Soybean(Glycine max L.)is a protein and oil crop grown worldwide.Its fitness may be reduced by deleterious mutations,whose identification and purging is desirable for crop breeding.In the published whole-genome re-seq...Soybean(Glycine max L.)is a protein and oil crop grown worldwide.Its fitness may be reduced by deleterious mutations,whose identification and purging is desirable for crop breeding.In the published whole-genome re-sequenced data of 2214 soybean accessions,including 221 wild soybean,1132 landrace cultivars and 861 improved soybean lines,we identified 115,275 deleterious single-nucleotide polymorphisms(SNPs).Numbers of deleterious alleles increased from wild soybeans to landraces and decreased from landraces to modern improved lines.Genes in selective-sweep regions showed fewer deleterious mutations than the remaining genes.Deleterious mutations explained 4.3%-48%more phenotypic variation than randomly selected SNPs for resistance to soybean cyst nematode race 2(SCN2),soybean cyst nematode race 3(SCN3)and soybean mosaic virus race 3(SMV3).These findings illustrate how mutation load has shifted during soybean domestication,expansion and improvement and provide candidate sites for breeding out deleterious mutations in soybean by genome editing and/or conventional breeding focused on the selection of progeny with fewer deleterious alleles.展开更多
The calculating model for the packing degree of spherical particles system was modified. The grain grading model of cement-based materials was established and could be applied in the global grading system as well as i...The calculating model for the packing degree of spherical particles system was modified. The grain grading model of cement-based materials was established and could be applied in the global grading system as well as in the nano-fiber reinforced system. According to the grain grading model, two kinds of mortar were designed by using the global grain materials and nano-fiber materials such as fly ash, silica fume and NR powder. In this paper, the densities of two above systems cured for 90d were tested and the relationship of deleterious porosity and the total porosity of hardened mortar was discussed. Research results show that nano-fiber material such as NR powder can increase the density of cement-based materials. The relationship of deleterious porosity and the total porosity of hardened mortar accords with logarithmic curve. The deleterious porosity and the rationality of the grading can be roughly predicted through calculating the packing degree by the grain grading model of cement-based materials.展开更多
Single amino acid polymorphisms(SAPs),also known as non-synonymous single nucleotide polymorphisms(nsSNPs),are responsible for most of human genetic diseases.Discriminate the deleterious SAPs from neutral ones can hel...Single amino acid polymorphisms(SAPs),also known as non-synonymous single nucleotide polymorphisms(nsSNPs),are responsible for most of human genetic diseases.Discriminate the deleterious SAPs from neutral ones can help identify the disease genes and understand the mechanism of diseases.In this work,a method of deleterious SAP prediction at system level was established.Unlike most existing methods,our method not only considers the sequence and structure information,but also the network information.The integration of network information can improve the performance of deleterious SAP prediction.To make our method available to the public,we developed SySAP(a System-level predictor of deleterious Single Amino acid Polymorphisms),an easy-to-use and high accurate web server.SySAP is freely available at http://www.biosino.org/SySAP/and http://lifecenter.sgst.cn/SySAP/.展开更多
Endangered species generally have small populations with low genetic diversity and a high genetic load.Thuja sutchuenensis is an endangered conifer endemic to southwestern China.It was once considered extinct in the w...Endangered species generally have small populations with low genetic diversity and a high genetic load.Thuja sutchuenensis is an endangered conifer endemic to southwestern China.It was once considered extinct in the wild,but in 1999 was rediscovered.However,little is known about its genetic load.We collected 67 individuals from five wild,isolated T.sutchuenensis populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T.sutchuenensis to delineate the conservation units of T.sutchuenensis,based on whole transcriptome sequencing data,as well as target capture sequencing data.We found that populations of T.sutchuenensis could be divided into three groups.These groups had low levels genetic diversity and were moderately genetically differentiated.Our findings also indicate that T.sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum.Among Thuja species,T.sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection.However,distribution of fitness effects analysis indicated a high extinction risk for T.sutchuenensis.Multiple lines of evidence identified three management units for T.sutchuenensis.Although T.sutchuenensis possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare conifer.This might also hold true for many endangered plant species in the mountains all over the world.展开更多
