Genetics最新文献

{"title":"Revisiting the role of the spindle assembly checkpoint in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae.","authors":"Yue Yao, Ziqing Yin, Fernando R Rosas Bringas, Jonathan Boudeman, Daniele Novarina, Michael Chang","doi":"10.1093/genetics/iyae150","DOIUrl":"10.1093/genetics/iyae150","url":null,"abstract":"<p><p>Multiple pathways are known to suppress the formation of gross chromosomal rearrangements (GCRs), which can cause human diseases including cancer. In contrast, much less is known about pathways that promote their formation. The spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during mitosis, has been reported to promote GCR, possibly by delaying mitosis to allow GCR-inducing DNA repair to occur. Here, we show that this conclusion is the result of an experimental artifact arising from the synthetic lethality caused by the disruption of the SAC and loss of the CIN8 gene, which is often lost in the genetic assay used to select for GCRs. After correcting for this artifact, we find no role of the SAC in promoting GCR.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299278","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}

{"title":"Genetic background affects the strength of crossover interference in house mice.","authors":"Andrew P Morgan, Bret A Payseur","doi":"10.1093/genetics/iyae146","DOIUrl":"10.1093/genetics/iyae146","url":null,"abstract":"<p><p>Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles from M. m. musculus tend to increase recombination rate, while inheriting a M. m. musculus X chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143446","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}

{"title":"Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior.","authors":"Jan Watteyne, Aleksandra Chudinova, Lidia Ripoll-Sánchez, William R Schafer, Isabel Beets","doi":"10.1093/genetics/iyae141","DOIUrl":"10.1093/genetics/iyae141","url":null,"abstract":"<p><p>Neuropeptides are abundant signaling molecules that control neuronal activity and behavior in all animals. Owing in part to its well-defined and compact nervous system, Caenorhabditis elegans has been one of the primary model organisms used to investigate how neuropeptide signaling networks are organized and how these neurochemicals regulate behavior. We here review recent work that has expanded our understanding of the neuropeptidergic signaling network in C. elegans by mapping the evolutionary conservation, the molecular expression, the receptor-ligand interactions, and the system-wide organization of neuropeptide pathways in the C. elegans nervous system. We also describe general insights into neuropeptidergic circuit motifs and the spatiotemporal range of peptidergic transmission that have emerged from in vivo studies on neuropeptide signaling. With efforts ongoing to chart peptide signaling networks in other organisms, the C. elegans neuropeptidergic connectome can serve as a prototype to further understand the organization and the signaling dynamics of these networks at organismal level.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330529","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}

{"title":"Sharp decline in male fertility in F2 hybrids of the female-heterogametic silk moth Bombyx.","authors":"Kana Matsukawa, Yasuko Kato, Aya Yoshida, Hisaka Onishi, Sachiko Nakano, Masanobu Itoh, Toshiyuki Takano-Shimizu-Kouno","doi":"10.1093/genetics/iyae149","DOIUrl":"10.1093/genetics/iyae149","url":null,"abstract":"<p><p>Sexual selection drives rapid evolution of morphological, physiological, and behavioral traits, especially in males, and it may also drive the rapid evolution of hybrid male sterility. Indeed, the faster male theory of speciation was once viewed as a major cause of Haldane's rule in male-heterogametic XY taxa, but is increasingly being replaced by the genetic conflict hypothesis partly because it cannot explain the faster evolution of hybrid female sterility in female-heterogametic ZW taxa. The theory nonetheless predicts that there should be more genes for hybrid male sterility than for hybrid female sterility even in such taxa, but this remains untested. Thus, finding evidence for the faster male theory of reproductive isolation beyond the F1 generation in ZW systems still represents a challenge to studying the impact of sexual selection. In this study, we examined F2 hybrids between the domesticated silkworm Bombyx mori and the wild silk moth Bombyx mandarina, which have ZW sex determination. We found that although only females showed reduced fertility in the F1 generation, the F2 hybrid males had a significant reduction in fertility compared with the parental and F1 males. Importantly, 27% of the F2 males and 15% of the F2 females were completely sterile, suggesting the presence of recessive incompatibilities causing male sterility in female-heterogametic taxa.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394483","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}

