Wheat powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that threatens wheat production worldwide.Pm12,which originated from Aegilops speltoides,a wild relative of wheat,confers str...Wheat powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that threatens wheat production worldwide.Pm12,which originated from Aegilops speltoides,a wild relative of wheat,confers strong resistance to powdery mildew and therefore has potential use in wheat breeding.Using susceptible mutants induced by gamma irradiation,we physically mapped and isolated Pm12 and showed it to be orthologous to Pm21 from Dasypyrum villosum,also a wild relative of wheat.The resistance function of Pm12 was validated via ethyl methanesulfonatemutagenesis,virus-induced gene silencing,and stable genetic transformation.Evolutionary analysis indicates that the Pm12/Pm21 loci in wheat species are relatively conserved but dynamic.Here,we demonstrated that the two orthologous genes,Pm12 and Pm21,possess differential resistance against the same set of Bgt isolates.Overexpression of the coiledcoil domains of both PM12 and PM21 induces cell death in Nicotiana benthamiana leaves.However,their full-length forms display different cell death-inducing activities caused by their distinct intramolecular interactions.Cloning of Pm12 will facilitate its application in wheat breeding programs.This study also gives new insight into two orthologous resistance genes,Pm12 and Pm21,which show different race specificities and intramolecular interaction patterns.展开更多
Myogenic regulatory factors(MRFs)serve as crucial transcription factors that regulate muscle development and differentiation.Although MRFs have been extensively studied across various species,their specific role in th...Myogenic regulatory factors(MRFs)serve as crucial transcription factors that regulate muscle development and differentiation.Although MRFs have been extensively studied across various species,their specific role in the muscle development of silver pomfret(Pampus argenteus)has not been fully understood.To elucidate the role of MRFs in the muscle development of silver pomfret,we characterized the muscle growth pattern during the rapid growth phase of this organism(60–120 days post-hatching,Dph).The analysis revealed a distinct transition in growth mechanisms:Hyperplasia dominated muscle development before 90 Dph,whereas hypertrophy became predominant thereafter.The period between 80–90 Dph was a critical transition stage in the muscle growth pattern.Subsequently,five MRF family members,namely,myogenic determination 1(MyoD1),MyoD2,myogenic factor 5(Myf5),Myf6,and myogenin(MyoG),were initially identified in silver pomfret.MRFs exhibited evolutionary conservation and were specifically expressed in the muscle of the silver pomfret.Differential expressions of MRFs were observed across various stages of rapid growth and among individuals with differing growth rates.Upon the addition of exogenous regulatory factors,insulin-like growth factor 1(IGF)-1 and transforming growth factor beta 1(TGF-β1)in vitro,MRFs exhibited the most significant upregulation in response to 100 ng/mL of IGF-1.Conversely,Myf5 demonstrated the most pronounced down-regulation at 100 ng/mL of TGF-β1.For the remaining genes,the most effective suppression was achieved with 1 ng/mL of TGF-β1.These findings indicate the crucial role played by MRFs in the regulation of muscle growth and development.This study not only provides new insights into the functional roles of MRFs in fish muscle development but also establishes a foundation for the optimization of silver pomfret aquaculture strategies through the modulation of these factors.展开更多
Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem m...Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of Leptospira interrogans serovar Lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. Subsequently, we presented a high-coverage proteome analysis of protein expression and multiple posttranslational modifications （PTMs）. Approximately 64.3% of the predicted L. interrogans proteins were cataloged by detecting 2 540 proteins. Meanwhile, a profile of multiple PTMs was concurrently established, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features. Unique eukaryotic-like features of L. interrogans protein modifications were demonstrated in both phosphorylation and arginine methylation. This systematic analysis provides not only comprehensive information of high-coverage protein expression and multiple modifications in prokaryotes but also a view suggesting that the evolutionarily primitive L. interrogans shares significant similarities in protein modification systems with eukaryotes.展开更多
Divergently-paired genes(DPGs)are minimal co-transcriptional units of clustered genes,representing over 10%of human genes.Our previous studies have shown that vertebrate DPGs are highly conserved compared to those fro...Divergently-paired genes(DPGs)are minimal co-transcriptional units of clustered genes,representing over 10%of human genes.Our previous studies have shown that vertebrate DPGs are highly conserved compared to those from invertebrates.Three critical questions remain:(1)which DPGs are conserved across vertebrates,especially among mammals and primates?