The high-affinity K＋ （HAK） transporter gene family is the largest family in plant that functions as potassium transporter and is important for various aspects of plant life. In the present study, we identified 27 m...The high-affinity K＋ （HAK） transporter gene family is the largest family in plant that functions as potassium transporter and is important for various aspects of plant life. In the present study, we identified 27 members of this family in rice genome. The phylogenetic tree divided the land plant HAK transporter proteins into 6 distinct groups. Although the main characteristic of this family was established before the origin of seed plants, they also showed some differences between the members of non-seed and seed plants. The HAK genes in rice were found to have expanded in lineage-specific manner after the split of monocots and dicots, and both segmental duplication events and tandem duplication events contributed to the expansion of this family. Functional divergence analysis for this family provided statistical evidence for shifted evolutionary rate after gene duplication. Further analysis indicated that both point mutant with positive selection and gene conversion events contributed to the evolution of this family in rice.展开更多
Grass carp reovirus(GCRV)-induced gene 1(Gig1)is identified initially in crucian carp C.auratus as a novel interferon-stimulated gene(ISG)encoding an antiviral protein and subsequently as the founder member of Gig1 ge...Grass carp reovirus(GCRV)-induced gene 1(Gig1)is identified initially in crucian carp C.auratus as a novel interferon-stimulated gene(ISG)encoding an antiviral protein and subsequently as the founder member of Gig1 gene family.However,the evolution and function of Gig1 family members remain largely unknown.In this study,genome-wide searchs of 100 vertebrate species representing the main taxonomic lineages revealed that the Gig1 family originated from a common ancestor of bony fish but was completely lost in tetrapods.The Gig1 family is divided into three subfamilies,each with its own characteristics in gain and loss.Compared to subfamily Ⅰ that originated the earliest and showed no significant change in gene copies,subfamilies Ⅱ and Ⅲ were expanded robustly with teleost radiation.Despite no known domains having been identified,motif prediction revealed a conserved motif arrangement in all Gig1 family proteins.Functionally,both zebrafish and grass carp have subfamilies Ⅰ and Ⅱ but not subfamily Ⅲ.However,only certain subfamily Ⅱ genes were highly induced by viral infection and thus capable of inhibiting viral replication by overexpression and knockout assays.The Japanese rice fish medaka has no subfamily Ⅱ and,strikingly,one subfamily Ⅲ gene acquired antiviral feature.Site-directed mutation showed that three leucine residues conserved in the motif 1 were essential for the antiviral role of subfamily Ⅱ genes in zebrafish.In summary,our results indicate that bony fish-specific Gig1 gene family has been undergoing diversification in expression and function toward virus infection in a given species.展开更多
Apolipoprotein D(ApoD),a member of the lipocalin superfamily of proteins,is involved in lipid transport and stress resistance.Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates,t...Apolipoprotein D(ApoD),a member of the lipocalin superfamily of proteins,is involved in lipid transport and stress resistance.Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates,there are typically several ApoD-like genes in insects.To date,there have been relatively few studies that have examined the evolution and functional differentiation of ApoD-like genes in insects,particularly hemi-metabolous insects.In this study,we identified 10 ApoD-like genes(NlApoD1−10)with distinct spatiotemporal expression patterns in Nilaparvata lugens(BPH),which is an important pest of rice.NlApoD1−10 were found to be distributed on 3 chromosomes in a tandem array of NlApoD1/2,NlApoD3−5,and NlApoD7/8,and show sequence and gene structural divergence in the coding regions,indicating that multiple gene duplication events occurred during evolution.Phylogenetic analysis revealed that NlApoD1−10 can be clustered into 5 clades,with NlApoD3−5 and NlApoD7/8 potentially evolving exclusively in the Delphacidae family.Functional screening using an RNA interference approach revealed that only NlApoD2 was essential for BPH development and survival,whereas NlApoD4/5 are highly expressed in testes,and might play roles in reproduction.Moreover,stress response analysis revealed that NlApoD3−5/9,NlApoD3−5,and NlApoD9 were up-regulated after treatment with lipopolysaccharide,H2O2,and ultraviolet-C,respectively,indicating their potential roles in stress resistance.展开更多
OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally div...OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.展开更多
As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occur...As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.展开更多