{"title":"Life history in Caenorhabditis elegans: from molecular genetics to evolutionary ecology.","authors":"Christian Braendle, Annalise Paaby","doi":"10.1093/genetics/iyae151","DOIUrl":"10.1093/genetics/iyae151","url":null,"abstract":"<p><p>Life history is defined by traits that reflect key components of fitness, especially those relating to reproduction and survival. Research in life history seeks to unravel the relationships among these traits and understand how life history strategies evolve to maximize fitness. As such, life history research integrates the study of the genetic and developmental mechanisms underlying trait determination with the evolutionary and ecological context of Darwinian fitness. As a leading model organism for molecular and developmental genetics, Caenorhabditis elegans is unmatched in the characterization of life history-related processes, including developmental timing and plasticity, reproductive behaviors, sex determination, stress tolerance, and aging. Building on recent studies of natural populations and ecology, the combination of C. elegans' historical research strengths with new insights into trait variation now positions it as a uniquely valuable model for life history research. In this review, we summarize the contributions of C. elegans and related species to life history and its evolution. We begin by reviewing the key characteristics of C. elegans life history, with an emphasis on its distinctive reproductive strategies and notable life cycle plasticity. Next, we explore intraspecific variation in life history traits and its underlying genetic architecture. Finally, we provide an overview of how C. elegans has guided research on major life history transitions both within the genus Caenorhabditis and across the broader phylum Nematoda. While C. elegans is relatively new to life history research, significant progress has been made by leveraging its distinctive biological traits, establishing it as a highly cross-disciplinary system for life history studies.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478459","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}

{"title":"A review of multimodal deep learning methods for genomic-enabled prediction in plant breeding.","authors":"Osval A Montesinos-López, Moises Chavira-Flores, Kiasmiantini, Leo Crespo-Herrera, Carolina Saint Piere, HuiHui Li, Roberto Fritsche-Neto, Khalid Al-Nowibet, Abelardo Montesinos-López, José Crossa","doi":"10.1093/genetics/iyae161","DOIUrl":"https://doi.org/10.1093/genetics/iyae161","url":null,"abstract":"<p><p>Deep learning methods have been applied when working to enhance the prediction accuracy of traditional statistical methods in the field of plant breeding. Although deep learning seems to be a promising approach for genomic prediction, it has proven to have some limitations, since its conventional methods fail to leverage all available information. Multimodal deep learning methods aim to improve the predictive power of their unimodal counterparts by introducing several modalities (sources) of input information. In this review, we introduce some theoretical basic concepts of multimodal deep learning and provide a list of the most widely used neural network architectures in deep learning, as well as the available strategies to fuse data from different modalities. We mention some of the available computational resources for the practical implementation of multimodal deep learning problems. We finally performed a review of applications of multimodal deep learning to genomic selection in plant breeding and other related fields. We present a meta-picture of the practical performance of multimodal deep learning methods to highlight how these tools can help address complex problems in the field of plant breeding. We discussed some relevant considerations that researchers should keep in mind when applying multimodal deep learning methods. Multimodal deep learning holds significant potential for various fields, including genomic selection. While multimodal deep learning displays enhanced prediction capabilities over unimodal deep learning and other machine learning methods, it demands more computational resources. Multimodal deep learning effectively captures intermodal interactions, especially when integrating data from different sources. To apply multimodal deep learning in genomic selection, suitable architectures and fusion strategies must be chosen. It is relevant to keep in mind that multimodal deep learning, like unimodal deep learning, is a powerful tool but should be carefully applied. Given its predictive edge over traditional methods, multimodal deep learning is valuable in addressing challenges in plant breeding and food security amid a growing global population.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584676","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}

{"title":"Megavariate Methods Capture Complex Genotype-by-Environment Interactions.","authors":"Alencar Xavier, Daniel Runcie, David Habier","doi":"10.1093/genetics/iyae179","DOIUrl":"https://doi.org/10.1093/genetics/iyae179","url":null,"abstract":"<p><p>Genomic prediction models that capture genotype-by-environment interaction are useful for predicting site-specific performance by leveraging information among related individuals and correlated environments, but implementing such models is computationally challenging. This study describes the algorithm of these scalable approaches, including two models with latent representations of genotype-by-environment interactions, namely MegaLMM and MegaSEM, and an efficient multivariate mixed model solver, namely PEGS, fitting different covariance structures (unstructured, XFA, HCS). Accuracy and runtime are benchmarked on simulated scenarios with varying numbers of genotypes and environments. MegaLMM and PEGS-based XFA and HCS models provided the highest accuracy under sparse testing with 100 testing environments. PEGS-based unstructured model was orders of magnitude faster than REML-based multivariate GBLUP while providing the same accuracy. MegaSEM provided the lowest runtime, fitting a model with 200 traits and 20,000 individuals in approximately 5 minutes, and a model with 2,000 traits and 2,000 individuals in less than 3 minutes. With the G2F data, the most accurate predictions were attained with the univariate model fitted across environments and by averaging environment-level GEBVs from models with HCS and XFA covariance structures.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576884","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}

