Pub Date : 2024-02-21DOI: 10.1093/genetics/iyae003
Vincent Garin, Chiaka Diallo, Mohamed Lamine Tékété, Korotimi Théra, Baptiste Guitton, Karim Dagno, Abdoulaye G Diallo, Mamoutou Kouressy, Willmar Leiser, Fred Rattunde, Ibrahima Sissoko, Aboubacar Touré, Baloua Nébié, Moussa Samaké, Jana Kholovà, Julien Frouin, David Pot, Michel Vaksmann, Eva Weltzien, Niaba Témé, Jean-François Rami
Identifying the genetic factors impacting the adaptation of crops to environmental conditions is of key interest for conservation and selection purposes. It can be achieved using population genomics, and evolutionary or quantitative genetics. Here we present a sorghum multireference back-cross nested association mapping population composed of 3,901 lines produced by crossing 24 diverse parents to 3 elite parents from West and Central Africa-back-cross nested association mapping. The population was phenotyped in environments characterized by differences in photoperiod, rainfall pattern, temperature levels, and soil fertility. To integrate the multiparental and multi-environmental dimension of our data we proposed a new approach for quantitative trait loci (QTL) detection and parental effect estimation. We extended our model to estimate QTL effect sensitivity to environmental covariates, which facilitated the integration of envirotyping data. Our models allowed spatial projections of the QTL effects in agro-ecologies of interest. We utilized this strategy to analyze the genetic architecture of flowering time and plant height, which represents key adaptation mechanisms in environments like West Africa. Our results allowed a better characterization of well-known genomic regions influencing flowering time concerning their response to photoperiod with Ma6 and Ma1 being photoperiod-sensitive and the region of possible candidate gene Elf3 being photoperiod-insensitive. We also accessed a better understanding of plant height genetic determinism with the combined effects of phenology-dependent (Ma6) and independent (qHT7.1 and Dw3) genomic regions. Therefore, we argue that the West and Central Africa-back-cross nested association mapping and the presented analytical approach constitute unique resources to better understand adaptation in sorghum with direct application to develop climate-smart varieties.
{"title":"Characterization of adaptation mechanisms in sorghum using a multireference back-cross nested association mapping design and envirotyping.","authors":"Vincent Garin, Chiaka Diallo, Mohamed Lamine Tékété, Korotimi Théra, Baptiste Guitton, Karim Dagno, Abdoulaye G Diallo, Mamoutou Kouressy, Willmar Leiser, Fred Rattunde, Ibrahima Sissoko, Aboubacar Touré, Baloua Nébié, Moussa Samaké, Jana Kholovà, Julien Frouin, David Pot, Michel Vaksmann, Eva Weltzien, Niaba Témé, Jean-François Rami","doi":"10.1093/genetics/iyae003","DOIUrl":"https://doi.org/10.1093/genetics/iyae003","url":null,"abstract":"Identifying the genetic factors impacting the adaptation of crops to environmental conditions is of key interest for conservation and selection purposes. It can be achieved using population genomics, and evolutionary or quantitative genetics. Here we present a sorghum multireference back-cross nested association mapping population composed of 3,901 lines produced by crossing 24 diverse parents to 3 elite parents from West and Central Africa-back-cross nested association mapping. The population was phenotyped in environments characterized by differences in photoperiod, rainfall pattern, temperature levels, and soil fertility. To integrate the multiparental and multi-environmental dimension of our data we proposed a new approach for quantitative trait loci (QTL) detection and parental effect estimation. We extended our model to estimate QTL effect sensitivity to environmental covariates, which facilitated the integration of envirotyping data. Our models allowed spatial projections of the QTL effects in agro-ecologies of interest. We utilized this strategy to analyze the genetic architecture of flowering time and plant height, which represents key adaptation mechanisms in environments like West Africa. Our results allowed a better characterization of well-known genomic regions influencing flowering time concerning their response to photoperiod with Ma6 and Ma1 being photoperiod-sensitive and the region of possible candidate gene Elf3 being photoperiod-insensitive. We also accessed a better understanding of plant height genetic determinism with the combined effects of phenology-dependent (Ma6) and independent (qHT7.1 and Dw3) genomic regions. Therefore, we argue that the West and Central Africa-back-cross nested association mapping and the presented analytical approach constitute unique resources to better understand adaptation in sorghum with direct application to develop climate-smart varieties.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"148 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918799","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}
