CRISPR （clustered regularly interspaced short palindromic repeats）-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 ge...CRISPR （clustered regularly interspaced short palindromic repeats）-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 genome editing make it ideal for investigating the function of genes in vivo （Hsu et al., 2014）. Gene duplication is a key driver of evolu- tionary novelty （Taylor and Raes, 2004）. However, duplicated genes with near-identical sequences and functional redun- dancy have posed challenges for genetic analysis （Woollard, 2005）. The functions of duplicated genes can be assessed by simultaneous knockdown using homology-based methods such as RNA interference （RNAi） （Tischler et al., 2006）, Generation of double or triple mutants is an alternative way to assess functional redundancy of duplicated genes, However, generation of such compound mutants by forward or reverse genetic methods is time consuming.展开更多
Since the discovery of the first transposon by Dr.Barbara McClintock,the prevalence and diversity of transposable elements(TEs)have been gradually recognized.As fundamental genetic components,TEs drive organismal evol...Since the discovery of the first transposon by Dr.Barbara McClintock,the prevalence and diversity of transposable elements(TEs)have been gradually recognized.As fundamental genetic components,TEs drive organismal evolution not only by contributing functional sequences(e.g.,regulatory elements or“controllers”as phrased by Dr.McClintock)but also by shuffling genomic sequences.In the latter respect,TE-mediated gene duplications have contributed to the origination of new genes and attracted extensive interest.In response to the development of this field,we herein attempt to provide an overview of TEmediated duplication by focusing on common rules emerging across duplications generated by different TE types.Specifically,despite the huge divergence of transposition machinery across TEs,we identify three common features of various TE-mediated duplication mechanisms,including end bypass,template switching,and recurrent transposition.These three features lead to one common functional outcome,namely,TE-mediated duplicates tend to be subjected to exon shuffling and neofunctionalization.Therefore,the intrinsic properties of the mutational mechanism constrain the evolutionary trajectories of these duplicates.We finally discuss the future of this field including an in-depth characterization of both the duplication mechanisms and functions of TE-mediated duplicates.展开更多
It has been shown that duplicate genes on the X chromosome evolve much faster than duplicate genes on autosomes in Drosophila melanogaster. However, whether this phenomenon is general and can be applied to other speci...It has been shown that duplicate genes on the X chromosome evolve much faster than duplicate genes on autosomes in Drosophila melanogaster. However, whether this phenomenon is general and can be applied to other species is not known. Here we examined this issue in chicken that have heterogametic females （females have ZW sex chromosome）. We compared sequence divergence of duplicate genes on the Z chromosome with those on autosomes. We found that duplications on the Z chromosome indeed evolved faster than those on autosomes and show distinct patterns of molecular evolution from autosomal duplications. Examination of the expression of duplicate genes revealed an enrichment of duplications on the Z chromosome having male-biased expression and an enrichment of duplications on the autosomes having female-biased expression. These results suggest an evolutionary trend of the recruitment of duplicate genes towards reproduction-specific function. The faster evolution of duplications on Z than on the autosomes is most likely contributed by the selective forces driving the fixation of adaptive mutations on Z. Therefore, the common phenomena observed in both flies and chicken suggest that duplicate genes on sex chromosomes have distinct dynamics and are more influenced by natural selection than autosomal duplications, regardless of the kind of sex determination systems.展开更多
Strong genetic incompatibilities exist between two primary rice subspecies,indica and japonica.However,the wild ancestors of rice,O.nivara Sharma et Shastry and O.rufipogon Griff.,are genetically compatible.How this g...Strong genetic incompatibilities exist between two primary rice subspecies,indica and japonica.However,the wild ancestors of rice,O.nivara Sharma et Shastry and O.rufipogon Griff.,are genetically compatible.How this genetic incompatibility became established has not been clearly elucidated.To provide insights into the process,we analyzed a pair of hybrid sterility genes in rice,DOPPELGANGER 1(DPL1)and DOPPELGANGER 2(DPL2).Either of the two loci can have one defective allele(DPL1-and DPL2-).Hybrid pollen carrying both DPL1-and DPL2-alleles is sterile.To explore the origination of DPL1-and DPL2-,we sequenced the DPL1 and DPL2 genes of 811 individual plants,including Oryza sativa(132),O.nivara(296)and O.rufipogon(383).We then obtained 20 DPL1 and 34 DPL2 sequences of O.sativa from online databases.Using these sequences,we analyzed the genetic and geographic distribution patterns of DPL genes in modern rice and its wild ancestors.Compared with the ancestral populations,DPL1-and DPL2-showed reduced diversity but increased frequency in modern rice.We speculated that the diversity reduction was due to a historic genetic bottleneck,and the frequency had likely increased because the defective alleles were preferred following this artificial selection.Such results indicated that standing variances in ancestral lines can lead to severe incompatibilities among descendants.Haplotype analysis indicated that the DPL1-haplotype of rice emerged from an O.nivara population in India,whereas the DPL2-haplotype emerged from O.rufipogon in South China.Hence,the evolutionary history of DPLs conforms to the presumed multiple domestication events of modern rice.展开更多
