Pub Date : 2024-08-07DOI: 10.1093/genetics/iyae090
Haolong Wang, Baofeng Su, Ying Zhang, Mei Shang, Shangjia Li, De Xing, Jinhai Wang, Logan Bern, Andrew Johnson, Jacob Al-Armanazi, Tasnuba Hasin, Darshika Hettiarachchi, Abel Paladines Parrales, Hamza Dilawar, Timothy J Bruce, Rex A Dunham, Xu Wang
In F1 hybrids, phenotypic values are expected to be near the parental means under additive effects or close to one parent under dominance. However, F1 traits can fall outside the parental range, and outbreeding depression occurs when inferior fitness is observed in hybrids. Another possible outcome is heterosis, a phenomenon that interspecific hybrids or intraspecific crossbred F1s exhibit improved fitness compared to both parental species or strains. As an application of heterosis, hybrids between channel catfish females and blue catfish males are superior in feed conversion efficiency, carcass yield, and harvestability. Over 20 years of hybrid catfish production in experimental settings and farming practices generated abundant phenotypic data, making it an ideal system to investigate heterosis. In this study, we characterized fitness in terms of growth and survival longitudinally, revealing environment-dependent heterosis. In ponds, hybrids outgrow both parents due to an extra rapid growth phase of 2-4 months in year 2. This bimodal growth pattern is unique to F1 hybrids in pond culture environments only. In sharp contrast, the same genetic types cultured in tanks display outbreeding depression, where hybrids perform poorly, while channel catfish demonstrate superiority in growth throughout development. Our findings represent the first example, known to the authors, of opposite fitness shifts in response to environmental changes in interspecific vertebrate hybrids, suggesting a broader fitness landscape for F1 hybrids. Future genomic studies based on this experiment will help understand genome-environment interaction in shaping the F1 progeny fitness in the scenario of environment-dependent heterosis and outbreeding depression.
在 F1 代杂交种中,在加性效应下,表型值应接近亲本平均值;在显性效应下,表型值应接近亲本之一。然而,F1 的性状可能会超出亲本的范围,当观察到杂种的适应性较差时,就会出现外交抑制。另一种可能的结果是异交,即种间杂交种或种内杂交 F1 与亲本物种或品系相比表现出更高的适应性。作为杂交的一种应用,渠道鲶雌鱼和蓝鲶雄鱼的杂交种在饲料转化效率、胴体产量和可收获性方面都更胜一筹。二十多年的杂交鲶鱼生产实验和养殖实践产生了丰富的表型数据,使其成为研究异质性的理想系统。在这项研究中,我们从生长和存活率的角度对适应性进行了纵向描述,揭示了依赖环境的异质性。在池塘中,由于第 2 年有 2∼4 个月的快速生长期,杂交种的生长速度超过亲本。这种双峰生长模式仅在池塘养殖环境中的 F1 代杂交种中出现。与此形成鲜明对比的是,在水箱中养殖的相同基因类型会出现近亲繁殖抑制现象,即杂交种表现不佳,而沟鲶在整个发育过程中都表现出生长优势。据作者所知,我们的研究结果是种间脊椎动物杂交种对环境变化做出相反适应性转变的第一个例子,这表明 F1 杂交种的适应性前景更为广阔。基于该实验的未来基因组研究将有助于了解基因组与环境在依赖环境的异质性和外交抑制情况下在塑造 F1 后代适应性方面的相互作用。
{"title":"From heterosis to outbreeding depression: genotype-by-environment interaction shifts hybrid fitness in opposite directions.","authors":"Haolong Wang, Baofeng Su, Ying Zhang, Mei Shang, Shangjia Li, De Xing, Jinhai Wang, Logan Bern, Andrew Johnson, Jacob Al-Armanazi, Tasnuba Hasin, Darshika Hettiarachchi, Abel Paladines Parrales, Hamza Dilawar, Timothy J Bruce, Rex A Dunham, Xu Wang","doi":"10.1093/genetics/iyae090","DOIUrl":"10.1093/genetics/iyae090","url":null,"abstract":"<p><p>In F1 hybrids, phenotypic values are expected to be near the parental means under additive effects or close to one parent under dominance. However, F1 traits can fall outside the parental range, and outbreeding depression occurs when inferior fitness is observed in hybrids. Another possible outcome is heterosis, a phenomenon that interspecific hybrids or intraspecific crossbred F1s exhibit improved fitness compared to both parental species or strains. As an application of heterosis, hybrids between channel catfish females and blue catfish males are superior in feed conversion efficiency, carcass yield, and harvestability. Over 20 years of hybrid catfish production in experimental settings and farming practices generated abundant phenotypic data, making it an ideal system to investigate heterosis. In this study, we characterized fitness in terms of growth and survival longitudinally, revealing environment-dependent heterosis. In ponds, hybrids outgrow both parents due to an extra rapid growth phase of 2-4 months in year 2. This bimodal growth pattern is unique to F1 hybrids in pond culture environments only. In sharp contrast, the same genetic types cultured in tanks display outbreeding depression, where hybrids perform poorly, while channel catfish demonstrate superiority in growth throughout development. Our findings represent the first example, known to the authors, of opposite fitness shifts in response to environmental changes in interspecific vertebrate hybrids, suggesting a broader fitness landscape for F1 hybrids. Future genomic studies based on this experiment will help understand genome-environment interaction in shaping the F1 progeny fitness in the scenario of environment-dependent heterosis and outbreeding depression.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162728","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 : 2024-08-07DOI: 10.1093/genetics/iyae101