Pub Date : 2024-02-01DOI: 10.1093/genetics/iyae009
Hunter C Herriage, Brian R Calvi
Endocycling cells grow and repeatedly duplicate their genome without dividing. Cells switch from mitotic cycles to endocycles in response to developmental signals during the growth of specific tissues in a wide range of organisms. The purpose of switching to endocycles, however, remains unclear in many tissues. Additionally, cells can switch to endocycles in response to conditional signals, which can have beneficial or pathological effects on tissues. However, the impact of these unscheduled endocycles on development is underexplored. Here, we use Drosophila ovarian somatic follicle cells as a model to examine the impact of unscheduled endocycles on tissue growth and function. Follicle cells normally switch to endocycles at mid-oogenesis. Inducing follicle cells to prematurely switch to endocycles resulted in lethality of the resulting embryos. Analysis of ovaries with premature follicle cell endocycles revealed aberrant follicular epithelial structure and pleiotropic defects in oocyte growth, developmental gene amplification, and the migration of a special set of follicle cells known as border cells. Overall, these findings reveal how unscheduled endocycles can disrupt tissue growth and function to cause aberrant development.
{"title":"Premature endocycling of Drosophila follicle cells causes pleiotropic defects in oogenesis.","authors":"Hunter C Herriage, Brian R Calvi","doi":"10.1093/genetics/iyae009","DOIUrl":"https://doi.org/10.1093/genetics/iyae009","url":null,"abstract":"Endocycling cells grow and repeatedly duplicate their genome without dividing. Cells switch from mitotic cycles to endocycles in response to developmental signals during the growth of specific tissues in a wide range of organisms. The purpose of switching to endocycles, however, remains unclear in many tissues. Additionally, cells can switch to endocycles in response to conditional signals, which can have beneficial or pathological effects on tissues. However, the impact of these unscheduled endocycles on development is underexplored. Here, we use Drosophila ovarian somatic follicle cells as a model to examine the impact of unscheduled endocycles on tissue growth and function. Follicle cells normally switch to endocycles at mid-oogenesis. Inducing follicle cells to prematurely switch to endocycles resulted in lethality of the resulting embryos. Analysis of ovaries with premature follicle cell endocycles revealed aberrant follicular epithelial structure and pleiotropic defects in oocyte growth, developmental gene amplification, and the migration of a special set of follicle cells known as border cells. Overall, these findings reveal how unscheduled endocycles can disrupt tissue growth and function to cause aberrant development.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"5 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668899","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}
Pub Date : 2024-02-01DOI: 10.1093/genetics/iyad211
Arzu Öztürk-Çolak, Steven J Marygold, Giulia Antonazzo, Helen Attrill, Damien Goutte-Gattat, Victoria K Jenkins, Beverley B Matthews, Gillian Millburn, Gilberto Dos Santos, Christopher J Tabone
FlyBase (flybase.org) is a model organism database and knowledge base about Drosophila melanogaster, commonly known as the fruit fly. Researchers from around the world rely on the genetic, genomic, and functional information available in FlyBase, as well as its tools to view and interrogate these data. In this article, we describe the latest developments and updates to FlyBase. These include the introduction of single-cell RNA sequencing data, improved content and display of functional information, updated orthology pipelines, new chemical reports, and enhancements to our outreach resources.
