Pub Date : 2024-08-07DOI: 10.1186/s12915-024-01962-6
Wen-Hsi Kuo, Sara J Wright, Linda L Small, Kenneth M Olsen
Background: White clover (Trifolium repens) is a globally important perennial forage legume. This species also serves as an eco-evolutionary model system for studying within-species chemical defense variation; it features a well-studied polymorphism for cyanogenesis (HCN release following tissue damage), with higher frequencies of cyanogenic plants favored in warmer locations worldwide. Using a newly generated haplotype-resolved genome and two other long-read assemblies, we tested the hypothesis that copy number variants (CNVs) at cyanogenesis genes play a role in the ability of white clover to rapidly adapt to local environments. We also examined questions on subgenome evolution in this recently evolved allotetraploid species and on chromosomal rearrangements in the broader IRLC legume clade.
Results: Integration of PacBio HiFi, Omni-C, Illumina, and linkage map data yielded a completely de novo genome assembly for white clover (created without a priori sequence assignment to subgenomes). We find that white clover has undergone extensive transposon diversification since its origin but otherwise shows highly conserved genome organization and composition with its diploid progenitors. Unlike some other clover species, its chromosomal structure is conserved with other IRLC legumes. We further find extensive evidence of CNVs at the major cyanogenesis loci; these contribute to quantitative variation in the cyanogenic phenotype and to local adaptation across wild North American populations.
Conclusions: This work provides a case study documenting the role of CNVs in local adaptation in a plant species, and it highlights the value of pan-genome data for identifying contributions of structural variants to adaptation in nature.
{"title":"De novo genome assembly of white clover (Trifolium repens L.) reveals the role of copy number variation in rapid environmental adaptation.","authors":"Wen-Hsi Kuo, Sara J Wright, Linda L Small, Kenneth M Olsen","doi":"10.1186/s12915-024-01962-6","DOIUrl":"10.1186/s12915-024-01962-6","url":null,"abstract":"<p><strong>Background: </strong>White clover (Trifolium repens) is a globally important perennial forage legume. This species also serves as an eco-evolutionary model system for studying within-species chemical defense variation; it features a well-studied polymorphism for cyanogenesis (HCN release following tissue damage), with higher frequencies of cyanogenic plants favored in warmer locations worldwide. Using a newly generated haplotype-resolved genome and two other long-read assemblies, we tested the hypothesis that copy number variants (CNVs) at cyanogenesis genes play a role in the ability of white clover to rapidly adapt to local environments. We also examined questions on subgenome evolution in this recently evolved allotetraploid species and on chromosomal rearrangements in the broader IRLC legume clade.</p><p><strong>Results: </strong>Integration of PacBio HiFi, Omni-C, Illumina, and linkage map data yielded a completely de novo genome assembly for white clover (created without a priori sequence assignment to subgenomes). We find that white clover has undergone extensive transposon diversification since its origin but otherwise shows highly conserved genome organization and composition with its diploid progenitors. Unlike some other clover species, its chromosomal structure is conserved with other IRLC legumes. We further find extensive evidence of CNVs at the major cyanogenesis loci; these contribute to quantitative variation in the cyanogenic phenotype and to local adaptation across wild North American populations.</p><p><strong>Conclusions: </strong>This work provides a case study documenting the role of CNVs in local adaptation in a plant species, and it highlights the value of pan-genome data for identifying contributions of structural variants to adaptation in nature.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 10.1186/s12915-024-01963-5
Qinhuan Luo, Yaozhu Chen, Xun Lan
Background: Single-cell RNA sequencing enables studying cells individually, yet high gene dimensions and low cell numbers challenge analysis. And only a subset of the genes detected are involved in the biological processes underlying cell-type specific functions.
Result: In this study, we present COMSE, an unsupervised feature selection framework using community detection to capture informative genes from scRNA-seq data. COMSE identified homogenous cell substates with high resolution, as demonstrated by distinguishing different cell cycle stages. Evaluations based on real and simulated scRNA-seq datasets showed COMSE outperformed methods even with high dropout rates in cell clustering assignment. We also demonstrate that by identifying communities of genes associated with batch effects, COMSE parses signals reflecting biological difference from noise arising due to differences in sequencing protocols, thereby enabling integrated analysis of scRNA-seq datasets of different sources.
