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Noggin proteins are multifunctional extracellular regulators of cell signaling 诺金蛋白是细胞信号传导的多功能细胞外调节因子
IF 3.3 3区 生物学
Genetics Pub Date : 2022-03-31 DOI: 10.1093/genetics/iyac049
Prashath Karunaraj, O. Tidswell, E. Duncan, M. Lovegrove, Grace Jefferies, T. K. Johnson, C. Beck, P. Dearden
{"title":"Noggin proteins are multifunctional extracellular regulators of cell signaling","authors":"Prashath Karunaraj, O. Tidswell, E. Duncan, M. Lovegrove, Grace Jefferies, T. K. Johnson, C. Beck, P. Dearden","doi":"10.1093/genetics/iyac049","DOIUrl":"https://doi.org/10.1093/genetics/iyac049","url":null,"abstract":"Abstract Noggin is an extracellular cysteine knot protein that plays a crucial role in vertebrate dorsoventral patterning. Noggin binds and inhibits the activity of bone morphogenetic proteins via a conserved N-terminal clip domain. Noncanonical orthologs of Noggin that lack a clip domain (“Noggin-like” proteins) are encoded in many arthropod genomes and are thought to have evolved into receptor tyrosine kinase ligands that promote Torso/receptor tyrosine kinase signaling rather than inhibiting bone morphogenic protein signaling. Here, we examined the molecular function of noggin/noggin-like genes (ApNL1 and ApNL2) from the arthropod pea aphid using the dorso-ventral patterning of Xenopus and the terminal patterning system of Drosophila to identify whether these proteins function as bone morphogenic protein or receptor tyrosine kinase signaling regulators. Our findings reveal that ApNL1 from the pea aphid can regulate both bone morphogenic protein and receptor tyrosine kinase signaling pathways, and unexpectedly, that the clip domain is not essential for its antagonism of bone morphogenic protein signaling. Our findings indicate that ancestral noggin/noggin-like genes were multifunctional regulators of signaling that have specialized to regulate multiple cell signaling pathways during the evolution of animals.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45771534","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
Variation in cytonuclear expression accommodation among allopolyploid plants 异源多倍体植物细胞核表达调节的变异
IF 3.3 3区 生物学
Genetics Pub Date : 2022-03-12 DOI: 10.1101/2022.03.10.483839
C. Grover, Evan S. Forsythe, Joel Sharbrough, Emma R. Miller, Justin L. Conover, R. DeTar, Carolina Chavarro, Mark A. Arick, D. Peterson, S. Leal-Bertioli, Daniel B. Sloan, J. Wendel
{"title":"Variation in cytonuclear expression accommodation among allopolyploid plants","authors":"C. Grover, Evan S. Forsythe, Joel Sharbrough, Emma R. Miller, Justin L. Conover, R. DeTar, Carolina Chavarro, Mark A. Arick, D. Peterson, S. Leal-Bertioli, Daniel B. Sloan, J. Wendel","doi":"10.1101/2022.03.10.483839","DOIUrl":"https://doi.org/10.1101/2022.03.10.483839","url":null,"abstract":"Cytonuclear coevolution is a common feature among plants, which coordinates gene expression and protein products between the nucleus and organelles. Consequently, lineage-specific differences may result in incompatibilities between the nucleus and cytoplasm in hybrid taxa. Allopolyploidy is also a common phenomenon in plant evolution. The hybrid nature of allopolyploids may result in cytonuclear incompatibilities, but the massive nuclear redundancy created during polyploidy affords additional avenues for resolving cytonuclear conflict (i.e., cytonuclear accommodation). Here we evaluate expression changes in organelle-targeted nuclear genes for six allopolyploid lineages that represent four genera (i.e., Arabidopsis, Arachis, Chenopodium, and Gossypium) and encompass a range in polyploid ages. Because incompatibilities between the nucleus and cytoplasm could potentially result in biases toward the maternal homoeolog and/or maternal expression level, we evaluate patterns of homoeolog usage, expression bias, and expression level dominance in cytonuclear genes relative to the background of non-cytonuclear expression changes and to the diploid parents. Although we find subsets of cytonuclear genes in most lineages that match our expectations of maternal preference, these observations are not consistent among either allopolyploids or categories of organelle-targeted genes. Our results indicate that cytonuclear expression accommodation may be a subtle and/or variable phenomenon that does not capture the full range of mechanisms by which allopolyploid plants resolve nuclear-cytoplasmic incompatibilities.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"222 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46998135","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: 3