{"title":"FlyBase: updates to the Drosophila genes and genomes database.","authors":"Arzu Öztürk-Çolak, Steven J Marygold, Giulia Antonazzo, Helen Attrill, Damien Goutte-Gattat, Victoria K Jenkins, Beverley B Matthews, Gillian Millburn, Gilberto Dos Santos, Christopher J Tabone","doi":"10.1093/genetics/iyad211","DOIUrl":"https://doi.org/10.1093/genetics/iyad211","url":null,"abstract":"FlyBase (flybase.org) is a model organism database and knowledge base about Drosophila melanogaster, commonly known as the fruit fly. Researchers from around the world rely on the genetic, genomic, and functional information available in FlyBase, as well as its tools to view and interrogate these data. In this article, we describe the latest developments and updates to FlyBase. These include the introduction of single-cell RNA sequencing data, improved content and display of functional information, updated orthology pipelines, new chemical reports, and enhancements to our outreach resources.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"9 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669566","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}
The nuclear pore complex (NPC) mediates the selective exchange of macromolecules between the nucleus and the cytoplasm. Neurodegenerative diseases such as amyotrophic lateral sclerosis are characterized by mislocalization of nucleoporins (Nups), transport receptors, and Ras-related nuclear proteins into nucleoplasmic or cytosolic aggregates, underscoring the importance of precise assembly of the NPC. The assembly state of large protein complexes is strictly monitored by the protein quality control system. The ubiquitin-proteasome system may eliminate aberrant, misfolded, and/or orphan components; however, the involvement of the ubiquitin-proteasome system in the degradation of non-native Nups in the NPC remains unclear. Here, we show that in Saccharomyces cerevisiae, although Nup1 (the FG-nucleoporin component of the central core of the NPC) was stable, C-terminally green fluorescent protein (GFP)-tagged Nup1, which had been incorporated into the NPC, was degraded by the proteasome especially under heat stress conditions. The degradation was dependent on the San1 ubiquitin ligase and Cdc48/p97, as well as its cofactor Doa1. We also demonstrate that San1 weakly but certainly contributes to the degradation of non-tagged endogenous Nup1 in cells defective in NPC biogenesis by the deletion of NUP120. In addition, the overexpression of SAN1 exacerbated the growth defect phenotype of nup120Δ cells, which may be caused by excess degradation of defective Nups due to the deletion of NUP120. These biochemical and genetic data suggest that San1 is involved in the degradation of non-native nucleoporins generated by genetic mutation or when NPC biogenesis is impaired.
{"title":"Role of the San1 ubiquitin ligase in the heat stress-induced degradation of non-native Nup1 in the nuclear pore complex.","authors":"Takanari Ikeda, Kenji Yamazaki, Fumihiko Okumura, Takumi Kamura, Kunio Nakatsukasa","doi":"10.1093/genetics/iyae017","DOIUrl":"https://doi.org/10.1093/genetics/iyae017","url":null,"abstract":"The nuclear pore complex (NPC) mediates the selective exchange of macromolecules between the nucleus and the cytoplasm. Neurodegenerative diseases such as amyotrophic lateral sclerosis are characterized by mislocalization of nucleoporins (Nups), transport receptors, and Ras-related nuclear proteins into nucleoplasmic or cytosolic aggregates, underscoring the importance of precise assembly of the NPC. The assembly state of large protein complexes is strictly monitored by the protein quality control system. The ubiquitin-proteasome system may eliminate aberrant, misfolded, and/or orphan components; however, the involvement of the ubiquitin-proteasome system in the degradation of non-native Nups in the NPC remains unclear. Here, we show that in Saccharomyces cerevisiae, although Nup1 (the FG-nucleoporin component of the central core of the NPC) was stable, C-terminally green fluorescent protein (GFP)-tagged Nup1, which had been incorporated into the NPC, was degraded by the proteasome especially under heat stress conditions. The degradation was dependent on the San1 ubiquitin ligase and Cdc48/p97, as well as its cofactor Doa1. We also demonstrate that San1 weakly but certainly contributes to the degradation of non-tagged endogenous Nup1 in cells defective in NPC biogenesis by the deletion of NUP120. In addition, the overexpression of SAN1 exacerbated the growth defect phenotype of nup120Δ cells, which may be caused by excess degradation of defective Nups due to the deletion of NUP120. These biochemical and genetic data suggest that San1 is involved in the degradation of non-native nucleoporins generated by genetic mutation or when NPC biogenesis is impaired.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"11 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669041","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}