Conclusions: COMSE provides an efficient unsupervised framework that selects highly informative genes in scRNA-seq data improving cell sub-states identification and cell clustering. It identifies gene subsets that reveal biological and technical heterogeneity, supporting applications like batch effect correction and pathway analysis. It also provides robust results for bulk RNA-seq data analysis.
{"title":"COMSE: analysis of single-cell RNA-seq data using community detection-based feature selection.","authors":"Qinhuan Luo, Yaozhu Chen, Xun Lan","doi":"10.1186/s12915-024-01963-5","DOIUrl":"10.1186/s12915-024-01963-5","url":null,"abstract":"<p><strong>Background: </strong>Single-cell RNA sequencing enables studying cells individually, yet high gene dimensions and low cell numbers challenge analysis. And only a subset of the genes detected are involved in the biological processes underlying cell-type specific functions.</p><p><strong>Result: </strong>In this study, we present COMSE, an unsupervised feature selection framework using community detection to capture informative genes from scRNA-seq data. COMSE identified homogenous cell substates with high resolution, as demonstrated by distinguishing different cell cycle stages. Evaluations based on real and simulated scRNA-seq datasets showed COMSE outperformed methods even with high dropout rates in cell clustering assignment. We also demonstrate that by identifying communities of genes associated with batch effects, COMSE parses signals reflecting biological difference from noise arising due to differences in sequencing protocols, thereby enabling integrated analysis of scRNA-seq datasets of different sources.</p><p><strong>Conclusions: </strong>COMSE provides an efficient unsupervised framework that selects highly informative genes in scRNA-seq data improving cell sub-states identification and cell clustering. It identifies gene subsets that reveal biological and technical heterogeneity, supporting applications like batch effect correction and pathway analysis. It also provides robust results for bulk RNA-seq data analysis.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.
Results: Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.
Conclusions: These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.
{"title":"Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut.","authors":"Hiroki Nagai, Yuya Adachi, Tenki Nakasugi, Ema Takigawa, Junichiro Ui, Takashi Makino, Masayuki Miura, Yu-Ichiro Nakajima","doi":"10.1186/s12915-024-01956-4","DOIUrl":"10.1186/s12915-024-01956-4","url":null,"abstract":"<p><strong>Background: </strong>The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.</p><p><strong>Results: </strong>Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.</p><p><strong>Conclusions: </strong>These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01960-8
R R Senji Laxme, Suyog Khochare, Siddharth Bhatia, Gerard Martin, Kartik Sunagar
Background: Snake venoms can exhibit remarkable inter- and intraspecific variation. While diverse ecological and environmental factors are theorised to explain this variation, only a handful of studies have attempted to unravel their precise roles. This knowledge gap not only impedes our understanding of venom evolution but may also have dire consequences on snakebite treatment. To address this shortcoming, we investigated the evolutionary ecology of venoms of Russell's viper (Daboia russelii) and spectacled cobra (Naja naja), India's two clinically most important snakes responsible for an alarming number of human deaths and disabilities.
Methodology: Several individuals (n = 226) of D. russelii and N. naja belonging to multiple clutches (n = 9) and their mothers were maintained in captivity to source ontogenetic stage-specific venoms. Using various in vitro and in vivo assays, we assessed the significance of prey, ontogeny and sex in driving venom composition, function, and potency.
Results: Considerable ontogenetic shifts in venom profiles were observed in D. russelii, with the venoms of newborns being many times as potent as juveniles and adults against mammalian (2.3-2.5 ×) and reptilian (2-10 ×) prey. This is the first documentation of the ontogenetic shift in viperine snakes. In stark contrast, N. naja, which shares a biogeographic distribution similar to D. russelii, deployed identical biochemical cocktails across development. Furthermore, the binding kinetics of cobra venom toxins against synthetic target receptors from various prey and predators shed light on the evolutionary arms race.
Conclusions: Our findings, therefore, provide fascinating insights into the roles of ecology and life history traits in shaping snake venoms.