Taking flight: an educational primer for use with "A novel mechanism for activation of myosin regulatory light chain by protein kinase C-delta in Drosophila". 飞行:用于“果蝇蛋白激酶C-delta激活肌球蛋白调节轻链的新机制”的教育性引物
IF 3.3 3区 生物学
Genetics Pub Date : 2022-03-03 DOI: 10.1093/genetics/iyab187
Scott J Nowak, Krista C Dobi
{"title":"Taking flight: an educational primer for use with \"A novel mechanism for activation of myosin regulatory light chain by protein kinase C-delta in Drosophila\".","authors":"Scott J Nowak, Krista C Dobi","doi":"10.1093/genetics/iyab187","DOIUrl":"10.1093/genetics/iyab187","url":null,"abstract":"<p><p>Muscles are required for animal movement, feeding, heartbeat, and reproduction. Disruption of muscle function can lead to mobility impairments and diseases like muscular dystrophy and cardiac myopathy; therefore, research in this area has significant implications for public health. Recent work by Vaziri and colleagues has taken genetic, cell biological, and biochemical approaches to identify Protein kinase C-d (Pkcδ) as a novel regulator of the essential myosin light chain 2 (MLC2) by phosphorylation. The authors determine which residues of MLC2 are modified by Pkcδ and show that phosphorylation by Pkcδ is required for proper sarcomere assembly and function. This study underscores the importance of Drosophila melanogaster as a model system for muscle function and highlights how protein phosphorylation is a vital part of post-translational gene regulation.</p>","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48855920","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
Fisher's historic 1922 paper On the dominance ratio. 费舍尔1922年的历史性论文《论优势比》
IF 3.3 3区 生物学
Genetics Pub Date : 2022-03-03 DOI: 10.1093/genetics/iyac006
Brian Charlesworth
{"title":"Fisher's historic 1922 paper On the dominance ratio.","authors":"Brian Charlesworth","doi":"10.1093/genetics/iyac006","DOIUrl":"10.1093/genetics/iyac006","url":null,"abstract":"<p><p>R.A. Fisher's 1922 paper On the dominance ratio has a strong claim to be the foundation paper for modern population genetics. It greatly influenced subsequent work by Haldane and Wright, and contributed 3 major innovations to the study of evolution at the genetic level. First, the introduction of a general model of selection at a single locus, which showed how variability could be maintained by heterozygote advantage. Second, the use of the branching process approach to show that a beneficial mutation has a substantial chance of loss from the population, even when the population size is extremely large. Third, the invention of the concept of a probability distribution of allele frequency, caused by random sampling of allele frequencies due to finite population size, and the first use of a diffusion equation to investigate the properties of such a distribution. Although Fisher was motivated by an inference that later turned out to lack strong empirical support (a substantial contribution of dominance to quantitative trait variability), and his use of a diffusion equation was marred by a technical mistake, the paper introduced concepts and methods that pervade much subsequent work in population genetics.</p>","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47270036","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
The wing imaginal disc 翅膀想象盘
IF 3.3 3区 生物学
Genetics Pub Date : 2022-02-21 DOI: 10.1093/genetics/iyac020
B. Tripathi, K. Irvine
{"title":"The wing imaginal disc","authors":"B. Tripathi, K. Irvine","doi":"10.1093/genetics/iyac020","DOIUrl":"https://doi.org/10.1093/genetics/iyac020","url":null,"abstract":"Abstract The Drosophila wing imaginal disc is a tissue of undifferentiated cells that are precursors of the wing and most of the notum of the adult fly. The wing disc first forms during embryogenesis from a cluster of ∼30 cells located in the second thoracic segment, which invaginate to form a sac-like structure. They undergo extensive proliferation during larval stages to form a mature larval wing disc of ∼35,000 cells. During this time, distinct cell fates are assigned to different regions, and the wing disc develops a complex morphology. Finally, during pupal stages the wing disc undergoes morphogenetic processes and then differentiates to form the adult wing and notum. While the bulk of the wing disc comprises epithelial cells, it also includes neurons and glia, and is associated with tracheal cells and muscle precursor cells. The relative simplicity and accessibility of the wing disc, combined with the wealth of genetic tools available in Drosophila, have combined to make it a premier system for identifying genes and deciphering systems that play crucial roles in animal development. Studies in wing imaginal discs have made key contributions to many areas of biology, including tissue patterning, signal transduction, growth control, regeneration, planar cell polarity, morphogenesis, and tissue mechanics.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"220 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43393039","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: 19