In many interesting physical examples, the partition function is divergent, as first pointed out in 1924 by Fermi (for the hydrogen-atom case). Thus, the usual toolbox of statistical mechanics becomes unavailable, not...In many interesting physical examples, the partition function is divergent, as first pointed out in 1924 by Fermi (for the hydrogen-atom case). Thus, the usual toolbox of statistical mechanics becomes unavailable, notwithstanding the well-known fact that the pertinent system may appear to be in a thermal steady state. We tackle and overcome these difficulties hereby appeal to firmly established but not too well-known mathematical recipes and obtain finite values for a typical divergent partition function, that of a Brownian particle in an external field. This allows not only for calculating thermodynamic observables of interest, but for also instantiating other kinds of statistical mechanics’ novelties.展开更多
Background In the riverine riparian ecosystem,particularly in India,the knowledge of the effects of habitat disturbance on taxonomic distinctness,functional diversity,and local contribution toβdiversity(LCBD)of spide...Background In the riverine riparian ecosystem,particularly in India,the knowledge of the effects of habitat disturbance on taxonomic distinctness,functional diversity,and local contribution toβdiversity(LCBD)of spider community is elusive.The present study examined the relationships between the index of taxonomic distinctness(Δ^(+)),index of variation in taxonomic distinctness(λ^(+)),functional evenness(FEve),functional divergence(FDiv),functional dispersion(FDis),and LCBD of spider community of the Ganga River and the effects of habitat disturbance on these indices.A total of 27 sampling sites were selected along the bank of the Ganga River.Based on the rating of the disturbance scores,the sites were classified into lowly,moderately,and highly disturbed sites.To understand the relationships between species richness,Δ^(+),λ^(+),FDis,FDiv,FEve,LCBD,and habitat disturbance score,Pearson’s correlation was calculated,followed by the linear regression model.The one-way multivariate analysis of variance was used to find differences in taxonomic distinctness and functional diversity in the different disturbed sites.Results Significant relationships were found betweenλ^(+)andΔ^(+),FDis andΔ^(+),FDis andλ^(+),FDiv and species richness,FEve and species richness,FEve andλ^(+),FEve and habitat disturbance,LCBD and FEve,and LCBD and habitat disturbance.A significant difference was present in the indices of functional diversity between the lowly,moderately,and highly disturbed sites.Agriculture,garbage dump,human settlement,and created embankment influenced the spider community’sλ^(+),FEve,and LCBD.Conclusion Unrestrained anthropogenic activities exacerbate habitat disturbance by affecting ecological processes.Thus,understanding linkages between ecosystem disturbance,taxonomic,functional,andβdiversity can be fundamental to managing and conserving natural resources.This work highlights the importance of including taxonomic and functional diversity to comprehend the impact of habitat disturbance on riverine riparian spiders beyond just the number of species.An integrated taxonomic and functional diversity approach coupled withβdiversity can be used to support environmental assessment,restoration,and conservation planning of the biological resources of the Ganges River.展开更多
This article demonstrates a catalytic method for C(aryl)-C(alkyl) bond functionalization of N-sulfonyl amines. A cobalt(III)catalyst was used to cleave the C-C bond via β-carbon elimination, providing a metallacycle ...This article demonstrates a catalytic method for C(aryl)-C(alkyl) bond functionalization of N-sulfonyl amines. A cobalt(III)catalyst was used to cleave the C-C bond via β-carbon elimination, providing a metallacycle intermediate. Subsequent allylation,amidation, or alkenylation of the intermediate led to divergent conversions in the presence of diverse coupling partners. when the coupling partner was a diene, an insertion-type functionalization was realized with an exclusive 1,3-regioselectivity, in which both of the fragments derived from N-sulfonyl amines were utilized.展开更多
Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evoluti...Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evolution.In this study,we identified 218 functional genes and 48 pseudogenes from 114 species that span all four Cetartiodactyla lineages:two herbivorous lineages(Ruminantia and Tylopoda)and two non-herbivorous lineages(Cetancodonta and Suoidea).Multiple RNase1 genes were detected in all species of the two herbivorous lineages,and phylogenetic and genomic location analyses demonstrated that independent gene duplication events occurred in Ruminantia and Tylopoda.In Ruminantia,the gene duplication events occurred in the ancestral branches of the lineage in theMiddle Eocene,a time of increasing climatic seasonality during which Ruminantia rapidly radiated.In contrast,only a single RNase1 gene was observed in the species of the two non-herbivorous lineages(Cetancodonta and Suoidea),suggesting that the previous Cetacea-specific loss hypothesis should be rejected.Moreover,the duplicated genes of RNase1 in the two herbivorous lineages(Ruminantia and Tylopoda)may have undergone functional divergence.In combination with the temporal coincidence between gene replication and the enhanced climatic seasonality during theMiddle Eocene,this functional divergence suggests that RNase1 gene duplication was beneficial for Ruminantia to use the limited quantities of sparse fibrous vegetation and adapt to seasonal changes in climate.In summary,the findings indicate a complex and intriguing evolutionary pattern of RNase1 in Cetartiodactyla and demonstrate the molecular mechanisms by which organisms adapt to the environment.展开更多
Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar struct...Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar structures and drug-binding pockets. To identify targctablc differences between paralogs, we analyzed two types （type-I and type-ll） of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors （GPCRs） at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor （GCGR） and glucagon-like peptide-I receptor （GLP-I R）, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-ll alnino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR. which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-IR. The divergent features between GCGR and GLP-I R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.展开更多
Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect linea...Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect lineage have not been thoroughly explored.Here,we found that a lineage-specific expansion of the lipocalin genes in Lepidoptera occurred in large part due to tandem duplication events and several lipocalin genes involving insect coloration were expanded more via tandem duplication in butterflies.A comparative analysis of conserved motifs showed both conservation and divergence of lepidopteran lipocalin family protein structures during evolution.We observe dynamic changes in tissue expression preference of paralogs in Bombyx mori,suggesting differential contribution of paralogs to specific organ functions during evolution.Subcellular localization experiments revealed that lipocalins localize to the cytoplasm,nuclear membrane,or nucleus in BmN cells.Moreover,several lipocalin genes exhibited divergent responses to abiotic and biotic stresses,and 1 lipocalin gene was upregulated by 30o fold in B.mori.These results suggest that lipocalins act as signaling components in defense responses by mediating crosstalk between abiotic and biotic stress responses.This study deepens our understanding of the comprehensive characteristics of lipocalins in insects.展开更多
基金supported by the National Basic Research Program of China (No. 2006CB101700)the National High- tech Research and Development Program (No. 2006AA10Z165)the Program for New Century Excellent Talents in Uni-versity of China (No. NCET2005-05- 0502).
文摘The high-affinity K＋ （HAK） transporter gene family is the largest family in plant that functions as potassium transporter and is important for various aspects of plant life. In the present study, we identified 27 members of this family in rice genome. The phylogenetic tree divided the land plant HAK transporter proteins into 6 distinct groups. Although the main characteristic of this family was established before the origin of seed plants, they also showed some differences between the members of non-seed and seed plants. The HAK genes in rice were found to have expanded in lineage-specific manner after the split of monocots and dicots, and both segmental duplication events and tandem duplication events contributed to the expansion of this family. Functional divergence analysis for this family provided statistical evidence for shifted evolutionary rate after gene duplication. Further analysis indicated that both point mutant with positive selection and gene conversion events contributed to the evolution of this family in rice.
基金supported by grants from the National Key R&D Program of China(2022YFF1000302)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0730100)+1 种基金the National Natural Science Foundation of China(32473197,32403073,32202978)the Ministry of Science and Technology of China(grant number:2023ZD04065).
文摘Grass carp reovirus(GCRV)-induced gene 1(Gig1)is identified initially in crucian carp C.auratus as a novel interferon-stimulated gene(ISG)encoding an antiviral protein and subsequently as the founder member of Gig1 gene family.However,the evolution and function of Gig1 family members remain largely unknown.In this study,genome-wide searchs of 100 vertebrate species representing the main taxonomic lineages revealed that the Gig1 family originated from a common ancestor of bony fish but was completely lost in tetrapods.The Gig1 family is divided into three subfamilies,each with its own characteristics in gain and loss.Compared to subfamily Ⅰ that originated the earliest and showed no significant change in gene copies,subfamilies Ⅱ and Ⅲ were expanded robustly with teleost radiation.Despite no known domains having been identified,motif prediction revealed a conserved motif arrangement in all Gig1 family proteins.Functionally,both zebrafish and grass carp have subfamilies Ⅰ and Ⅱ but not subfamily Ⅲ.However,only certain subfamily Ⅱ genes were highly induced by viral infection and thus capable of inhibiting viral replication by overexpression and knockout assays.The Japanese rice fish medaka has no subfamily Ⅱ and,strikingly,one subfamily Ⅲ gene acquired antiviral feature.Site-directed mutation showed that three leucine residues conserved in the motif 1 were essential for the antiviral role of subfamily Ⅱ genes in zebrafish.In summary,our results indicate that bony fish-specific Gig1 gene family has been undergoing diversification in expression and function toward virus infection in a given species.