背景:蛇毒可在种间和种内表现出显著的差异。虽然理论上有多种生态和环境因素可以解释这种变化,但只有少数研究试图揭示这些因素的确切作用。这一知识空白不仅阻碍了我们对毒液进化的理解,还可能对蛇咬伤的治疗造成严重后果。为了弥补这一不足,我们研究了罗素蝰(Daboia russelii)和眼镜蛇(Naja naja)毒液的进化生态学:方法:人工饲养了属于多窝(n = 9)的眼镜蛇(D. russelii)和眼镜蛇(N. naja)的若干个体(n = 226)及其母蛇,以获取其本体发育阶段的特异性毒液。通过各种体外和体内试验,我们评估了猎物、个体发育和性别对毒液成分、功能和效力的影响:结果:我们观察到D. russelii的毒液特征在发育过程中发生了显著变化,新生儿的毒液对哺乳动物(2.3-2.5倍)和爬行动物(2-10倍)猎物的毒性是幼体和成体的数倍。这是首次记录蝰蛇的个体发育转变。与此形成鲜明对比的是,与 D. russelii 的生物地理分布相似的 N. naja 在整个发育过程中部署了相同的生化组合。此外,眼镜蛇毒液毒素与来自不同猎物和捕食者的合成靶受体的结合动力学也揭示了进化军备竞赛:因此,我们的发现为生态学和生活史特征在蛇毒形成过程中的作用提供了令人着迷的见解。
{"title":"From birth to bite: the evolutionary ecology of India's medically most important snake venoms.","authors":"R R Senji Laxme, Suyog Khochare, Siddharth Bhatia, Gerard Martin, Kartik Sunagar","doi":"10.1186/s12915-024-01960-8","DOIUrl":"10.1186/s12915-024-01960-8","url":null,"abstract":"<p><strong>Background: </strong>Snake venoms can exhibit remarkable inter- and intraspecific variation. While diverse ecological and environmental factors are theorised to explain this variation, only a handful of studies have attempted to unravel their precise roles. This knowledge gap not only impedes our understanding of venom evolution but may also have dire consequences on snakebite treatment. To address this shortcoming, we investigated the evolutionary ecology of venoms of Russell's viper (Daboia russelii) and spectacled cobra (Naja naja), India's two clinically most important snakes responsible for an alarming number of human deaths and disabilities.</p><p><strong>Methodology: </strong>Several individuals (n = 226) of D. russelii and N. naja belonging to multiple clutches (n = 9) and their mothers were maintained in captivity to source ontogenetic stage-specific venoms. Using various in vitro and in vivo assays, we assessed the significance of prey, ontogeny and sex in driving venom composition, function, and potency.</p><p><strong>Results: </strong>Considerable ontogenetic shifts in venom profiles were observed in D. russelii, with the venoms of newborns being many times as potent as juveniles and adults against mammalian (2.3-2.5 ×) and reptilian (2-10 ×) prey. This is the first documentation of the ontogenetic shift in viperine snakes. In stark contrast, N. naja, which shares a biogeographic distribution similar to D. russelii, deployed identical biochemical cocktails across development. Furthermore, the binding kinetics of cobra venom toxins against synthetic target receptors from various prey and predators shed light on the evolutionary arms race.</p><p><strong>Conclusions: </strong>Our findings, therefore, provide fascinating insights into the roles of ecology and life history traits in shaping snake venoms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01959-1
Haihua Liu, Zhijian Wang, Yanjun Li, Qian Chen, Sijia Jiang, Yue Gao, Jing Wang, Yali Chi, Jie Liu, Xiaoli Wu, Qiong Chen, Chaoqun Xiao, Mei Zhong, Chunlin Chen, Xinping Yang
Background: Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear.
Results: Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells.
Conclusions: Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.
{"title":"Hierarchical lncRNA regulatory network in early-onset severe preeclampsia.","authors":"Haihua Liu, Zhijian Wang, Yanjun Li, Qian Chen, Sijia Jiang, Yue Gao, Jing Wang, Yali Chi, Jie Liu, Xiaoli Wu, Qiong Chen, Chaoqun Xiao, Mei Zhong, Chunlin Chen, Xinping Yang","doi":"10.1186/s12915-024-01959-1","DOIUrl":"10.1186/s12915-024-01959-1","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear.</p><p><strong>Results: </strong>Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells.</p><p><strong>Conclusions: </strong>Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01952-8
S J Salisbury, R Ruiz Daniels, S J Monaghan, J E Bron, P R Villamayor, O Gervais, M D Fast, L Sveen, R D Houston, N Robinson, D Robledo
Background: Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown.
Results: We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite.
Conclusions: Our results highlight the key role of keratinocytes in coho salmon's sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.