Pub Date : 2023-12-20DOI: 10.1093/genetics/iyad214
Suman Dash, Sameer Joshi, Ajith V Pankajam, Akira Shinohara, Koodali T Nishant
Meiotic crossovers are initiated from programmed DNA Double Strand Breaks (DSBs). The Msh4-Msh5 heterodimer is an evolutionarily conserved mismatch repair related protein complex that promotes meiotic crossovers by stabilizing strand invasion intermediates and joint molecule structures such as Holliday junctions. In vivo studies using homozygous strains of the baker's yeast Saccharomyces cerevisiae (SK1) show that the Msh4-Msh5 complex associates with DSB hotspots, chromosome axes, and centromeres. Many organisms have heterozygous genomes that can affect the stability of strand invasion intermediates through heteroduplex rejection of mismatch containing sequences. To examine Msh4-Msh5 function in a heterozygous context, we performed ChIP-Seq analysis in a rapidly sporulating hybrid S. cerevisiae strain (S288c-sp/YJM789, containing sporulation enhancing QTLs from SK1), using SNP information to distinguish reads from homologous chromosomes. Overall, Msh5 localization in this hybrid strain was similar to that determined in the homozygous strain (SK1). However, relative Msh5 levels were reduced in regions of high heterozygosity, suggesting that high mismatch densities reduce levels of recombination intermediates to which Msh4-Msh5 binds. Msh5 peaks were also wider in the hybrid background compared to the homozygous strain (SK1). We determined regions containing heteroduplex DNA by detecting chimeric sequence reads with SNPs from both parents. Msh5 bound DSB hotspots overlap with regions that have chimeric DNA, consistent with Msh5 binding to heteroduplex-containing recombination intermediates.
减数分裂交叉是由程序DNA双链断裂（DSB）启动的。Msh4-Msh5异源二聚体是一种进化保守的错配修复相关蛋白复合物，它通过稳定链侵入中间体和霍利迪连接等联合分子结构来促进减数分裂交叉。利用面包酵母 Saccharomyces cerevisiae（SK1）的同基因株进行的体内研究表明，Msh4-Msh5 复合物与 DSB 热点、染色体轴和中心粒相关联。许多生物都有杂合基因组，这些杂合基因组会通过含有错配序列的杂合双链排斥作用影响链侵入中间体的稳定性。为了研究杂合背景下 Msh4-Msh5 的功能，我们在快速孢子化杂交 S. cerevisiae 菌株（S288c-sp/YJM789，含有来自 SK1 的孢子化增强 QTLs）中进行了 ChIP-Seq 分析，使用 SNP 信息来区分来自同源染色体的读数。总体而言，该杂交品系中的 Msh5 定位与同源品系（SK1）中的定位相似。然而，在高杂合度区域，Msh5 的相对水平降低了，这表明高错配密度降低了与 Msh4-Msh5 结合的重组中间体的水平。与同源株（SK1）相比，杂交背景中的 Msh5 峰值也更宽。我们通过检测含有双亲 SNP 的嵌合序列读数，确定了含有异源双链 DNA 的区域。Msh5结合的DSB热点与含有嵌合DNA的区域重叠，这与Msh5结合到含有杂合双链的重组中间体是一致的。
{"title":"Heterozygosity alters Msh5 binding to meiotic chromosomes in the baker's yeast.","authors":"Suman Dash, Sameer Joshi, Ajith V Pankajam, Akira Shinohara, Koodali T Nishant","doi":"10.1093/genetics/iyad214","DOIUrl":"https://doi.org/10.1093/genetics/iyad214","url":null,"abstract":"Meiotic crossovers are initiated from programmed DNA Double Strand Breaks (DSBs). The Msh4-Msh5 heterodimer is an evolutionarily conserved mismatch repair related protein complex that promotes meiotic crossovers by stabilizing strand invasion intermediates and joint molecule structures such as Holliday junctions. In vivo studies using homozygous strains of the baker's yeast Saccharomyces cerevisiae (SK1) show that the Msh4-Msh5 complex associates with DSB hotspots, chromosome axes, and centromeres. Many organisms have heterozygous genomes that can affect the stability of strand invasion intermediates through heteroduplex rejection of mismatch containing sequences. To examine Msh4-Msh5 function in a heterozygous context, we performed ChIP-Seq analysis in a rapidly sporulating hybrid S. cerevisiae strain (S288c-sp/YJM789, containing sporulation enhancing QTLs from SK1), using SNP information to distinguish reads from homologous chromosomes. Overall, Msh5 localization in this hybrid strain was similar to that determined in the homozygous strain (SK1). However, relative Msh5 levels were reduced in regions of high heterozygosity, suggesting that high mismatch densities reduce levels of recombination intermediates to which Msh4-Msh5 binds. Msh5 peaks were also wider in the hybrid background compared to the homozygous strain (SK1). We determined regions containing heteroduplex DNA by detecting chimeric sequence reads with SNPs from both parents. Msh5 bound DSB hotspots overlap with regions that have chimeric DNA, consistent with Msh5 binding to heteroduplex-containing recombination intermediates.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826674","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}
Pub Date : 2023-12-20DOI: 10.1093/genetics/iyad200
Takuya Akiyama, Laurel A Raftery, Kristi A Wharton