Mitsutoshi Nakamura, Susan M Parkhurst
To survive daily damage, the formation of actomyosin ring at the wound edge is required to rapidly close cell wounds. Calcium influx is one of the start signals for these cell wound repair events. Here, we find that the rapid recruitment of all 3 Drosophila calcium-responding and phospholipid-binding Annexin proteins (AnxB9, AnxB10, and AnxB11) to distinct regions around the wound is regulated by the quantity of calcium influx rather than their binding to specific phospholipids. The distinct recruitment patterns of these Annexins regulate the subsequent recruitment of RhoGEF2 and RhoGEF3 through actin stabilization to form a robust actomyosin ring. Surprisingly, while the wound does not close in the absence of calcium influx, we find that reduced calcium influx can still initiate repair processes, albeit leading to severe repair phenotypes. Thus, our results suggest that, in addition to initiating repair events, the quantity of calcium influx is important for precise Annexin spatiotemporal protein recruitment to cell wounds and efficient wound repair.
{"title":"Calcium influx rapidly establishes distinct spatial recruitments of Annexins to cell wounds.","authors":"Mitsutoshi Nakamura, Susan M Parkhurst","doi":"10.1093/genetics/iyae101","DOIUrl":"10.1093/genetics/iyae101","url":null,"abstract":"<p><p>To survive daily damage, the formation of actomyosin ring at the wound edge is required to rapidly close cell wounds. Calcium influx is one of the start signals for these cell wound repair events. Here, we find that the rapid recruitment of all 3 Drosophila calcium-responding and phospholipid-binding Annexin proteins (AnxB9, AnxB10, and AnxB11) to distinct regions around the wound is regulated by the quantity of calcium influx rather than their binding to specific phospholipids. The distinct recruitment patterns of these Annexins regulate the subsequent recruitment of RhoGEF2 and RhoGEF3 through actin stabilization to form a robust actomyosin ring. Surprisingly, while the wound does not close in the absence of calcium influx, we find that reduced calcium influx can still initiate repair processes, albeit leading to severe repair phenotypes. Thus, our results suggest that, in addition to initiating repair events, the quantity of calcium influx is important for precise Annexin spatiotemporal protein recruitment to cell wounds and efficient wound repair.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318688","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}
Pub Date : 2024-08-07DOI: 10.1093/genetics/iyae072
Meera V Sundaram, Nathalie Pujol
Apical extracellular matrices (aECMs) coat the exposed surfaces of animal bodies to shape tissues, influence social interactions, and protect against pathogens and other environmental challenges. In the nematode Caenorhabditis elegans, collagenous cuticle and zona pellucida protein-rich precuticle aECMs alternately coat external epithelia across the molt cycle and play many important roles in the worm's development, behavior, and physiology. Both these types of aECMs contain many matrix proteins related to those in vertebrates, as well as some that are nematode-specific. Extensive differences observed among tissues and life stages demonstrate that aECMs are a major feature of epithelial cell identity. In addition to forming discrete layers, some cuticle components assemble into complex substructures such as ridges, furrows, and nanoscale pillars. The epidermis and cuticle are mechanically linked, allowing the epidermis to sense cuticle damage and induce protective innate immune and stress responses. The C. elegans model, with its optical transparency, facilitates the study of aECM cell biology and structure/function relationships and all the myriad ways by which aECM can influence an organism.