基金This work was supported by the Natural Science Foundation of Zhejiang Province(LQ22C140001)the National Natural Science Foundation of China(32230086).
文摘Apolipoprotein D(ApoD),a member of the lipocalin superfamily of proteins,is involved in lipid transport and stress resistance.Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates,there are typically several ApoD-like genes in insects.To date,there have been relatively few studies that have examined the evolution and functional differentiation of ApoD-like genes in insects,particularly hemi-metabolous insects.In this study,we identified 10 ApoD-like genes(NlApoD1−10)with distinct spatiotemporal expression patterns in Nilaparvata lugens(BPH),which is an important pest of rice.NlApoD1−10 were found to be distributed on 3 chromosomes in a tandem array of NlApoD1/2,NlApoD3−5,and NlApoD7/8,and show sequence and gene structural divergence in the coding regions,indicating that multiple gene duplication events occurred during evolution.Phylogenetic analysis revealed that NlApoD1−10 can be clustered into 5 clades,with NlApoD3−5 and NlApoD7/8 potentially evolving exclusively in the Delphacidae family.Functional screening using an RNA interference approach revealed that only NlApoD2 was essential for BPH development and survival,whereas NlApoD4/5 are highly expressed in testes,and might play roles in reproduction.Moreover,stress response analysis revealed that NlApoD3−5/9,NlApoD3−5,and NlApoD9 were up-regulated after treatment with lipopolysaccharide,H2O2,and ultraviolet-C,respectively,indicating their potential roles in stress resistance.
基金supported by the National Key Research and Development Program of China(2016YFD0500202)the National Natural Science Foundation of China(31772587)the Plan 111(B12008)。
文摘OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.
文摘As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.
文摘In many interesting physical examples, the partition function is divergent, as first pointed out in 1924 by Fermi (for the hydrogen-atom case). Thus, the usual toolbox of statistical mechanics becomes unavailable, notwithstanding the well-known fact that the pertinent system may appear to be in a thermal steady state. We tackle and overcome these difficulties hereby appeal to firmly established but not too well-known mathematical recipes and obtain finite values for a typical divergent partition function, that of a Brownian particle in an external field. This allows not only for calculating thermodynamic observables of interest, but for also instantiating other kinds of statistical mechanics’ novelties.
基金National Mission for Clean Ganga(NMCG),Ministry of Jal Shakti,Government of India(Grant No.B-02/2015-16/1259/NMCG-WII PROPOSAL and B-03/2015-16/1077/NMCG-NEW PROPASAL).
文摘Background In the riverine riparian ecosystem,particularly in India,the knowledge of the effects of habitat disturbance on taxonomic distinctness,functional diversity,and local contribution toβdiversity(LCBD)of spider community is elusive.The present study examined the relationships between the index of taxonomic distinctness(Δ^(+)),index of variation in taxonomic distinctness(λ^(+)),functional evenness(FEve),functional divergence(FDiv),functional dispersion(FDis),and LCBD of spider community of the Ganga River and the effects of habitat disturbance on these indices.A total of 27 sampling sites were selected along the bank of the Ganga River.Based on the rating of the disturbance scores,the sites were classified into lowly,moderately,and highly disturbed sites.To understand the relationships between species richness,Δ^(+),λ^(+),FDis,FDiv,FEve,LCBD,and habitat disturbance score,Pearson’s correlation was calculated,followed by the linear regression model.The one-way multivariate analysis of variance was used to find differences in taxonomic distinctness and functional diversity in the different disturbed sites.Results Significant relationships were found betweenλ^(+)andΔ^(+),FDis andΔ^(+),FDis andλ^(+),FDiv and species richness,FEve and species richness,FEve andλ^(+),FEve and habitat disturbance,LCBD and FEve,and LCBD and habitat disturbance.A significant difference was present in the indices of functional diversity between the lowly,moderately,and highly disturbed sites.Agriculture,garbage dump,human settlement,and created embankment influenced the spider community’sλ^(+),FEve,and LCBD.Conclusion Unrestrained anthropogenic activities exacerbate habitat disturbance by affecting ecological processes.Thus,understanding linkages between ecosystem disturbance,taxonomic,functional,andβdiversity can be fundamental to managing and conserving natural resources.This work highlights the importance of including taxonomic and functional diversity to comprehend the impact of habitat disturbance on riverine riparian spiders beyond just the number of species.An integrated taxonomic and functional diversity approach coupled withβdiversity can be used to support environmental assessment,restoration,and conservation planning of the biological resources of the Ganges River.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2022SDXHDX0006)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(2020R01004)。
文摘This article demonstrates a catalytic method for C(aryl)-C(alkyl) bond functionalization of N-sulfonyl amines. A cobalt(III)catalyst was used to cleave the C-C bond via β-carbon elimination, providing a metallacycle intermediate. Subsequent allylation,amidation, or alkenylation of the intermediate led to divergent conversions in the presence of diverse coupling partners. when the coupling partner was a diene, an insertion-type functionalization was realized with an exclusive 1,3-regioselectivity, in which both of the fragments derived from N-sulfonyl amines were utilized.