In the mid-1960s, bone morphogenetic proteins (BMPs) were first identified in the extracts of bone to have the remarkable ability to induce heterotopic bone. When the Drosophila gene decapentaplegic (dpp) was first identified to share sequence similarity with mammalian BMP2/BMP4 in the late-1980s, it became clear that secreted BMP ligands can mediate processes other than bone formation. Following this discovery, collaborative efforts between Drosophila geneticists and mammalian biochemists made use of the strengths of their respective model systems to identify BMP signaling components and delineate the pathway. The ability to conduct genetic modifier screens in Drosophila with relative ease was critical in identifying the intracellular signal transducers for BMP signaling and the related transforming growth factor-beta/activin signaling pathway. Such screens also revealed a host of genes that encode other core signaling components and regulators of the pathway. In this review, we provide a historical account of this exciting time of gene discovery and discuss how the field has advanced over the past 30 years. We have learned that while the core BMP pathway is quite simple, composed of 3 components (ligand, receptor, and signal transducer), behind the versatility of this pathway lies multiple layers of regulation that ensures precise tissue-specific signaling output. We provide a sampling of these discoveries and highlight many questions that remain to be answered to fully understand the complexity of BMP signaling.
{"title":"Bone morphogenetic protein signaling: the pathway and its regulation.","authors":"Takuya Akiyama, Laurel A Raftery, Kristi A Wharton","doi":"10.1093/genetics/iyad200","DOIUrl":"https://doi.org/10.1093/genetics/iyad200","url":null,"abstract":"In the mid-1960s, bone morphogenetic proteins (BMPs) were first identified in the extracts of bone to have the remarkable ability to induce heterotopic bone. When the Drosophila gene decapentaplegic (dpp) was first identified to share sequence similarity with mammalian BMP2/BMP4 in the late-1980s, it became clear that secreted BMP ligands can mediate processes other than bone formation. Following this discovery, collaborative efforts between Drosophila geneticists and mammalian biochemists made use of the strengths of their respective model systems to identify BMP signaling components and delineate the pathway. The ability to conduct genetic modifier screens in Drosophila with relative ease was critical in identifying the intracellular signal transducers for BMP signaling and the related transforming growth factor-beta/activin signaling pathway. Such screens also revealed a host of genes that encode other core signaling components and regulators of the pathway. In this review, we provide a historical account of this exciting time of gene discovery and discuss how the field has advanced over the past 30 years. We have learned that while the core BMP pathway is quite simple, composed of 3 components (ligand, receptor, and signal transducer), behind the versatility of this pathway lies multiple layers of regulation that ensures precise tissue-specific signaling output. We provide a sampling of these discoveries and highlight many questions that remain to be answered to fully understand the complexity of BMP signaling.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"238 1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823983","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}
Pub Date : 2023-12-20DOI: 10.1093/genetics/iyad213
P Jane Yeadon, Frederick J Bowring, David E A Catcheside
Genes regulating recombination in specific chromosomal intervals of Neurospora crassa were described in the 1960s but the mechanism is still unknown. For each of the rec-1, rec-2 and rec-3 genes, a single copy of the putative dominant allele, for example rec-2SL found in St Lawrence OR74 A wild type, reduces recombination in chromosomal regions specific to that gene. However, when we sequenced the recessive allele, rec-2LG (derived from the Lindegren 1A wild type) we found that a 10 kb region in rec-2SL strains was replaced by a 2.7 kb unrelated sequence, making the "alleles" idiomorphs. When we introduced sad-1, a mutant lacking the RNA-dependent RNA polymerase that silences unpaired coding regions during meiosis into crosses heterozygous rec-2SL/rec-2LG, it increased recombination, indicating that meiotic silencing of a gene promoting recombination is responsible for dominant suppression of recombination. Consistent with this, mutation of rec-2LG by RIP (Repeat-Induced Point mutation) generated an allele with multiple stop codons in the predicted rec-2 gene, which does not promote recombination and is recessive to rec-2LG. Sad-1 also relieves suppression of recombination in relevant target regions, in crosses heterozygous for rec-1 alleles and in crosses heterozygous for rec-3 alleles. We conclude that for all three known rec genes, one allele appears dominant only because meiotic silencing prevents the product of the active, "recessive", allele from stimulating recombination during meiosis. In addition, the proposed amino acid sequence of REC-2 suggests that regulation of recombination in Neurospora differs from any currently known mechanism.