(2)to what extent and precision do these paired promoters share their sequences mechanistically and stringently?and(3)how are human DPGs distributed over selected primate lineages,and what are their possible biological functional consequences?There are 1399 human DPGs(approximately 12%of all human protein-coding genes),of which 1136,1118,925,and 830 human DPGs show conservation when compared to selected primates,mammals,avians,and fish,respectively.DPGs are not only functionally enriched toward direct protein–DNA interactions and cell cycle synchronization,but also exhibit lineage association,narrow in principle toward synchronization of certain core molecular mechanisms and cellular processes.Second,the inter-transcription start site(inter-TSS)distances affect both co-expression strength and disparity between the two genes of a DPG.Finally,among primates,human-associated DPGs exhibit diversification in their co-expression patterns and gene duplication events,and are obviously involved in neural development.Comparing high-quality human reference genomes from European(T2T-CHM13)and Chinese(T2T-YAO)populations,we identified 55 and 357 DPGs unique to the former and the latter,respectively.Our findings offer novel insights into the regulatory characteristics between neighboring genes and their structure–function selection among functionally conserved gene clusters.展开更多
This study systematically rejects the long-standing notion of cospeciation as the dominant driver of codiversification between flowering plants and their specialist pollinators.Through cophylogenetic analysis of six c...This study systematically rejects the long-standing notion of cospeciation as the dominant driver of codiversification between flowering plants and their specialist pollinators.Through cophylogenetic analysis of six classical specialized pollination systems,the research finds that cospeciation events are consistently outnumbered by non-cospeciation events,such as host-switch,duplication,and association losses.The findings support a more dynamic and diffuse codiversification paradigm,highlighting the importance of considering a broader range of evolutionary events in understanding plant–pollinator codiversification.This new understanding is robust across diverse pollination systems and has significant implications for conservation strategies in the face of environmental change.展开更多
The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stre...The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stress-induced transcriptomic,metabolomic and phenotypic profiles in Gα,Gβ,and XLG-null mutants of two plant species,Arabidopsis thaliana and Marchantia polymorpha,and showed that G protein mediates the shift of transcriptional and metabolic homeostasis to stress readiness status.We demonstrated that such stress readiness serves as an intrinsic protection mechanism against further stressors through enhancing the phenylpropanoid pathway and abscisic acid responses.Furthermore,WRKY transcription factors were identified as key intermediates of G protein-mediated homeostatic shifts.Statistical and mathematical model comparisons between A.thaliana and M.polymorpha revealed evolutionary conservation of transcriptional and metabolic networks over land plant evolution,whereas divergence has occurred in the function of plant-specific atypical XLG subunit.Taken together,our results indicate that the shifts in transcriptional and metabolic homeostasis at least partially act as the mechanisms of G protein-coupled stress responses that are conserved between two distantly related plants.展开更多
NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classif...NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2 . The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene;the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1 , NKX2-2 , and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value.展开更多
In insects,the odorant receptor(OR)multigene family evolves by the birth-and-death evolutionary model,according to which the OR repertoire of each species has undergone specific gene gains and losses depending on thei...In insects,the odorant receptor(OR)multigene family evolves by the birth-and-death evolutionary model,according to which the OR repertoire of each species has undergone specific gene gains and losses depending on their chemical environment,resulting in taxon-specific OR lineage radiations with different sizes in the phylogenetic trees.Despite the general divergence in the gene family across different insect orders,the ORs in moths seem to be genetically conserved across species,clustered into 23 major clades containing multiple orthologous groups with single-copy gene from each species.We hypothesized that ORs in these orthologous groups are tuned to ecologically important compounds and functionally conserved.cis-Jasmone is one of the compounds that not only primes the plant defense of neighboring receiver plants,but also functions as a behavior regulator to various insects.To test our hypothesis,using Xenopus oocyte recordings,we functionally assayed the orthologues of BmorOR56,which has been characterized as a specific receptor for cis-jasmone.Our results showed highly conserved response specificity of the BmorOR56 orthologues,with all receptors within this group exclusively responding to cis-jasmone.This is supported by the dN/dS analysis,showing that strong purifying selection is acting on this group.Moreover,molecular docking showed that the ligand binding pockets of BmorOR56 orthologues to cis-jasmone are similar.Taken together,our results suggest the high conservation of OR for ecologically important compounds across Heterocera.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
基金supported by grants from the National Natural Science Foundation of China(32171990,32072053,31971874,31872009,and U1604116)the Key Research and Development Program of Zhenjiang(NY2021001)+3 种基金the State Key Laboratory of Plant Cell and Chromosome Engineering(PCCE-KF-2021-05,PCCE-KF-2022-07)the State Key Laboratory of Crop Biology in Shandong Agricultural University(2021KF01)the Taishan Scholars Project(tsqn201812123)the Key Research and Development Program of Yantai(2019YT06000470).