The duplicate form of the generalized Gould-Hsu inversions has been obtained by Shi and Zhang. In this paper, we present a simple proof of this duplicate form. With the same method, we construct the duplicate form of ...The duplicate form of the generalized Gould-Hsu inversions has been obtained by Shi and Zhang. In this paper, we present a simple proof of this duplicate form. With the same method, we construct the duplicate form of the generalized Carlitz inversions. Using this duplicate form, we obtain several terminating basic hypergeometric identities and some limiting cases.展开更多
The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are imm...The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.展开更多
Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play ...Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-Iike genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-Iike genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leafletsl （rell） and reduced leaflets3 （rel3）, which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.展开更多
The evolution of the central nervous system（CNS） is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties,gene duplication might play an imp...The evolution of the central nervous system（CNS） is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties,gene duplication might play an important role in the functional innovation of vertebrate CNS.In this study,we focused on a group of CNS-biased genes that duplicated during early vertebrate evolution.We investigated the tempo-spatial expression patterns of 33 duplicate gene families and their orthologs during the embryonic development of the vertebrate Xenopus laevis and the cephalochordate Brachiostoma belcheri.Almost all the identified duplicate genes are differentially expressed in the CNS in Xenopus embryos,and more than 50%and 30%duplicate genes are expressed in the telencephalon and mid-hindbrain boundary,respectively,which are mostly considered as two innovations in the vertebrate CNS.Interestingly,more than 50%of the amphioxus orthologs do not show apparent expression in the CNS in amphioxus embryos as detected by in situ hybridization,indicating that some of the vertebrate CNS-biased duplicate genes might arise from non-CNS genes in invertebrates.Our data accentuate the functional contribution of gene duplication in the CNS evolution of vertebrate and uncover an invertebrate non-CNS history for some vertebrate CNS-biased duplicate genes.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
In tea plants,the abundant flavonoid compounds are responsible for the health benefits for the human body and define the astringent flavor profile.While the downstream mechanisms of flavonoid biosynthesis have been ex...In tea plants,the abundant flavonoid compounds are responsible for the health benefits for the human body and define the astringent flavor profile.While the downstream mechanisms of flavonoid biosynthesis have been extensively studied,the role of chalcone synthase(CHS)in this secondary metabolic process in tea plants remains less clear.In this study,we compared the evolutionary profile of the flavonoid metabolism pathway and discovered that gene duplication of CHS occurred in tea plants.We identified three CsCHS genes,along with a CsCHS-like gene,as potential candidates for further functional investigation.Unlike the CsCHS-like gene,the CsCHS genes effectively restored flavonoid production in Arabidopsis chs-mutants.Additionally,CsCHS transgenic tobacco plants exhibited higher flavonoid compound accumulation compared to their wild-type counterparts.Most notably,our examination of promoter and gene expression levels for the selected CHS genes revealed distinct responses to UV-B stress in tea plants.Our findings suggest that environmental factors such as UV-B exposure could have been the key drivers behind the gene duplication events in CHS.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The mai...The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.展开更多
The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2...The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,an...Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,and functional abilities.Diseases such as Alzheimer s disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis represent some of the most prominent examples of neurodegenerative disorders.Des pite scientific advancement in understanding disease pathology and prognosis,the therapeutic strategies available for management remain limited.In recent years,microRNAs,small non-coding RNA molecules,have emerged as key players in the pathogenesis of neurodegenerative disorde rs.Therefo re,understanding how these microRNAs affect disease pathology and pathway signaling is essential,and may open microRNAs as new avenues for potential therapeutic intervention.This review explores the role of microRNAs in va rious neurodegenerative diseases,discuss how microRNAs affect signaling pathways,and examine the potential of microRNAs as therapeutic targets.展开更多
Gene duplication is a major determinant of the size and gene complement of eukaryotic genomes (Lockton and Gaut, 2005). There are a number of different ways in which duplicate genes can arise (Sankoff, 2001), but
AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Com...AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
基金supported by National Institutes of Health(NIH grant R01GM054657)to A.D.C
文摘CRISPR （clustered regularly interspaced short palindromic repeats）-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 genome editing make it ideal for investigating the function of genes in vivo （Hsu et al., 2014）. Gene duplication is a key driver of evolu- tionary novelty （Taylor and Raes, 2004）. However, duplicated genes with near-identical sequences and functional redun- dancy have posed challenges for genetic analysis （Woollard, 2005）. The functions of duplicated genes can be assessed by simultaneous knockdown using homology-based methods such as RNA interference （RNAi） （Tischler et al., 2006）, Generation of double or triple mutants is an alternative way to assess functional redundancy of duplicated genes, However, generation of such compound mutants by forward or reverse genetic methods is time consuming.