{"title":"The Caenorhabditis elegans cuticle and precuticle: a model for studying dynamic apical extracellular matrices in vivo.","authors":"Meera V Sundaram, Nathalie Pujol","doi":"10.1093/genetics/iyae072","DOIUrl":"10.1093/genetics/iyae072","url":null,"abstract":"<p><p>Apical extracellular matrices (aECMs) coat the exposed surfaces of animal bodies to shape tissues, influence social interactions, and protect against pathogens and other environmental challenges. In the nematode Caenorhabditis elegans, collagenous cuticle and zona pellucida protein-rich precuticle aECMs alternately coat external epithelia across the molt cycle and play many important roles in the worm's development, behavior, and physiology. Both these types of aECMs contain many matrix proteins related to those in vertebrates, as well as some that are nematode-specific. Extensive differences observed among tissues and life stages demonstrate that aECMs are a major feature of epithelial cell identity. In addition to forming discrete layers, some cuticle components assemble into complex substructures such as ridges, furrows, and nanoscale pillars. The epidermis and cuticle are mechanically linked, allowing the epidermis to sense cuticle damage and induce protective innate immune and stress responses. The C. elegans model, with its optical transparency, facilitates the study of aECM cell biology and structure/function relationships and all the myriad ways by which aECM can influence an organism.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601988","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}
Pub Date : 2024-08-07DOI: 10.1093/genetics/iyae092
Grant W Brown
APOBEC proteins are cytidine deaminases that restrict the replication of viruses and transposable elements. Several members of the APOBEC3 family, APOBEC3A, APOBEC3B, and APOBEC3H-I, can access the nucleus and cause what is thought to be indiscriminate deamination of the genome, resulting in mutagenesis and genome instability. Although APOBEC3C is also present in the nucleus, the full scope of its deamination target preferences is unknown. By expressing human APOBEC3C in a yeast model system, I have defined the APOBEC3C mutation signature, as well as the preferred genome features of APOBEC3C targets. The APOBEC3C mutation signature is distinct from those of the known cancer genome mutators APOBEC3A and APOBEC3B. APOBEC3C produces DNA strand-coordinated mutation clusters, and APOBEC3C mutations are enriched near the transcription start sites of active genes. Surprisingly, APOBEC3C lacks the bias for the lagging strand of DNA replication that is seen for APOBEC3A and APOBEC3B. The unique preferences of APOBEC3C constitute a mutation profile that will be useful in defining sites of APOBEC3C mutagenesis in human genomes.