{"title":"Leveraging a new data resource to define the response of C. neoformans to environmental signals.","authors":"Yu Sung Kang, Jeffery Jung, Holly Brown, Chase Mateusiak, Tamara L Doering, Michael R Brent","doi":"10.1093/genetics/iyae178","DOIUrl":"10.1093/genetics/iyae178","url":null,"abstract":"<p><p>Cryptococcus neoformans is an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of five signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-Seq in quadruplicate, yielding 881 RNA-Seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either CO2 or exogenous cyclic AMP (cAMP). Surprisingly, adding either of these pushes overall gene expression in the opposite direction from tissue culture media alone, even though both are required for capsule development. Another unexpected finding was that rich medium blocks capsule growth completely. Statistical analysis further revealed many genes whose expression is associated with capsule thickness; deletion of one of these significantly reduced capsule size. Beyond illuminating capsule induction, our massive, uniformly collected dataset will be a significant resource for the research community.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562981","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}

{"title":"Dominant myosin storage myopathy mutations disrupt striated muscles in Drosophila and the myosin tail-tail interactome of human cardiac thick filaments.","authors":"Meera C Viswanathan, Debabrata Dutta, William A Kronert, Kripa Chitre, Raul Padron, Roger Craig, Sanford I Bernstein, Anthony Cammarato","doi":"10.1093/genetics/iyae174","DOIUrl":"https://doi.org/10.1093/genetics/iyae174","url":null,"abstract":"<p><p>Myosin storage myopathy (MSM) is a rare skeletal muscle disorder caused by mutations in the slow muscle/β-cardiac myosin heavy chain (MHC) gene. MSM missense mutations frequently disrupt the tail's stabilizing heptad repeat motif. Disease hallmarks include subsarcolemmal hyaline-like β-MHC aggregates, muscle weakness and, occasionally, cardiomyopathy. We generated transgenic, heterozygous Drosophila to examine the dominant physiological and structural effects of the L1793P, R1845W, and E1883K MHC MSM mutations on diverse muscles. The MHC variants reduced lifespan and flight and jump abilities. Moreover, confocal and electron microscopy revealed that they provoked indirect flight muscle breaks and myofibrillar disarray/degeneration with filamentous inclusions. Incorporation of GFP-myosin enabled in situ determination of thick filament lengths, which were significantly reduced in all mutants. Semi-automated heartbeat analysis uncovered aberrant cardiac function, which worsened with age. Thus, our fly models phenocopied traits observed among MSM patients. We additionally mapped the mutations onto a recently-determined, 6Å resolution, cryo-EM structure of the human cardiac thick filament. The R1845W mutation replaces a basic arginine with a polar-neutral, bulkier tryptophan, while E1883K reverses charge at critical filament loci. Both would be expected to disrupt the core and the outer shell of the backbone structure. Replacing L1793 with a proline, a potent breaker of alpha-helices, could disturb the coiled-coil of the myosin rod and alter the tail-tail interactome. Hence, all mutations likely destabilize and weaken the filament backbone. This may trigger disease in humans, while potentially analogous perturbations are likely to yield the observed thick filament and muscle disruption in our fly models.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562980","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}

{"title":"Parental-effect gene-drive elements under partial selfing, or why do Caenorhabditis genomes have hyperdivergent regions?","authors":"Matthew V Rockman","doi":"10.1093/genetics/iyae175","DOIUrl":"10.1093/genetics/iyae175","url":null,"abstract":"<p><p>Self-fertile Caenorhabditis nematodes carry a surprising number of Medea elements, alleles that act in heterozygous mothers and cause death or developmental delay in offspring that don't inherit them. At some loci, both alleles in a cross operate as independent Medeas, affecting all the homozygous progeny of a selfing heterozygote. The genomic coincidence of Medea elements and ancient, deeply coalescing haplotypes, which pepper the otherwise homogeneous genomes of these animals, raises questions about how these apparent gene-drive elements persist for long periods of time. Here I investigate how mating system affects the evolution of Medeas, and their paternal-effect counterparts, peels. Despite an intuition that antagonistic alleles should induce balancing selection by killing homozygotes, models show that, under partial selfing, antagonistic elements experience positive frequency dependence: the common allele drives the rare one extinct, even if the rare one is more penetrant. Analytical results for the threshold frequency required for one allele to invade a population show that a very weakly penetrant allele, one whose effects would escape laboratory detection, could nevertheless prevent a much more penetrant allele from invading under high rates of selfing. Ubiquitous weak antagonistic Medeas and peels could then act as localized barriers to gene flow between populations, generating genomic islands of deep coalescence. Analysis of gene expression data, however, suggest that this cannot be the whole story. A complementary explanation is that ordinary ecological balancing selection generates ancient haplotypes on which Medeas can evolve, while high homozygosity in these selfers minimizes the role of gene drive in their evolution.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548475","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}