the indel mutation rate increased significantly. The 2 types of mutations fulfill the predictions of different theoretical models for the evolution of mutation rate. These results reinforce previous findings that the rate of indels is more sensitive to endogenous stress than the rate of nucleotide substitutions. Several evolutionary quandaries could be resolved if deleterious mutations interact synergistically (negative epistasis). Evidence for synergistic epistasis is famously inconclusive, although there is reason to think it may be more detectable under competitive conditions. However, a model of constant mutational effects on competitive fitness explains the results significantly better than a model including epistasis.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515981","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

Kar4 acts as a Ste12 regulator in Saccharomyces cerevisiae, promoting Ste12 binding to a specific DNA motif genome-wide. Kar4在酿酒酵母中作为Ste12调节因子，促进Ste12与全基因组特定DNA基元的结合。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag051

Jason V Rogers, Amanda Yeo, Val Meleshkevich, Hernan Lorenzi, Mark D Rose, Orna Cohen-Fix

{"title":"Kar4 acts as a Ste12 regulator in Saccharomyces cerevisiae, promoting Ste12 binding to a specific DNA motif genome-wide.","authors":"Jason V Rogers, Amanda Yeo, Val Meleshkevich, Hernan Lorenzi, Mark D Rose, Orna Cohen-Fix","doi":"10.1093/genetics/iyag051","DOIUrl":"10.1093/genetics/iyag051","url":null,"abstract":"Transcription factors must often transcribe different genes under different conditions. To achieve this, DNA-binding specificity is often constrained by binding to cofactors or other transcription factors. Kar4 is a putative transcription factor required for efficient mating in the budding yeast Saccharomyces cerevisiae. Kar4 functions with Ste12, the master transcriptional regulator of the yeast mating pheromone response, to promote the transcription of a subset of Ste12 target genes. However, the mechanism by which Kar4 modulates Ste12 activity has remained uncertain. Here, we examined Kar4's function at the levels of transcription (RNA-seq) and Ste12 DNA binding (ChIP-exo). We show that Kar4 promotes Ste12 binding to nearly all Ste12 DNA-binding sites associated with transcriptionally upregulated genes, even if their upregulation is not dependent on Kar4. We further found that the majority of Ste12-binding sites have 2 pheromone response elements (PREs) separated by 4 nucleotides in a head-to-tail orientation (H-T 4 motif). Sites associated with Kar4-dependent transcription have PREs with more mismatches, and substantially lower Ste12 occupancy in kar4Δ cells, than sites linked to Kar4-independent transcription. During the pheromone response in kar4Δ cells, Ste12 exhibits increased binding to non-H-T 4 motifs, particularly T-T 3 motifs, resulting in the abnormal upregulation of many genes not transcribed in wild-type. We propose that Kar4 functions by increasing the DNA-binding specificity of Ste12 globally, promoting its binding primarily to H-T 4 motifs. Lastly, we uncovered several novel aspects of the pheromone response, including a broad role for the Crz1 transcription factor, pheromone-responsive intergenic transcripts, and pheromone-induced stress responses.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277448","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

Germline and male somatic determinants of sperm length divergence in Drosophila: implications for postcopulatory sexual selection. 果蝇精子长度差异的生殖系和雄性体细胞决定因素：交配后性选择的意义。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag069

Kaori Nishimura, Miho Asaoka, Toshiyuki Takano-Shimizu-Kouno

{"title":"Germline and male somatic determinants of sperm length divergence in Drosophila: implications for postcopulatory sexual selection.","authors":"Kaori Nishimura, Miho Asaoka, Toshiyuki Takano-Shimizu-Kouno","doi":"10.1093/genetics/iyag069","DOIUrl":"10.1093/genetics/iyag069","url":null,"abstract":"Sperm display remarkable diversity in size and morphology, especially in insects. Sperm length varies by several hundred-fold within Drosophila alone. In the model species Drosophila melanogaster, sperm are approximately 1.7 times longer than those of its close relatives Drosophila simulans and Drosophila mauritiana. However, the developmental mechanisms underlying such rapid divergence in sperm traits remain poorly understood. Somatic hub and cyst cells are essential for the maintenance of germline stem cells in Drosophila spermatogenesis, yet their contribution to cell growth later in spermatogenesis remains unclear. Here, we used primordial germ cell (PGC) xenotransplantation to determine whether sperm length regulation is cell autonomous or influenced by the somatic environment of the testes. When D. simulans PGCs were transplanted into agametic D. melanogaster embryos, the resulting sperm were indistinguishable in length from those of D. simulans donor males and remained significantly shorter than the sperm of D. melanogaster males. Our results suggest that the dramatic diversification in sperm length shaped by postcopulatory sexual selection in the Drosophila lineage has been largely driven by cell-autonomous modifications in the germ line.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436834","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

Crosstalk between and developmental dynamics of Caenorhabditis elegans Argonaute proteins. 秀丽隐杆线虫Argonaute蛋白间的串扰及发育动力学。

IF 5.1 3区生物学

Genetics Pub Date : 2026-05-06 DOI: 10.1093/genetics/iyag077

Ann-Sophie Seistrup, Emily Nischwitz, Falk Butter, René F Ketting

{"title":"Crosstalk between and developmental dynamics of Caenorhabditis elegans Argonaute proteins.","authors":"Ann-Sophie Seistrup, Emily Nischwitz, Falk Butter, René F Ketting","doi":"10.1093/genetics/iyag077","DOIUrl":"10.1093/genetics/iyag077","url":null,"abstract":"Gene regulation via Argonaute-bound small RNAs is a broadly conserved mechanism present in all domains of life. The nematode Caenorhabditis elegans expresses several worm-specific Argonautes (WAGOs), which interact with the small RNAs known as 22G-RNAs. These WAGOs have roles in gene regulation, transposon-defense as well as in viral control and experimentally induced RNA interference. Despite many studies, direct relationships between WAGO targeting, as defined by 22G-RNA sequences, and mRNA abundance are not clear. Also, the effects of developmental stage and WAGO interconnectivity have been under-studied thus far. We studied these aspects for 2 germline-expressed WAGO proteins, WAGO-1 and WAGO-3. We show that WAGO-1 mostly affects 22G-RNA expression in gravid adult worms, while WAGO-3 predominantly affects 22G-RNA expression in embryos. Furthermore, we detect a link between WAGO-3 and the maternal 26G-RNA pathway governed by the Argonaute protein ERGO-1, and between WAGO-1 and the paternal 26G-RNA pathway governed by the Argonautes ALG-3/4. We also demonstrate that, globally speaking, loss of WAGO-1 or WAGO-3 does not result in upregulation of their target mRNAs, as defined by 22G-RNA complementarity. Finally, metagene analysis of 22G-RNA profiles suggests loss of 1 WAGO protein leads to shifts in WAGO 22G-RNA binding. Overall, we conclude that WAGO-1 and WAGO-3 are developmentally dynamic, are embedded in distinct regulatory networks, and potential silencing of individual mRNAs by these WAGO proteins is hard to assess by simple loss-of-function studies.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500370","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

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