{"title":"The cytidine deaminase APOBEC3C has unique sequence and genome feature preferences.","authors":"Grant W Brown","doi":"10.1093/genetics/iyae092","DOIUrl":"10.1093/genetics/iyae092","url":null,"abstract":"<p><p>APOBEC proteins are cytidine deaminases that restrict the replication of viruses and transposable elements. Several members of the APOBEC3 family, APOBEC3A, APOBEC3B, and APOBEC3H-I, can access the nucleus and cause what is thought to be indiscriminate deamination of the genome, resulting in mutagenesis and genome instability. Although APOBEC3C is also present in the nucleus, the full scope of its deamination target preferences is unknown. By expressing human APOBEC3C in a yeast model system, I have defined the APOBEC3C mutation signature, as well as the preferred genome features of APOBEC3C targets. The APOBEC3C mutation signature is distinct from those of the known cancer genome mutators APOBEC3A and APOBEC3B. APOBEC3C produces DNA strand-coordinated mutation clusters, and APOBEC3C mutations are enriched near the transcription start sites of active genes. Surprisingly, APOBEC3C lacks the bias for the lagging strand of DNA replication that is seen for APOBEC3A and APOBEC3B. The unique preferences of APOBEC3C constitute a mutation profile that will be useful in defining sites of APOBEC3C mutagenesis in human genomes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471824","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 : 2024-08-07DOI: 10.1093/genetics/iyae095
Shizhong Xu
The main objective of mapping quantitative trait loci (QTL) and genome-wide association studies (GWAS) is to identify and locate QTLs on the genome. Estimating the sizes of QTL is equally important as identifying the QTLs. The size of a QTL is often measured by the QTL variance, or the proportion of phenotypic variance explained by the QTL, known as the QTL heritability. The reported QTL heritability is biased upward for small-sized QTLs estimated from small samples, especially in GWAS with a very small P-value threshold accommodating to Bonferroni correction for multiple tests. The phenomenon is called the Beavis effect. Methods of correcting the Beavis effect have been developed for additive effect models. Corresponding methods are not available for QTLs with more than one effect, such as QTLs including dominance and other genetic effects. In this study, we developed explicit formulas for estimating the variances and heritability for QTL with multiple effects. We also developed a method to remove nuisance parameters via an annihilator matrix. Finally, biases in estimated QTL variances caused by the Beavis effect are investigated and corrected. The new method is demonstrated by analyzing the 1000 grain weight (KGW) trait in a hybrid rice population.
{"title":"Estimating genetic variance contributed by a quantitative trait locus: removing nuisance parameters.","authors":"Shizhong Xu","doi":"10.1093/genetics/iyae095","DOIUrl":"10.1093/genetics/iyae095","url":null,"abstract":"<p><p>The main objective of mapping quantitative trait loci (QTL) and genome-wide association studies (GWAS) is to identify and locate QTLs on the genome. Estimating the sizes of QTL is equally important as identifying the QTLs. The size of a QTL is often measured by the QTL variance, or the proportion of phenotypic variance explained by the QTL, known as the QTL heritability. The reported QTL heritability is biased upward for small-sized QTLs estimated from small samples, especially in GWAS with a very small P-value threshold accommodating to Bonferroni correction for multiple tests. The phenomenon is called the Beavis effect. Methods of correcting the Beavis effect have been developed for additive effect models. Corresponding methods are not available for QTLs with more than one effect, such as QTLs including dominance and other genetic effects. In this study, we developed explicit formulas for estimating the variances and heritability for QTL with multiple effects. We also developed a method to remove nuisance parameters via an annihilator matrix. Finally, biases in estimated QTL variances caused by the Beavis effect are investigated and corrected. The new method is demonstrated by analyzing the 1000 grain weight (KGW) trait in a hybrid rice population.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307235","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 : 2024-08-07DOI: 10.1093/genetics/iyae128
Gurvir Singh, Robert V Skibbens
Cohesins promote proper chromosome segregation, gene transcription, genomic architecture, DNA condensation, and DNA damage repair. Mutations in either cohesin subunits or regulatory genes can give rise to severe developmental abnormalities (such as Robert Syndrome and Cornelia de Lange Syndrome) and also are highly correlated with cancer. Despite this, little is known about cohesin regulation. Eco1 (ESCO2/EFO2 in humans) and Rad61 (WAPL in humans) represent two such regulators but perform opposing roles. Eco1 acetylation of cohesin during S phase, for instance, stabilizes cohesin-DNA binding to promote sister chromatid cohesion. On the other hand, Rad61 promotes the dissociation of cohesin from DNA. While Eco1 is essential, ECO1 and RAD61 co-deletion results in yeast cell viability, but only within a limited temperature range. Here, we report that eco1 rad61 cell lethality is due to reduced levels of the cohesin subunit Mcd1. Results from a suppressor screen further reveals that FDO1 deletion rescues the temperature sensitive (ts) growth defects exhibited by eco1 rad61 double mutant cells by increasing Mcd1 levels. Regulation of MCD1 expression, however, appears more complex. Elevated expression of MBP1, which encodes a subunit of the MBF transcription complex, also rescues eco1 rad61 cell growth defects. Elevated expression of SWI6, however, which encodes the Mbp1-binding partner of MBF, exacerbates eco1 rad61 cell growth and also abrogates the Mpb1-dependent rescue. Finally, we identify two additional transcription factors, Fkh1 and Fkh2, that impact MCD1 expression. In combination, these findings provide new insights into the nuanced and multi-faceted transcriptional pathways that impact MCD1 expression.