基金the Ministry of Agriculture and Rural Affairs of China,the National Key R&D Program of China(2019YFA0802600)the Chinese Academy of Sciences(ZDBS-LY-SM005,XDPB17)the National Natural Science Foundation of China(31970565).
文摘Since the discovery of the first transposon by Dr.Barbara McClintock,the prevalence and diversity of transposable elements(TEs)have been gradually recognized.As fundamental genetic components,TEs drive organismal evolution not only by contributing functional sequences(e.g.,regulatory elements or“controllers”as phrased by Dr.McClintock)but also by shuffling genomic sequences.In the latter respect,TE-mediated gene duplications have contributed to the origination of new genes and attracted extensive interest.In response to the development of this field,we herein attempt to provide an overview of TEmediated duplication by focusing on common rules emerging across duplications generated by different TE types.Specifically,despite the huge divergence of transposition machinery across TEs,we identify three common features of various TE-mediated duplication mechanisms,including end bypass,template switching,and recurrent transposition.These three features lead to one common functional outcome,namely,TE-mediated duplicates tend to be subjected to exon shuffling and neofunctionalization.Therefore,the intrinsic properties of the mutational mechanism constrain the evolutionary trajectories of these duplicates.We finally discuss the future of this field including an in-depth characterization of both the duplication mechanisms and functions of TE-mediated duplicates.
基金supported by the National Science Foundation of China (No. 30600064)the National Basic Research Program of China (973 Program) (No. 2007CB815702) to X.Lu
文摘It has been shown that duplicate genes on the X chromosome evolve much faster than duplicate genes on autosomes in Drosophila melanogaster. However, whether this phenomenon is general and can be applied to other species is not known. Here we examined this issue in chicken that have heterogametic females （females have ZW sex chromosome）. We compared sequence divergence of duplicate genes on the Z chromosome with those on autosomes. We found that duplications on the Z chromosome indeed evolved faster than those on autosomes and show distinct patterns of molecular evolution from autosomal duplications. Examination of the expression of duplicate genes revealed an enrichment of duplications on the Z chromosome having male-biased expression and an enrichment of duplications on the autosomes having female-biased expression. These results suggest an evolutionary trend of the recruitment of duplicate genes towards reproduction-specific function. The faster evolution of duplications on Z than on the autosomes is most likely contributed by the selective forces driving the fixation of adaptive mutations on Z. Therefore, the common phenomena observed in both flies and chicken suggest that duplicate genes on sex chromosomes have distinct dynamics and are more influenced by natural selection than autosomal duplications, regardless of the kind of sex determination systems.
基金the Chinese Academy of Sciences(Grant Nos.XDA08020103 and XDB31000000)the National Natural Science Foundation of China(Grant Nos.31470332,91731301 and 91231201)。
文摘Strong genetic incompatibilities exist between two primary rice subspecies,indica and japonica.However,the wild ancestors of rice,O.nivara Sharma et Shastry and O.rufipogon Griff.,are genetically compatible.How this genetic incompatibility became established has not been clearly elucidated.To provide insights into the process,we analyzed a pair of hybrid sterility genes in rice,DOPPELGANGER 1(DPL1)and DOPPELGANGER 2(DPL2).Either of the two loci can have one defective allele(DPL1-and DPL2-).Hybrid pollen carrying both DPL1-and DPL2-alleles is sterile.To explore the origination of DPL1-and DPL2-,we sequenced the DPL1 and DPL2 genes of 811 individual plants,including Oryza sativa(132),O.nivara(296)and O.rufipogon(383).We then obtained 20 DPL1 and 34 DPL2 sequences of O.sativa from online databases.Using these sequences,we analyzed the genetic and geographic distribution patterns of DPL genes in modern rice and its wild ancestors.Compared with the ancestral populations,DPL1-and DPL2-showed reduced diversity but increased frequency in modern rice.We speculated that the diversity reduction was due to a historic genetic bottleneck,and the frequency had likely increased because the defective alleles were preferred following this artificial selection.Such results indicated that standing variances in ancestral lines can lead to severe incompatibilities among descendants.Haplotype analysis indicated that the DPL1-haplotype of rice emerged from an O.nivara population in India,whereas the DPL2-haplotype emerged from O.rufipogon in South China.Hence,the evolutionary history of DPLs conforms to the presumed multiple domestication events of modern rice.
文摘The duplicate form of the generalized Gould-Hsu inversions has been obtained by Shi and Zhang. In this paper, we present a simple proof of this duplicate form. With the same method, we construct the duplicate form of the generalized Carlitz inversions. Using this duplicate form, we obtain several terminating basic hypergeometric identities and some limiting cases.