{"title":"Recombination hotspots in Neurospora crassa controlled by idiomorphic sequences and meiotic silencing.","authors":"P Jane Yeadon, Frederick J Bowring, David E A Catcheside","doi":"10.1093/genetics/iyad213","DOIUrl":"https://doi.org/10.1093/genetics/iyad213","url":null,"abstract":"Genes regulating recombination in specific chromosomal intervals of Neurospora crassa were described in the 1960s but the mechanism is still unknown. For each of the rec-1, rec-2 and rec-3 genes, a single copy of the putative dominant allele, for example rec-2SL found in St Lawrence OR74 A wild type, reduces recombination in chromosomal regions specific to that gene. However, when we sequenced the recessive allele, rec-2LG (derived from the Lindegren 1A wild type) we found that a 10 kb region in rec-2SL strains was replaced by a 2.7 kb unrelated sequence, making the \"alleles\" idiomorphs. When we introduced sad-1, a mutant lacking the RNA-dependent RNA polymerase that silences unpaired coding regions during meiosis into crosses heterozygous rec-2SL/rec-2LG, it increased recombination, indicating that meiotic silencing of a gene promoting recombination is responsible for dominant suppression of recombination. Consistent with this, mutation of rec-2LG by RIP (Repeat-Induced Point mutation) generated an allele with multiple stop codons in the predicted rec-2 gene, which does not promote recombination and is recessive to rec-2LG. Sad-1 also relieves suppression of recombination in relevant target regions, in crosses heterozygous for rec-1 alleles and in crosses heterozygous for rec-3 alleles. We conclude that for all three known rec genes, one allele appears dominant only because meiotic silencing prevents the product of the active, \"recessive\", allele from stimulating recombination during meiosis. In addition, the proposed amino acid sequence of REC-2 suggests that regulation of recombination in Neurospora differs from any currently known mechanism.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"9 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824888","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}
Pub Date : 2023-12-12DOI: 10.1093/genetics/iyad210
Tianjing Zhao, Fangyi Wang, Richard Mott, Jack Dekkers, Hao Cheng
To adhere to and capitalize on the benefits of the FAIR (Findable, Accessible, Interoperable and Reusable) principles in agricultural genome-to-phenome studies, it is crucial to address privacy and intellectual property issues that prevent sharing and reuse of data in research and industry. Direct sharing of genotype and phenotype data is often prohibited due to intellectual property and privacy concerns. Thus there is a pressing need for encryption methods that obscure confidential aspects of the data, without affecting the outcomes of certain statistical analyses. A homomorphic encryption method for genotypes and phenotypes (HEGP) has been proposed for single-marker regression in genome-wide association studies using linear mixed models with Gaussian errors. This methodology permits frequentist likelihood-based parameter estimation and inference. In this paper, we extend HEGP to broader applications in genome-to-phenome analyses. We show that HEGP is suited to commonly used linear mixed models for genetic analyses of quantitative traits including GBLUP and RR-BLUP, as well as Bayesian variable selection methods (e.g., those in Bayesian Alphabet), for genetic parameter estimation, genomic prediction, and genome-wide association studies. By advancing the capabilities of HEGP, we offer researchers and industry professionals a secure and efficient approach for collaborative genomic analyses while preserving data confidentiality.