{"title":"Fdo1, Fkh1, Fkh2 and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae.","authors":"Gurvir Singh, Robert V Skibbens","doi":"10.1093/genetics/iyae128","DOIUrl":"https://doi.org/10.1093/genetics/iyae128","url":null,"abstract":"<p><p>Cohesins promote proper chromosome segregation, gene transcription, genomic architecture, DNA condensation, and DNA damage repair. Mutations in either cohesin subunits or regulatory genes can give rise to severe developmental abnormalities (such as Robert Syndrome and Cornelia de Lange Syndrome) and also are highly correlated with cancer. Despite this, little is known about cohesin regulation. Eco1 (ESCO2/EFO2 in humans) and Rad61 (WAPL in humans) represent two such regulators but perform opposing roles. Eco1 acetylation of cohesin during S phase, for instance, stabilizes cohesin-DNA binding to promote sister chromatid cohesion. On the other hand, Rad61 promotes the dissociation of cohesin from DNA. While Eco1 is essential, ECO1 and RAD61 co-deletion results in yeast cell viability, but only within a limited temperature range. Here, we report that eco1 rad61 cell lethality is due to reduced levels of the cohesin subunit Mcd1. Results from a suppressor screen further reveals that FDO1 deletion rescues the temperature sensitive (ts) growth defects exhibited by eco1 rad61 double mutant cells by increasing Mcd1 levels. Regulation of MCD1 expression, however, appears more complex. Elevated expression of MBP1, which encodes a subunit of the MBF transcription complex, also rescues eco1 rad61 cell growth defects. Elevated expression of SWI6, however, which encodes the Mbp1-binding partner of MBF, exacerbates eco1 rad61 cell growth and also abrogates the Mpb1-dependent rescue. Finally, we identify two additional transcription factors, Fkh1 and Fkh2, that impact MCD1 expression. In combination, these findings provide new insights into the nuanced and multi-faceted transcriptional pathways that impact MCD1 expression.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903321","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 : 2024-08-07DOI: 10.1093/genetics/iyae088
Juan Wang, Maureen M Barr, Ann M Wehman
Extracellular vesicles (EVs) encompass a diverse array of membrane-bound organelles released outside cells in response to developmental and physiological cell needs. EVs play important roles in remodeling the shape and content of differentiating cells and can rescue damaged cells from toxic or dysfunctional content. EVs can send signals and transfer metabolites between tissues and organisms to regulate development, respond to stress or tissue damage, or alter mating behaviors. While many EV functions have been uncovered by characterizing ex vivo EVs isolated from body fluids and cultured cells, research using the nematode Caenorhabditis elegans has provided insights into the in vivo functions, biogenesis, and uptake pathways. The C. elegans EV field has also developed methods to analyze endogenous EVs within the organismal context of development and adult physiology in free-living, behaving animals. In this review, we summarize major themes that have emerged for C. elegans EVs and their relevance to human health and disease. We also highlight the diversity of biogenesis mechanisms, locations, and functions of worm EVs and discuss open questions and unexplored topics tenable in C. elegans, given the nematode model is ideal for light and electron microscopy, genetic screens, genome engineering, and high-throughput omics.