文摘The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.
文摘Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-Iike genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-Iike genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leafletsl （rell） and reduced leaflets3 （rel3）, which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.
基金supported by the grants from the Innovation Project of Chinese Academy of Sciences(No.KSCX2-YW-R- 090)the Key State Research Program from the Ministry of Science and Technology of China(No.2007CB947201)
文摘The evolution of the central nervous system（CNS） is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties,gene duplication might play an important role in the functional innovation of vertebrate CNS.In this study,we focused on a group of CNS-biased genes that duplicated during early vertebrate evolution.We investigated the tempo-spatial expression patterns of 33 duplicate gene families and their orthologs during the embryonic development of the vertebrate Xenopus laevis and the cephalochordate Brachiostoma belcheri.Almost all the identified duplicate genes are differentially expressed in the CNS in Xenopus embryos,and more than 50%and 30%duplicate genes are expressed in the telencephalon and mid-hindbrain boundary,respectively,which are mostly considered as two innovations in the vertebrate CNS.Interestingly,more than 50%of the amphioxus orthologs do not show apparent expression in the CNS in amphioxus embryos as detected by in situ hybridization,indicating that some of the vertebrate CNS-biased duplicate genes might arise from non-CNS genes in invertebrates.Our data accentuate the functional contribution of gene duplication in the CNS evolution of vertebrate and uncover an invertebrate non-CNS history for some vertebrate CNS-biased duplicate genes.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金supported by the National Natural Science Foundation of China(U21A20232,32372756,and 32202551).
文摘In tea plants,the abundant flavonoid compounds are responsible for the health benefits for the human body and define the astringent flavor profile.While the downstream mechanisms of flavonoid biosynthesis have been extensively studied,the role of chalcone synthase(CHS)in this secondary metabolic process in tea plants remains less clear.In this study,we compared the evolutionary profile of the flavonoid metabolism pathway and discovered that gene duplication of CHS occurred in tea plants.We identified three CsCHS genes,along with a CsCHS-like gene,as potential candidates for further functional investigation.Unlike the CsCHS-like gene,the CsCHS genes effectively restored flavonoid production in Arabidopsis chs-mutants.Additionally,CsCHS transgenic tobacco plants exhibited higher flavonoid compound accumulation compared to their wild-type counterparts.Most notably,our examination of promoter and gene expression levels for the selected CHS genes revealed distinct responses to UV-B stress in tea plants.Our findings suggest that environmental factors such as UV-B exposure could have been the key drivers behind the gene duplication events in CHS.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
文摘The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.
基金funded by the Major Science and Technology Projects of Zhejiang Province,China(Grant No.2021C02063-5)the Key Research and Development Projects of Hainan Province,China(Grant No.ZDYF2023XDNY086)+2 种基金the State Key Laboratory for Quality and Safety Hazard Factors and Risk Prevention and Control of Agricultural Products Jointly Constructed by the Ministry and the Province,China(Grant No.2010DS700124)the Zhejiang Province Vanguard Leading Goose Project,China(Grant Nos.2023C02055 and 2022C02034)the Jiaxing Nanhu District Science and Technology Plan Project,China(Grant No.2023017).
文摘The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金1RO1EY032959-01 from NIH,Leonard A Mann Chair Endowment Fund,from the University of Dayton(to AS)Knights Templar Eye Foundation grant(to MS)。
文摘Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,and functional abilities.Diseases such as Alzheimer s disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis represent some of the most prominent examples of neurodegenerative disorders.Des pite scientific advancement in understanding disease pathology and prognosis,the therapeutic strategies available for management remain limited.In recent years,microRNAs,small non-coding RNA molecules,have emerged as key players in the pathogenesis of neurodegenerative disorde rs.Therefo re,understanding how these microRNAs affect disease pathology and pathway signaling is essential,and may open microRNAs as new avenues for potential therapeutic intervention.This review explores the role of microRNAs in va rious neurodegenerative diseases,discuss how microRNAs affect signaling pathways,and examine the potential of microRNAs as therapeutic targets.
文摘Gene duplication is a major determinant of the size and gene complement of eukaryotic genomes (Lockton and Gaut, 2005). There are a number of different ways in which duplicate genes can arise (Sankoff, 2001), but
基金Supported by the National Natural Science Foundation of China(No.81873686)Natural Science Foundation of Hunan Province(No.2023JJ30715)+4 种基金Scientific Research Project of Hunan Provincial Health Commission(No.A202303018385)Health Research Project of Hunan Provincial Health Commission(No.W20243024)Distinguished Professor of the Lotus Scholars Award Program of Hunan ProvinceSublimation Scholars Project of Central South UniversityWisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