文摘Wheat powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that threatens wheat production worldwide.Pm12,which originated from Aegilops speltoides,a wild relative of wheat,confers strong resistance to powdery mildew and therefore has potential use in wheat breeding.Using susceptible mutants induced by gamma irradiation,we physically mapped and isolated Pm12 and showed it to be orthologous to Pm21 from Dasypyrum villosum,also a wild relative of wheat.The resistance function of Pm12 was validated via ethyl methanesulfonatemutagenesis,virus-induced gene silencing,and stable genetic transformation.Evolutionary analysis indicates that the Pm12/Pm21 loci in wheat species are relatively conserved but dynamic.Here,we demonstrated that the two orthologous genes,Pm12 and Pm21,possess differential resistance against the same set of Bgt isolates.Overexpression of the coiledcoil domains of both PM12 and PM21 induces cell death in Nicotiana benthamiana leaves.However,their full-length forms display different cell death-inducing activities caused by their distinct intramolecular interactions.Cloning of Pm12 will facilitate its application in wheat breeding programs.This study also gives new insight into two orthologous resistance genes,Pm12 and Pm21,which show different race specificities and intramolecular interaction patterns.
基金the National Key R&D Program of China(No.2022YFD2400103)the Major Project of Science,Technology and Innovation 2025 in Ningbo City(No.2021Z003)+3 种基金the Public Welfare Program of Ningbo City(Science and Technology Special Commissioner Project)(No.2022S204)the General Scientific Research Projects of Zhejiang Provincial Department of Education(No.Y202249062)the National Natural Science Foundation of China(No.42306114)the KC Wong Magna Fund in Ningbo University。
文摘Myogenic regulatory factors(MRFs)serve as crucial transcription factors that regulate muscle development and differentiation.Although MRFs have been extensively studied across various species,their specific role in the muscle development of silver pomfret(Pampus argenteus)has not been fully understood.To elucidate the role of MRFs in the muscle development of silver pomfret,we characterized the muscle growth pattern during the rapid growth phase of this organism(60–120 days post-hatching,Dph).The analysis revealed a distinct transition in growth mechanisms:Hyperplasia dominated muscle development before 90 Dph,whereas hypertrophy became predominant thereafter.The period between 80–90 Dph was a critical transition stage in the muscle growth pattern.Subsequently,five MRF family members,namely,myogenic determination 1(MyoD1),MyoD2,myogenic factor 5(Myf5),Myf6,and myogenin(MyoG),were initially identified in silver pomfret.MRFs exhibited evolutionary conservation and were specifically expressed in the muscle of the silver pomfret.Differential expressions of MRFs were observed across various stages of rapid growth and among individuals with differing growth rates.Upon the addition of exogenous regulatory factors,insulin-like growth factor 1(IGF)-1 and transforming growth factor beta 1(TGF-β1)in vitro,MRFs exhibited the most significant upregulation in response to 100 ng/mL of IGF-1.Conversely,Myf5 demonstrated the most pronounced down-regulation at 100 ng/mL of TGF-β1.For the remaining genes,the most effective suppression was achieved with 1 ng/mL of TGF-β1.These findings indicate the crucial role played by MRFs in the regulation of muscle growth and development.This study not only provides new insights into the functional roles of MRFs in fish muscle development but also establishes a foundation for the optimization of silver pomfret aquaculture strategies through the modulation of these factors.
文摘Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of Leptospira interrogans serovar Lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. Subsequently, we presented a high-coverage proteome analysis of protein expression and multiple posttranslational modifications （PTMs）. Approximately 64.3% of the predicted L. interrogans proteins were cataloged by detecting 2 540 proteins. Meanwhile, a profile of multiple PTMs was concurrently established, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features. Unique eukaryotic-like features of L. interrogans protein modifications were demonstrated in both phosphorylation and arginine methylation. This systematic analysis provides not only comprehensive information of high-coverage protein expression and multiple modifications in prokaryotes but also a view suggesting that the evolutionarily primitive L. interrogans shares significant similarities in protein modification systems with eukaryotes.
基金supported by the National Key R&D Program of China(Grant No.2023YFC2605700 to Wenming Zhao)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB38050300 to Wenming Zhao).
文摘Divergently-paired genes(DPGs)are minimal co-transcriptional units of clustered genes,representing over 10%of human genes.Our previous studies have shown that vertebrate DPGs are highly conserved compared to those from invertebrates.Three critical questions remain:(1)which DPGs are conserved across vertebrates,especially among mammals and primates?(2)to what extent and precision do these paired promoters share their sequences mechanistically and stringently?and(3)how are human DPGs distributed over selected primate lineages,and what are their possible biological functional consequences?There are 1399 human DPGs(approximately 12%of all human protein-coding genes),of which 1136,1118,925,and 830 human DPGs show conservation when compared to selected primates,mammals,avians,and fish,respectively.DPGs are not only functionally enriched toward direct protein–DNA interactions and cell cycle synchronization,but also exhibit lineage association,narrow in principle toward synchronization of certain core molecular mechanisms and cellular processes.Second,the inter-transcription start site(inter-TSS)distances affect both co-expression strength and disparity between the two genes of a DPG.Finally,among primates,human-associated DPGs exhibit diversification in their co-expression patterns and gene duplication events,and are obviously involved in neural development.Comparing high-quality human reference genomes from European(T2T-CHM13)and Chinese(T2T-YAO)populations,we identified 55 and 357 DPGs unique to the former and the latter,respectively.Our findings offer novel insights into the regulatory characteristics between neighboring genes and their structure–function selection among functionally conserved gene clusters.