细胞外囊泡(EVs)包括各种膜结合细胞器,它们根据细胞的发育和生理需求被释放到细胞外。EVs在重塑分化细胞的形状和内容物方面发挥着重要作用,并能从有毒或功能失调的内容物中拯救受损细胞。EV可在组织和生物体之间传递信号和代谢物,以调节发育、应对压力或组织损伤,或改变交配行为。通过对从体液和培养细胞中分离出来的体内外 EV 进行表征,我们发现了许多 EV 的功能,而利用秀丽隐杆线虫(Caenorhabditis elegans)进行的研究则让我们对体内 EV 的功能、生物生成和吸收途径有了更深入的了解。线虫 EV 领域还开发出了在自由生活、有行为的动物的发育和成体生理学的有机体背景下分析内源性 EV 的方法。在这篇综述中,我们总结了线虫 EVs 出现的主要主题及其与人类健康和疾病的相关性。我们还强调了蠕虫 EVs 的生物发生机制、位置和功能的多样性,并讨论了线虫的开放性问题和尚未探索的课题,因为线虫模型是光镜和电子显微镜、基因筛选、基因组工程和高通量组学的理想选择。
{"title":"Extracellular vesicles.","authors":"Juan Wang, Maureen M Barr, Ann M Wehman","doi":"10.1093/genetics/iyae088","DOIUrl":"10.1093/genetics/iyae088","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) encompass a diverse array of membrane-bound organelles released outside cells in response to developmental and physiological cell needs. EVs play important roles in remodeling the shape and content of differentiating cells and can rescue damaged cells from toxic or dysfunctional content. EVs can send signals and transfer metabolites between tissues and organisms to regulate development, respond to stress or tissue damage, or alter mating behaviors. While many EV functions have been uncovered by characterizing ex vivo EVs isolated from body fluids and cultured cells, research using the nematode Caenorhabditis elegans has provided insights into the in vivo functions, biogenesis, and uptake pathways. The C. elegans EV field has also developed methods to analyze endogenous EVs within the organismal context of development and adult physiology in free-living, behaving animals. In this review, we summarize major themes that have emerged for C. elegans EVs and their relevance to human health and disease. We also highlight the diversity of biogenesis mechanisms, locations, and functions of worm EVs and discuss open questions and unexplored topics tenable in C. elegans, given the nematode model is ideal for light and electron microscopy, genetic screens, genome engineering, and high-throughput omics.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332329","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}
Pub Date : 2024-08-07DOI: 10.1093/genetics/iyae087
Kalpana Makhijani, Jordan Mar, Ivana Gaziova, Krishna Moorthi Bhat
The T-box (Tbx) proteins have a 180-230 amino acid DNA-binding domain, first reported in the Brachyury (T) protein. They are highly conserved among metazoans. They regulate a multitude of cellular functions in development and disease. Here, we report posttranscriptional and translational regulation of midline (mid), a Tbx member in Drosophila. We found that the 3'UTR of mid has mRNA degradation elements and AT-rich sequences. In Schneider S2 cells, mid-mRNA could be detected only when the transgene was without the 3'UTR. Similarly, the 3'UTR linked to the Renilla luciferase reporter significantly reduced the activity of the Luciferase, whereas deleting only the degradation elements from the 3'UTR resulted in reduced activity, but not as much. Overexpression of mid in MP2, an embryonic neuroblast, showed no significant difference in the levels of mid-mRNA between the 2 transgenes, with and without the 3'UTR, indicating the absence of posttranscriptional regulation of mid in MP2. Moreover, while elevated mid-RNA was detected in MP2 in nearly all hemisegments, only a fifth of those hemisegments had elevated levels of the protein. Overexpression of the 2 transgenes resulted in MP2-lineage defects at about the same frequency. These results indicate a translational/posttranslational regulation of mid in MP2. The regulation of ectopically expressed mid in the wing imaginal disc was complex. In the wing disc, where mid is not expressed, the ectopic expression of the transgene lacking the 3'UTR had a higher level of mid-RNA and the protein had a stronger phenotypic effect. These results indicate that the 3'UTR can subject mid-mRNA to degradation in a cell- and tissue-specific manner. We further report a balancer-mediated transgenerational modifier effect on the expression and gain of function effects of the 2 transgenes.