{"title":"Using encrypted genotypes and phenotypes for collaborative genomic analyses to maintain data confidentiality.","authors":"Tianjing Zhao, Fangyi Wang, Richard Mott, Jack Dekkers, Hao Cheng","doi":"10.1093/genetics/iyad210","DOIUrl":"https://doi.org/10.1093/genetics/iyad210","url":null,"abstract":"To adhere to and capitalize on the benefits of the FAIR (Findable, Accessible, Interoperable and Reusable) principles in agricultural genome-to-phenome studies, it is crucial to address privacy and intellectual property issues that prevent sharing and reuse of data in research and industry. Direct sharing of genotype and phenotype data is often prohibited due to intellectual property and privacy concerns. Thus there is a pressing need for encryption methods that obscure confidential aspects of the data, without affecting the outcomes of certain statistical analyses. A homomorphic encryption method for genotypes and phenotypes (HEGP) has been proposed for single-marker regression in genome-wide association studies using linear mixed models with Gaussian errors. This methodology permits frequentist likelihood-based parameter estimation and inference. In this paper, we extend HEGP to broader applications in genome-to-phenome analyses. We show that HEGP is suited to commonly used linear mixed models for genetic analyses of quantitative traits including GBLUP and RR-BLUP, as well as Bayesian variable selection methods (e.g., those in Bayesian Alphabet), for genetic parameter estimation, genomic prediction, and genome-wide association studies. By advancing the capabilities of HEGP, we offer researchers and industry professionals a secure and efficient approach for collaborative genomic analyses while preserving data confidentiality.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"123 3 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692849","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}
Pub Date : 2023-12-11DOI: 10.1093/genetics/iyad209
Hillel T Schwartz, Chieh-Hsiang Tan, Jackeline Peraza, Krystal Louise T Raymundo, Paul W Sternberg
The entomopathogenic nematode Steinernema hermaphroditum was recently rediscovered and is being developed as a genetically tractable experimental system for the study of previously unexplored biology, including parasitism of its insect hosts and mutualism with its bacterial endosymbiont Xenorhabdus griffiniae. Through whole-genome re-sequencing and genetic mapping we have for the first time molecularly identified the gene responsible for a mutationally defined phenotypic locus in an entomopathogenic nematode. In the process we observed an unexpected mutational spectrum following EMS mutagenesis in this species. We find that the ortholog of the essential C. elegans peroxidase gene skpo-2 controls body size and shape in S. hermaphroditum. We confirmed this identification by generating additional loss-of-function mutations in the gene using CRISPR-Cas9. We propose that the identification of skpo-2 will accelerate gene targeting in other Steinernema entomopathogenic nematodes used commercially in pest control, as skpo-2 is X-linked and males hemizygous for loss of its function can mate, making skpo-2 an easily recognized and maintained marker for use in co-CRISPR.
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Pub Date : 2023-12-08DOI: 10.1093/genetics/iyad208
John M Urban, Jack R Bateman, Kodie R Garza, Julia Borden, Jaison Jain, Alexia Brown, Bethany J Thach, Jacob E Bliss, Susan A Gerbi
The level of resistance to radiation and the developmental and molecular responses can vary between species, and even between developmental stages of one species. For flies (Order: Diptera), prior studies concluded that the fungus gnat Bradysia (Sciara) coprophila (sub-order: Nematocera) is more resistant to irradiation-induced mutations that cause visible phenotypes than the fruit fly Drosophila melanogaster (sub-order: Brachycera). Therefore, we characterized the effects of and level of resistance to ionizing radiation on B. coprophila throughout its life cycle. Our data show that B. coprophila embryos are highly sensitive to even low doses of gamma-irradiation, whereas late-stage larvae can tolerate up to 80 Gy (compared to 40 Gy for D. melanogaster) and still retain their ability to develop to adulthood, though with a developmental delay. To survey the genes involved in the early transcriptional response to irradiation of B. coprophila larvae, we compared larval RNA-seq profiles with and without radiation treatment. The up-regulated genes were enriched for DNA damage response genes, including those involved in DNA repair, cell cycle arrest, and apoptosis, whereas the down-regulated genes were enriched for developmental regulators, consistent with the developmental delay of irradiated larvae. Interestingly, members of the PARP and AGO families were highly upregulated in the B. coprophila radiation response. We compared the transcriptome responses in B. coprophila to the transcriptome responses in D. melanogaster from three previous studies: whereas pathway responses are highly conserved, specific gene responses are less so. Our study lays the groundwork for future work on the radiation responses in Diptera.