基金supported by the Distinguished Youth Scholar of Yunnan Province,China(202201AV070007)the National Natural Science Foundation of China(32371701,32250410312)+2 种基金the Yunnan Revitalization Talent Support Program,Young Talent Project,the Youth Innovation Promotion Association of CAS(2020392)the 14th Five-Year Plan of XTBG,CAS(E3ZKFF3B)the CAS Key Laboratory of Tropical Forest Ecology(O9KF001B04).
文摘This study systematically rejects the long-standing notion of cospeciation as the dominant driver of codiversification between flowering plants and their specialist pollinators.Through cophylogenetic analysis of six classical specialized pollination systems,the research finds that cospeciation events are consistently outnumbered by non-cospeciation events,such as host-switch,duplication,and association losses.The findings support a more dynamic and diffuse codiversification paradigm,highlighting the importance of considering a broader range of evolutionary events in understanding plant–pollinator codiversification.This new understanding is robust across diverse pollination systems and has significant implications for conservation strategies in the face of environmental change.
基金This study was supported by the Agency for Science,Technology and Research(A*STAR)Singapore under the Industry Alignment Fund Pre-positioning Program,the High Performance Precision Agriculture(HiPPA)system(A19E4a0101)the Singapore-MIT Aliance for Research and Technology,and Disruptive&Sustainable Technologies for Agricul-tural Precision(DISTAP)(to D.U.)a discovery grant from the Natural Sciences and Engineering Research Council of Canada(ARGPIN-2020-07097)(to K-LL)。
文摘The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stress-induced transcriptomic,metabolomic and phenotypic profiles in Gα,Gβ,and XLG-null mutants of two plant species,Arabidopsis thaliana and Marchantia polymorpha,and showed that G protein mediates the shift of transcriptional and metabolic homeostasis to stress readiness status.We demonstrated that such stress readiness serves as an intrinsic protection mechanism against further stressors through enhancing the phenylpropanoid pathway and abscisic acid responses.Furthermore,WRKY transcription factors were identified as key intermediates of G protein-mediated homeostatic shifts.Statistical and mathematical model comparisons between A.thaliana and M.polymorpha revealed evolutionary conservation of transcriptional and metabolic networks over land plant evolution,whereas divergence has occurred in the function of plant-specific atypical XLG subunit.Taken together,our results indicate that the shifts in transcriptional and metabolic homeostasis at least partially act as the mechanisms of G protein-coupled stress responses that are conserved between two distantly related plants.
文摘NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2 . The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene;the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1 , NKX2-2 , and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value.
基金supported by grants from the National Natural Science Foundation of China(Grant No.32202307,32130089)Shenzhen Science and Technology Program(Grant No.KQTD20180411143628272)+1 种基金Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District(Grant No.PT202101-02)the China Postdoctoral Science Foundation(Grant No.2021M703548).
文摘In insects,the odorant receptor(OR)multigene family evolves by the birth-and-death evolutionary model,according to which the OR repertoire of each species has undergone specific gene gains and losses depending on their chemical environment,resulting in taxon-specific OR lineage radiations with different sizes in the phylogenetic trees.Despite the general divergence in the gene family across different insect orders,the ORs in moths seem to be genetically conserved across species,clustered into 23 major clades containing multiple orthologous groups with single-copy gene from each species.We hypothesized that ORs in these orthologous groups are tuned to ecologically important compounds and functionally conserved.cis-Jasmone is one of the compounds that not only primes the plant defense of neighboring receiver plants,but also functions as a behavior regulator to various insects.To test our hypothesis,using Xenopus oocyte recordings,we functionally assayed the orthologues of BmorOR56,which has been characterized as a specific receptor for cis-jasmone.Our results showed highly conserved response specificity of the BmorOR56 orthologues,with all receptors within this group exclusively responding to cis-jasmone.This is supported by the dN/dS analysis,showing that strong purifying selection is acting on this group.Moreover,molecular docking showed that the ligand binding pockets of BmorOR56 orthologues to cis-jasmone are similar.Taken together,our results suggest the high conservation of OR for ecologically important compounds across Heterocera.
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.