{"title":"Posttranscriptional regulation of the T-box gene midline via the 3'UTR in Drosophila is complex and cell- and tissue-dependent.","authors":"Kalpana Makhijani, Jordan Mar, Ivana Gaziova, Krishna Moorthi Bhat","doi":"10.1093/genetics/iyae087","DOIUrl":"10.1093/genetics/iyae087","url":null,"abstract":"<p><p>The T-box (Tbx) proteins have a 180-230 amino acid DNA-binding domain, first reported in the Brachyury (T) protein. They are highly conserved among metazoans. They regulate a multitude of cellular functions in development and disease. Here, we report posttranscriptional and translational regulation of midline (mid), a Tbx member in Drosophila. We found that the 3'UTR of mid has mRNA degradation elements and AT-rich sequences. In Schneider S2 cells, mid-mRNA could be detected only when the transgene was without the 3'UTR. Similarly, the 3'UTR linked to the Renilla luciferase reporter significantly reduced the activity of the Luciferase, whereas deleting only the degradation elements from the 3'UTR resulted in reduced activity, but not as much. Overexpression of mid in MP2, an embryonic neuroblast, showed no significant difference in the levels of mid-mRNA between the 2 transgenes, with and without the 3'UTR, indicating the absence of posttranscriptional regulation of mid in MP2. Moreover, while elevated mid-RNA was detected in MP2 in nearly all hemisegments, only a fifth of those hemisegments had elevated levels of the protein. Overexpression of the 2 transgenes resulted in MP2-lineage defects at about the same frequency. These results indicate a translational/posttranslational regulation of mid in MP2. The regulation of ectopically expressed mid in the wing imaginal disc was complex. In the wing disc, where mid is not expressed, the ectopic expression of the transgene lacking the 3'UTR had a higher level of mid-RNA and the protein had a stronger phenotypic effect. These results indicate that the 3'UTR can subject mid-mRNA to degradation in a cell- and tissue-specific manner. We further report a balancer-mediated transgenerational modifier effect on the expression and gain of function effects of the 2 transgenes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156763","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 : 2024-08-07DOI: 10.1093/genetics/iyae091
Yifan Chen, Agata Burian, Frank Johannes
Plant architecture is shaped by the production of new organs, most of which emerge postembryonically. This process includes the formation of new lateral branches along existing shoots. Current evidence supports a detached-meristem model as the cellular basis of lateral shoot initiation. In this model, a small number of undifferentiated cells are sampled from the periphery of the shoot apical meristem (SAM) to act as precursors for axillary buds, which eventually develop into new shoots. Repeated branching thus creates cellular bottlenecks (i.e. somatic drift) that affect how de novo (epi)genetic mutations propagate through the plant body during development. Somatic drift could be particularly relevant for stochastic DNA methylation gains and losses (i.e. spontaneous epimutations), as they have been shown to arise rapidly with each cell division. Here, we formalize a special case of the detached-meristem model, where precursor cells are randomly sampled from the SAM periphery in a way that maximizes cell lineage independence. We show that somatic drift during repeated branching gives rise to a mixture of cellular phylogenies within the SAM over time. This process is dependent on the number of branch points, the strength of drift as well as the epimutation rate. Our model predicts that cell-to-cell DNA methylation heterogeneity in the SAM converges to nonzero states during development, suggesting that epigenetic variation is an inherent property of the SAM cell population. Our insights have direct implications for empirical studies of somatic (epi)genomic diversity in long-lived perennial and clonal species using bulk or single-cell sequencing approaches.
植物的结构是由新器官的产生形成的,其中大部分是在胚后出现的。这一过程包括沿着现有嫩枝形成新的侧枝。目前的证据支持将分离的分生组织模型作为侧枝萌发的细胞基础。在这一模型中,少量未分化细胞从嫩枝顶端分生组织(SAM)外围取样,作为腋芽的前体,最终发育成新枝。因此,重复分枝会造成细胞瓶颈(即体细胞漂移),影响新(外)基因突变在植物体发育过程中的传播方式。体细胞漂移与随机 DNA 甲基化增减(即自发表突变)尤其相关,因为它们在每次细胞分裂时都会迅速出现。在这里,我们将分离式分生组织模型的一个特例形式化,在这个特例中,前体细胞是以最大化细胞系独立性的方式从分离式分生组织外围随机取样的。我们的研究表明,重复分枝过程中的体细胞漂移会随着时间的推移在SAM内产生混合的细胞系统发生。这一过程取决于分支点的数量、漂移的强度以及外突变率。我们的模型预测,在发育过程中,SAM 中细胞与细胞之间的 DNA 甲基化异质性会趋近于非零状态,这表明表观遗传变异是 SAM 细胞群的固有属性。我们的见解对使用大量或单细胞测序方法对长寿多年生和克隆物种的体细胞(表)基因组多样性进行实证研究有直接影响。