The 2021 Genetics Society of America Medal: Douglas Koshland 2021年美国遗传学会奖章:道格拉斯·科什兰
IF 3.3 3区 生物学
Genetics Pub Date : 2022-02-13 DOI: 10.1093/genetics/iyab232
D. Koshland
{"title":"The 2021 Genetics Society of America Medal: Douglas Koshland","authors":"D. Koshland","doi":"10.1093/genetics/iyab232","DOIUrl":"https://doi.org/10.1093/genetics/iyab232","url":null,"abstract":"Abstract The Genetics Society of America Medal honors an individual member of the Society for outstanding contributions to the field of genetics in the last 15 years. Genetics Society of America established the Medal in 1981 to recognize members who exemplify the ingenuity of the Genetics Society of America membership through elegant and highly meaningful contributions to modern genetics. The 2021 Genetics Society of America Medal has been awarded to Douglas Koshland of the University of California, Berkeley. His advances in chromosome biology have not only illuminated fundamental features of the structure of chromosomes but also provided tools for many others to use.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43589759","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
MOET: a web-based gene set enrichment tool at the Rat Genome Database for multiontology and multispecies analyses MOET:大鼠基因组数据库中用于多本体和多物种分析的基于网络的基因集富集工具
IF 3.3 3区 生物学
Genetics Pub Date : 2022-01-28 DOI: 10.1093/genetics/iyac005
M. Vedi, H. S. Nalabolu, Chien-Wei Lin, M. Hoffman, Jennifer R. Smith, K. Brodie, J. D. De Pons, W. Demos, A. Gibson, G. Hayman, M. L. Hill, M. Kaldunski, L. Lamers, S. Laulederkind, K. Thorat, J. Thota, M. Tutaj, M. Tutaj, Shur-Jen Wang, S. Zacher, M. Dwinell, A. Kwitek
{"title":"MOET: a web-based gene set enrichment tool at the Rat Genome Database for multiontology and multispecies analyses","authors":"M. Vedi, H. S. Nalabolu, Chien-Wei Lin, M. Hoffman, Jennifer R. Smith, K. Brodie, J. D. De Pons, W. Demos, A. Gibson, G. Hayman, M. L. Hill, M. Kaldunski, L. Lamers, S. Laulederkind, K. Thorat, J. Thota, M. Tutaj, M. Tutaj, Shur-Jen Wang, S. Zacher, M. Dwinell, A. Kwitek","doi":"10.1093/genetics/iyac005","DOIUrl":"https://doi.org/10.1093/genetics/iyac005","url":null,"abstract":"Abstract Biological interpretation of a large amount of gene or protein data is complex. Ontology analysis tools are imperative in finding functional similarities through overrepresentation or enrichment of terms associated with the input gene or protein lists. However, most tools are limited by their ability to do ontology-specific and species-limited analyses. Furthermore, some enrichment tools are not updated frequently with recent information from databases, thus giving users inaccurate, outdated or uninformative data. Here, we present MOET or the Multi-Ontology Enrichment Tool (v.1 released in April 2019 and v.2 released in May 2021), an ontology analysis tool leveraging data that the Rat Genome Database (RGD) integrated from in-house expert curation and external databases including the National Center for Biotechnology Information (NCBI), Mouse Genome Informatics (MGI), The Kyoto Encyclopedia of Genes and Genomes (KEGG), The Gene Ontology Resource, UniProt-GOA, and others. Given a gene or protein list, MOET analysis identifies significantly overrepresented ontology terms using a hypergeometric test and provides nominal and Bonferroni corrected P-values and odds ratios for the overrepresented terms. The results are shown as a downloadable list of terms with and without Bonferroni correction, and a graph of the P-values and number of annotated genes for each term in the list. MOET can be accessed freely from https://rgd.mcw.edu/rgdweb/enrichment/start.html.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43626824","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: 4
Recombination, selection, and the evolution of tandem gene arrays 串联基因阵列的重组、选择和进化
IF 3.3 3区 生物学
Genetics Pub Date : 2022-01-28 DOI: 10.1101/2022.01.26.477888
M. Otto, Yichen Zheng, T. Wiehe