基金supported by the Special Basic Cooperative Research Programs of Yunnan Province Youth Academic and Technical Leaders Reserve Talent(202405AC350082)Yunnan Provincial Undergraduate Universities’Association(202101BA070001-068).
文摘Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evolution.In this study,we identified 218 functional genes and 48 pseudogenes from 114 species that span all four Cetartiodactyla lineages:two herbivorous lineages(Ruminantia and Tylopoda)and two non-herbivorous lineages(Cetancodonta and Suoidea).Multiple RNase1 genes were detected in all species of the two herbivorous lineages,and phylogenetic and genomic location analyses demonstrated that independent gene duplication events occurred in Ruminantia and Tylopoda.In Ruminantia,the gene duplication events occurred in the ancestral branches of the lineage in theMiddle Eocene,a time of increasing climatic seasonality during which Ruminantia rapidly radiated.In contrast,only a single RNase1 gene was observed in the species of the two non-herbivorous lineages(Cetancodonta and Suoidea),suggesting that the previous Cetacea-specific loss hypothesis should be rejected.Moreover,the duplicated genes of RNase1 in the two herbivorous lineages(Ruminantia and Tylopoda)may have undergone functional divergence.In combination with the temporal coincidence between gene replication and the enhanced climatic seasonality during theMiddle Eocene,this functional divergence suggests that RNase1 gene duplication was beneficial for Ruminantia to use the limited quantities of sparse fibrous vegetation and adapt to seasonal changes in climate.In summary,the findings indicate a complex and intriguing evolutionary pattern of RNase1 in Cetartiodactyla and demonstrate the molecular mechanisms by which organisms adapt to the environment.
基金supported by a grant from the National Natural Science Foundation of China(Grant No.31571355 and 31301034)supported by Fudan University,ChinaIowa State University,United States
文摘Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar structures and drug-binding pockets. To identify targctablc differences between paralogs, we analyzed two types （type-I and type-ll） of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors （GPCRs） at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor （GCGR） and glucagon-like peptide-I receptor （GLP-I R）, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-ll alnino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR. which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-IR. The divergent features between GCGR and GLP-I R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.
基金supported by the National Natural Science Foundation of China(grant no.31970460,32170483)the Natural Science Foundation of Zhejiang Province(grant no.LR22C040001)+1 种基金the Zhejiang Provincial Science and Technology Plans(2021C02072-6)the Zhejiang Provincial Key Laboratory Construction Plans(2020E10025).
文摘Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect lineage have not been thoroughly explored.Here,we found that a lineage-specific expansion of the lipocalin genes in Lepidoptera occurred in large part due to tandem duplication events and several lipocalin genes involving insect coloration were expanded more via tandem duplication in butterflies.A comparative analysis of conserved motifs showed both conservation and divergence of lepidopteran lipocalin family protein structures during evolution.We observe dynamic changes in tissue expression preference of paralogs in Bombyx mori,suggesting differential contribution of paralogs to specific organ functions during evolution.Subcellular localization experiments revealed that lipocalins localize to the cytoplasm,nuclear membrane,or nucleus in BmN cells.Moreover,several lipocalin genes exhibited divergent responses to abiotic and biotic stresses,and 1 lipocalin gene was upregulated by 30o fold in B.mori.These results suggest that lipocalins act as signaling components in defense responses by mediating crosstalk between abiotic and biotic stress responses.This study deepens our understanding of the comprehensive characteristics of lipocalins in insects.