{"title":"Keratinocytes drive the epithelial hyperplasia key to sea lice resistance in coho salmon.","authors":"S J Salisbury, R Ruiz Daniels, S J Monaghan, J E Bron, P R Villamayor, O Gervais, M D Fast, L Sveen, R D Houston, N Robinson, D Robledo","doi":"10.1186/s12915-024-01952-8","DOIUrl":"10.1186/s12915-024-01952-8","url":null,"abstract":"<p><strong>Background: </strong>Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown.</p><p><strong>Results: </strong>We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite.</p><p><strong>Conclusions: </strong>Our results highlight the key role of keratinocytes in coho salmon's sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01958-2
Jing Ding, Ning Xu, Jing Wang, Yushu He, Xuelin Wang, Mingyuan Liu, Xiaolei Liu
Background: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths.
Results: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host.
Conclusions: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.
背景:螺旋旋毛虫(T. spiralis)是一种寄生蠕虫,是一种全球流行的被忽视的人畜共患病,不同发育阶段的蠕虫(肌肉幼虫、成虫、新生幼虫)会在不同感染部位诱发免疫攻击,对宿主健康造成严重危害。一些先天性免疫细胞会释放细胞外捕获器(ETs),捕获并杀死入侵人体的大多数病原体。作为回应,一些单细胞病原体进化出一种策略,通过分泌核酸酶逃避ETs的捕获,但很少有相关研究对多细胞蠕虫进行调查:在本研究中,我们观察到来自中性粒细胞的ETs捕获了螺旋体成虫,而来自巨噬细胞的ETs捕获了肌肉幼虫和新生幼虫,ETs在体外对寄生虫有杀灭作用。为了抵御这种免疫攻击,螺旋体分泌类似 DNase II 的蛋白 Plancitoxin-1 来降解 ETs 并逃脱捕获,这对螺旋体在宿主体内的生存至关重要:总之,这些研究结果表明,螺旋体通过分泌脱氧核糖核酸酶来逃避ET介导的捕获,这是一种潜在的保守免疫逃避机制。
{"title":"Plancitoxin-1 mediates extracellular trap evasion by the parasitic helminth Trichinella spiralis.","authors":"Jing Ding, Ning Xu, Jing Wang, Yushu He, Xuelin Wang, Mingyuan Liu, Xiaolei Liu","doi":"10.1186/s12915-024-01958-2","DOIUrl":"10.1186/s12915-024-01958-2","url":null,"abstract":"<p><strong>Background: </strong>Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths.</p><p><strong>Results: </strong>In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host.</p><p><strong>Conclusions: </strong>In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01955-5
Ernesto Lopes Pinheiro-Junior, Ehsan Alirahimi, Steve Peigneur, Jörg Isensee, Susanne Schiffmann, Pelin Erkoc, Robert Fürst, Andreas Vilcinskas, Tobias Sennoner, Ivan Koludarov, Benjamin-Florian Hempel, Jan Tytgat, Tim Hucho, Björn M von Reumont
Background: The identification of novel toxins from overlooked and taxonomically exceptional species bears potential for various pharmacological applications. The remipede Xibalbanus tulumensis, an underwater cave-dwelling crustacean, is the only crustacean for which a venom system has been described. Its venom contains several xibalbin peptides that have an inhibitor cysteine knot (ICK) scaffold.
Results: Our screenings revealed that all tested xibalbin variants particularly inhibit potassium channels. Xib1 and xib13 with their eight-cysteine domain similar to spider knottins also inhibit voltage-gated sodium channels. No activity was noted on calcium channels. Expanding the functional testing, we demonstrate that xib1 and xib13 increase PKA-II and Erk1/2 sensitization signaling in nociceptive neurons, which may initiate pain sensitization. Our phylogenetic analysis suggests that xib13 either originates from the common ancestor of pancrustaceans or earlier while xib1 is more restricted to remipedes. The ten-cysteine scaffolded xib2 emerged from xib1, a result that is supported by our phylogenetic and machine learning-based analyses.