不同物种，甚至同一物种的不同发育阶段，对辐射的抗性水平以及发育和分子反应都可能不同。对于苍蝇（目：双翅目），先前的研究认为，与果蝇黑腹果蝇（亚目：Brachycera）相比，真菌蚋 Bradysia (Sciara) coprophila（亚目：Nematocera）对辐照诱导的突变具有更强的抵抗力，这些突变会导致明显的表型。因此，我们研究了整个生命周期中电离辐射对椰子果蝇的影响和抗性水平。我们的数据显示，B. coprophila 胚胎对低剂量的伽马辐照也高度敏感，而晚期幼虫可耐受高达 80 Gy 的辐照（D. melanogaster 的耐受量为 40 Gy），并仍能发育至成年，但发育延迟。为了调查参与B. coprophila幼虫对辐照的早期转录反应的基因，我们比较了经过和未经过辐照处理的幼虫RNA-seq图谱。上调基因富集于DNA损伤应答基因，包括参与DNA修复、细胞周期停滞和细胞凋亡的基因，而下调基因富集于发育调节因子，这与辐照幼虫的发育延迟一致。有趣的是，PARP 和 AGO 家族的成员在 B. coprophila 辐射反应中高度上调。我们将 B. coprophila 的转录组反应与之前三项研究中 D. melanogaster 的转录组反应进行了比较：虽然途径反应高度一致，但特定基因的反应却不那么一致。我们的研究为今后研究双翅目昆虫的辐射反应奠定了基础。
{"title":"Bradysia (Sciara) coprophila larvae up-regulate DNA repair pathways and down-regulate developmental regulators in response to ionizing radiation.","authors":"John M Urban, Jack R Bateman, Kodie R Garza, Julia Borden, Jaison Jain, Alexia Brown, Bethany J Thach, Jacob E Bliss, Susan A Gerbi","doi":"10.1093/genetics/iyad208","DOIUrl":"https://doi.org/10.1093/genetics/iyad208","url":null,"abstract":"The level of resistance to radiation and the developmental and molecular responses can vary between species, and even between developmental stages of one species. For flies (Order: Diptera), prior studies concluded that the fungus gnat Bradysia (Sciara) coprophila (sub-order: Nematocera) is more resistant to irradiation-induced mutations that cause visible phenotypes than the fruit fly Drosophila melanogaster (sub-order: Brachycera). Therefore, we characterized the effects of and level of resistance to ionizing radiation on B. coprophila throughout its life cycle. Our data show that B. coprophila embryos are highly sensitive to even low doses of gamma-irradiation, whereas late-stage larvae can tolerate up to 80 Gy (compared to 40 Gy for D. melanogaster) and still retain their ability to develop to adulthood, though with a developmental delay. To survey the genes involved in the early transcriptional response to irradiation of B. coprophila larvae, we compared larval RNA-seq profiles with and without radiation treatment. The up-regulated genes were enriched for DNA damage response genes, including those involved in DNA repair, cell cycle arrest, and apoptosis, whereas the down-regulated genes were enriched for developmental regulators, consistent with the developmental delay of irradiated larvae. Interestingly, members of the PARP and AGO families were highly upregulated in the B. coprophila radiation response. We compared the transcriptome responses in B. coprophila to the transcriptome responses in D. melanogaster from three previous studies: whereas pathway responses are highly conserved, specific gene responses are less so. Our study lays the groundwork for future work on the radiation responses in Diptera.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"23 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138563894","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}
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