{"title":"Recombination, selection, and the evolution of tandem gene arrays","authors":"M. Otto, Yichen Zheng, T. Wiehe","doi":"10.1101/2022.01.26.477888","DOIUrl":"https://doi.org/10.1101/2022.01.26.477888","url":null,"abstract":"Multi-gene families – immunity genes or sensory receptors, for instance – are often subject to diversifying selection. Allelic diversity may be favoured not only through balancing or frequency dependent selection at individual loci, but also by associating different alleles in multi copy gene families. Using a combination of analytical calculations and simulations, we explored a population genetic model of epistatic selection and unequal recombination, where a trade-off exists between the benefit of allelic diversity and the cost of copy abundance. Starting from the neutral case, where we showed that gene copy number is Gamma-distributed at equilibrium, we derived also mean and shape of the limiting distribution under selection. Considering a more general model which includes variable population size and population substructure, we explored by simulations mean fitness and some summary statistics of the copy number distribution. We determined the relative effects of selection, recombination and demographic parameters in maintaining allelic diversity and shaping mean fitness of a population. One way to control the variance of copy number is by lowering the rate of unequal recombination. Indeed, when encoding recombination by a rate modifier locus, we observe exactly this prediction. Finally, we analyzed the empirical copy number distribution of three genes in human and estimated recombination and selection parameters of our model.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44500174","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: 6
2021 GENETICS Reviewer Index 2021年遗传学审稿人索引
IF 3.3 3区 生物学
Genetics Pub Date : 2021-12-01 DOI: 10.1093/genetics/iyab200
{"title":"2021 GENETICS Reviewer Index","authors":"","doi":"10.1093/genetics/iyab200","DOIUrl":"https://doi.org/10.1093/genetics/iyab200","url":null,"abstract":"","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42110910","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
Selective Disruption of Drp1-Independent Mitophagy and Mitolysosome Trafficking by an Alzheimer's Disease Relevant Tau Modification in a Novel C. elegans Model. 在一种新的秀丽隐杆线虫模型中,与阿尔茨海默病相关的Tau修饰选择性地破坏了drp1独立的有丝分裂和有丝分裂酶体运输。
IF 3.3 3区 生物学
Genetics Pub Date : 2021-11-29 DOI: 10.21203/rs.3.rs-1096882/v1
Sanjib Guha, Anson Cheng, Trae Carroll, Dennisha King, Shon Koren, Sierra Swords, Keith Nehrke, Gail V W Johnson
{"title":"Selective Disruption of Drp1-Independent Mitophagy and Mitolysosome Trafficking by an Alzheimer's Disease Relevant Tau Modification in a Novel C. elegans Model.","authors":"Sanjib Guha, Anson Cheng, Trae Carroll, Dennisha King, Shon Koren, Sierra Swords, Keith Nehrke, Gail V W Johnson","doi":"10.21203/rs.3.rs-1096882/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-1096882/v1","url":null,"abstract":"Accumulation of inappropriately phosphorylated tau into neurofibrillary tangles (NFT) is a defining feature of Alzheimer's disease (AD), with Tau pT231 being an early harbinger of tau pathology. Previously, we demonstrated that expressing a single genomic copy of human phosphomimetic mutant tau (T231E) in C. elegans drove age-dependent neurodegeneration. A critical finding was that T231E, unlike wild type tau, completely and selectively suppressed oxidative stress-induced mitophagy. Here, we used dynamic imaging approaches to analyze T231E-associated changes in mitochondria and mitolysosome (ML) morphology, abundance, trafficking, and stress-induced mitophagy as a function of mitochondrial fission mediator Drp1, which has been demonstrated to interact with hyper phosphorylated tau and contribute to AD pathogenesis, as well as Pink1, a well-recognized mediator of mitochondrial quality control that works together with Parkin to support stress-induced mitophagy. T231E impacted both mitophagy and ML neurite trafficking with exquisite selectivity, sparing macroautophagy as well as lysosome and autolysosome trafficking. Both oxidative-stress induced mitophagy and the ability of T231E to suppress it were independent of drp-1, but at least partially dependent on pink-1. Organelle trafficking was more complicated, with drp-1 and pink-1 mutants exerting independent effects, but generally supported the idea that the mitophagy phenotype is of greater physiologic impact in T231E. Collectively, our results refine the mechanistic pathway through which T231E causes neurodegeneration, demonstrating pathologic selectivity for mutations that mimic tauopathy-associated post-translational modifications, physiologic selectivity for organelles that contain damaged mitochondria, and molecular selectivity for Drp1-independent, Pink1-dependent, perhaps adaptive, mitophagy.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42237054","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: 1
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