Conclusions: Our functional characterization of synthesized variants of xib1, xib2, and xib13 elucidates their potential as inhibitors of potassium channels in mammalian systems. The specific interaction of xib2 with Kv1.6 channels, which are relevant to treating variants of epilepsy, shows potential for further studies. At higher concentrations, xib1 and xib13 activate the kinases PKA-II and ERK1/2 in mammalian sensory neurons, suggesting pain sensitization and potential applications related to pain research and therapy. While tested insect channels suggest that all probably act as neurotoxins, the biological function of xib1, xib2, and xib13 requires further elucidation. A novel finding on their evolutionary origin is the apparent emergence of X. tulumensis-specific xib2 from xib1. Our study is an important cornerstone for future studies to untangle the origin and function of these enigmatic proteins as important components of remipede but also other pancrustacean and arthropod venoms.
{"title":"Diversely evolved xibalbin variants from remipede venom inhibit potassium channels and activate PKA-II and Erk1/2 signaling.","authors":"Ernesto Lopes Pinheiro-Junior, Ehsan Alirahimi, Steve Peigneur, Jörg Isensee, Susanne Schiffmann, Pelin Erkoc, Robert Fürst, Andreas Vilcinskas, Tobias Sennoner, Ivan Koludarov, Benjamin-Florian Hempel, Jan Tytgat, Tim Hucho, Björn M von Reumont","doi":"10.1186/s12915-024-01955-5","DOIUrl":"10.1186/s12915-024-01955-5","url":null,"abstract":"<p><strong>Background: </strong>The identification of novel toxins from overlooked and taxonomically exceptional species bears potential for various pharmacological applications. The remipede Xibalbanus tulumensis, an underwater cave-dwelling crustacean, is the only crustacean for which a venom system has been described. Its venom contains several xibalbin peptides that have an inhibitor cysteine knot (ICK) scaffold.</p><p><strong>Results: </strong>Our screenings revealed that all tested xibalbin variants particularly inhibit potassium channels. Xib<sub>1</sub> and xib<sub>13</sub> with their eight-cysteine domain similar to spider knottins also inhibit voltage-gated sodium channels. No activity was noted on calcium channels. Expanding the functional testing, we demonstrate that xib<sub>1</sub> and xib<sub>13</sub> increase PKA-II and Erk1/2 sensitization signaling in nociceptive neurons, which may initiate pain sensitization. Our phylogenetic analysis suggests that xib<sub>13</sub> either originates from the common ancestor of pancrustaceans or earlier while xib<sub>1</sub> is more restricted to remipedes. The ten-cysteine scaffolded xib<sub>2</sub> emerged from xib<sub>1</sub>, a result that is supported by our phylogenetic and machine learning-based analyses.</p><p><strong>Conclusions: </strong>Our functional characterization of synthesized variants of xib<sub>1</sub>, xib<sub>2</sub>, and xib<sub>13</sub> elucidates their potential as inhibitors of potassium channels in mammalian systems. The specific interaction of xib<sub>2</sub> with Kv1.6 channels, which are relevant to treating variants of epilepsy, shows potential for further studies. At higher concentrations, xib<sub>1</sub> and xib<sub>13</sub> activate the kinases PKA-II and ERK1/2 in mammalian sensory neurons, suggesting pain sensitization and potential applications related to pain research and therapy. While tested insect channels suggest that all probably act as neurotoxins, the biological function of xib<sub>1</sub>, xib<sub>2,</sub> and xib<sub>13</sub> requires further elucidation. A novel finding on their evolutionary origin is the apparent emergence of X. tulumensis-specific xib<sub>2</sub> from xib<sub>1</sub>. Our study is an important cornerstone for future studies to untangle the origin and function of these enigmatic proteins as important components of remipede but also other pancrustacean and arthropod venoms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01953-7
Parnika S Kadam, Zijian Yang, Youtao Lu, Hua Zhu, Yasemin Atiyas, Nishal Shah, Stephen Fisher, Erik Nordgren, Junhyong Kim, David Issadore, James Eberwine
Background: Mitochondrial (mt) heteroplasmy can cause adverse biological consequences when deleterious mtDNA mutations accumulate disrupting "normal" mt-driven processes and cellular functions. To investigate the heteroplasmy of such mtDNA changes, we developed a moderate throughput mt isolation procedure to quantify the mt single-nucleotide variant (SNV) landscape in individual mouse neurons and astrocytes. In this study, we amplified mt-genomes from 1645 single mitochondria isolated from mouse single astrocytes and neurons to (1) determine the distribution and proportion of mt-SNVs as well as mutation pattern in specific target regions across the mt-genome, (2) assess differences in mtDNA SNVs between neurons and astrocytes, and (3) study co-segregation of variants in the mouse mtDNA.