{"title":"Somatic epigenetic drift during shoot branching: a cell lineage-based model.","authors":"Yifan Chen, Agata Burian, Frank Johannes","doi":"10.1093/genetics/iyae091","DOIUrl":"10.1093/genetics/iyae091","url":null,"abstract":"<p><p>Plant architecture is shaped by the production of new organs, most of which emerge postembryonically. This process includes the formation of new lateral branches along existing shoots. Current evidence supports a detached-meristem model as the cellular basis of lateral shoot initiation. In this model, a small number of undifferentiated cells are sampled from the periphery of the shoot apical meristem (SAM) to act as precursors for axillary buds, which eventually develop into new shoots. Repeated branching thus creates cellular bottlenecks (i.e. somatic drift) that affect how de novo (epi)genetic mutations propagate through the plant body during development. Somatic drift could be particularly relevant for stochastic DNA methylation gains and losses (i.e. spontaneous epimutations), as they have been shown to arise rapidly with each cell division. Here, we formalize a special case of the detached-meristem model, where precursor cells are randomly sampled from the SAM periphery in a way that maximizes cell lineage independence. We show that somatic drift during repeated branching gives rise to a mixture of cellular phylogenies within the SAM over time. This process is dependent on the number of branch points, the strength of drift as well as the epimutation rate. Our model predicts that cell-to-cell DNA methylation heterogeneity in the SAM converges to nonzero states during development, suggesting that epigenetic variation is an inherent property of the SAM cell population. Our insights have direct implications for empirical studies of somatic (epi)genomic diversity in long-lived perennial and clonal species using bulk or single-cell sequencing approaches.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162795","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 : 2024-08-07DOI: 10.1093/genetics/iyae089
Megan L Smith, Matthew W Hahn
Detecting introgression between closely related populations or species is a fundamental objective in evolutionary biology. Existing methods for detecting migration and inferring migration rates from population genetic data often assume a neutral model of evolution. Growing evidence of the pervasive impact of selection on large portions of the genome across diverse taxa suggests that this assumption is unrealistic in most empirical systems. Further, ignoring selection has previously been shown to negatively impact demographic inferences (e.g. of population size histories). However, the impacts of biologically realistic selection on inferences of migration remain poorly explored. Here, we simulate data under models of background selection, selective sweeps, balancing selection, and adaptive introgression. We show that ignoring selection sometimes leads to false inferences of migration in popularly used methods that rely on the site frequency spectrum. Specifically, balancing selection and some models of background selection result in the rejection of isolation-only models in favor of isolation-with-migration models and lead to elevated estimates of migration rates. BPP, a method that analyzes sequence data directly, showed false positives for all conditions at recent divergence times, but balancing selection also led to false positives at medium-divergence times. Our results suggest that such methods may be unreliable in some empirical systems, such that new methods that are robust to selection need to be developed.
{"title":"Selection leads to false inferences of introgression using popular methods.","authors":"Megan L Smith, Matthew W Hahn","doi":"10.1093/genetics/iyae089","DOIUrl":"10.1093/genetics/iyae089","url":null,"abstract":"<p><p>Detecting introgression between closely related populations or species is a fundamental objective in evolutionary biology. Existing methods for detecting migration and inferring migration rates from population genetic data often assume a neutral model of evolution. Growing evidence of the pervasive impact of selection on large portions of the genome across diverse taxa suggests that this assumption is unrealistic in most empirical systems. Further, ignoring selection has previously been shown to negatively impact demographic inferences (e.g. of population size histories). However, the impacts of biologically realistic selection on inferences of migration remain poorly explored. Here, we simulate data under models of background selection, selective sweeps, balancing selection, and adaptive introgression. We show that ignoring selection sometimes leads to false inferences of migration in popularly used methods that rely on the site frequency spectrum. Specifically, balancing selection and some models of background selection result in the rejection of isolation-only models in favor of isolation-with-migration models and lead to elevated estimates of migration rates. BPP, a method that analyzes sequence data directly, showed false positives for all conditions at recent divergence times, but balancing selection also led to false positives at medium-divergence times. Our results suggest that such methods may be unreliable in some empirical systems, such that new methods that are robust to selection need to be developed.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156796","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}