Results: (1) The data show that specific sites of the mt-genome are permissive to SNV presentation while others appear to be under stringent purifying selection. Nested hierarchical analysis at the levels of mitochondrion, cell, and mouse reveals distinct patterns of inter- and intra-cellular variation for mt-SNVs at different sites. (2) Further, differences in the SNV incidence were observed between mouse neurons and astrocytes for two mt-SNV 9027:G > A and 9419:C > T showing variation in the mutational propensity between these cell types. Purifying selection was observed in neurons as shown by the Ka/Ks statistic, suggesting that neurons are under stronger evolutionary constraint as compared to astrocytes. (3) Intriguingly, these data show strong linkage between the SNV sites at nucleotide positions 9027 and 9461.
Conclusions: This study suggests that segregation as well as clonal expansion of mt-SNVs is specific to individual genomic loci, which is important foundational data in understanding of heteroplasmy and disease thresholds for mutation of pathogenic variants.
{"title":"Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons.","authors":"Parnika S Kadam, Zijian Yang, Youtao Lu, Hua Zhu, Yasemin Atiyas, Nishal Shah, Stephen Fisher, Erik Nordgren, Junhyong Kim, David Issadore, James Eberwine","doi":"10.1186/s12915-024-01953-7","DOIUrl":"10.1186/s12915-024-01953-7","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial (mt) heteroplasmy can cause adverse biological consequences when deleterious mtDNA mutations accumulate disrupting \"normal\" mt-driven processes and cellular functions. To investigate the heteroplasmy of such mtDNA changes, we developed a moderate throughput mt isolation procedure to quantify the mt single-nucleotide variant (SNV) landscape in individual mouse neurons and astrocytes. In this study, we amplified mt-genomes from 1645 single mitochondria isolated from mouse single astrocytes and neurons to (1) determine the distribution and proportion of mt-SNVs as well as mutation pattern in specific target regions across the mt-genome, (2) assess differences in mtDNA SNVs between neurons and astrocytes, and (3) study co-segregation of variants in the mouse mtDNA.</p><p><strong>Results: </strong>(1) The data show that specific sites of the mt-genome are permissive to SNV presentation while others appear to be under stringent purifying selection. Nested hierarchical analysis at the levels of mitochondrion, cell, and mouse reveals distinct patterns of inter- and intra-cellular variation for mt-SNVs at different sites. (2) Further, differences in the SNV incidence were observed between mouse neurons and astrocytes for two mt-SNV 9027:G > A and 9419:C > T showing variation in the mutational propensity between these cell types. Purifying selection was observed in neurons as shown by the Ka/Ks statistic, suggesting that neurons are under stronger evolutionary constraint as compared to astrocytes. (3) Intriguingly, these data show strong linkage between the SNV sites at nucleotide positions 9027 and 9461.</p><p><strong>Conclusions: </strong>This study suggests that segregation as well as clonal expansion of mt-SNVs is specific to individual genomic loci, which is important foundational data in understanding of heteroplasmy and disease thresholds for mutation of pathogenic variants.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-29DOI: 10.1186/s12915-024-01961-7
Jie Chen, Wenting Zhao, Lei Cao, Rute S T Martins, Adelino V M Canário
Background: Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism.
Results: We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20-30% increase in embryonic primordial germ cells, and sst1.2-/- adults laid 40% more eggs than their wild-type siblings. The sst1.1-/- and sst1.2-/- mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass.
Conclusions: We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.
{"title":"Somatostatin signalling coordinates energy metabolism allocation to reproduction in zebrafish.","authors":"Jie Chen, Wenting Zhao, Lei Cao, Rute S T Martins, Adelino V M Canário","doi":"10.1186/s12915-024-01961-7","DOIUrl":"10.1186/s12915-024-01961-7","url":null,"abstract":"<p><strong>Background: </strong>Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism.</p><p><strong>Results: </strong>We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20-30% increase in embryonic primordial germ cells, and sst1.2<sup>-/-</sup> adults laid 40% more eggs than their wild-type siblings. The sst1.1<sup>-/-</sup> and sst1.2<sup>-/-</sup> mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass.</p><p><strong>Conclusions: </strong>We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}