The phenomena of tuyere upward-warp have been found at No.6 blast furnace in Kunming Steel Company China after its blow-in, which has made a great impact on the practical production of the furnace. Thus, a number of e...The phenomena of tuyere upward-warp have been found at No.6 blast furnace in Kunming Steel Company China after its blow-in, which has made a great impact on the practical production of the furnace. Thus, a number of efforts have been made to elucidate the mechanism of this phenomenon. The results of investigation and tests revealed that the enrichment and expansion of zinc in the tuyere bricks is the main factor leading to the tuyere upward-warp. The eroding behavior of zinc is that the inner structure of the tuyere bricks turns from dense to loose with entering, enriching and expanding of zinc, which forms spot-like→stripe-like→ditch-like→vein-like→tumorlike eroding passage. Additionally, it is found that the sequence of deleterious ele- ments entering the tuyere refractory is K, Na, Zn and Pb, respectively. Finally, the phenomena and process of zinc crystallization and growth in the refractory have been clearly observed and recorded during this investigation.展开更多
Based on the systematic analysis of the coal gangue in Weibei Coalfield, such as petrologic characteristics, chemical composition, nutrient elements, deleterious elements, and the transformation, and compared with the...Based on the systematic analysis of the coal gangue in Weibei Coalfield, such as petrologic characteristics, chemical composition, nutrient elements, deleterious elements, and the transformation, and compared with the soil element content background values of Loess Plateau and national harmful materials controlling standards, we conclude that the coal gangue in the Weibei Coalfield has huge potential to be used as clay fertilizer.展开更多
To extend the contemporary understanding into the grain yield heterosis of wheat, the current study investigated the contribution of deleterious alleles in shaping mid-parent heterosis(MPH). These alleles occur at low...To extend the contemporary understanding into the grain yield heterosis of wheat, the current study investigated the contribution of deleterious alleles in shaping mid-parent heterosis(MPH). These alleles occur at low frequency in the genome and are often missed by automated genotyping platforms like SNP arrays. The deleterious alleles herein were detected using a quantitative measurement of evolutionary conservation based on the phylogeny of wheat and investigations were made to:(1) assess the benefit of including deleterious alleles into MPH prediction models and(2) understand the genetic underpinnings of deleterious SNPs for grain yield MPH using contrasting crosses viz. elite × elite(Exp. 1) and elite × plant genetic resources(PGR;Exp. 2). In our study, we found a lower allele frequency of moderately deleterious alleles in elites compared to PGRs. This highlights the role of purifying selection for the development of elite wheat cultivars. It was shown that deleterious alleles are informative for MPH prediction models: modelling their additive-by-additive effects in Exp. 1 and dominance as well as associated digenic epistatic effects in Exp. 2 significantly boosts prediction accuracies of MPH. Furthermore,heterotic-quantitative trait loci's underlying MPH was investigated and their properties were contrasted in the two crosses. Conclusively, it was proposed that incomplete dominance of deleterious alleles contributes to grain yield heterosis in elite crosses(Exp. 1).展开更多
A genetic association between single nucleotide polymorphisms (SNPs) and pulmonary hypertension syndrome (PHS) was established in a commercial population of broiler chickens. The associated SNPs were found in the NOS3...A genetic association between single nucleotide polymorphisms (SNPs) and pulmonary hypertension syndrome (PHS) was established in a commercial population of broiler chickens. The associated SNPs were found in the NOS3 and HIF1α genes (LOD > 6;p NOS3 gene interfere with its trans-activation and transcriptional activation activities under natural hypobaric hypoxia conditions and are located in a consensus sequence that is called the hypoxia response element (HRE). SNPs located in the HIF1α gene could act as alternative cryptic splicing sites in intron six, which may stimulate non-sense mediated early decay (NMD) of the primary transcript. A fragment of intron 3 of the EDN1 gene was also evaluated, but the polymorphisms found were not associated with PHS (lod 0.001). However, further studies on the regulatory transcription sequences of EDN1 are recommended. The findings of this study indicate that intronic sequences should be included when searching for polymorphisms that produce physiological changes. Introns have transcriptional regulatory sequences or post-transcriptional control signals, which are known as cis- and trans-activation regulatory elements and are able to alter the physiological processes of hypoxia adaptation when modified. Based on these findings, it can be concluded that the inheritance pattern of PHS is autosomal overdominant and has deleterious effects that are characterized by higher penetrance in heterozygous than in homozygous animals, which prevent broiler chickens from being able to adapt to high altitudes.展开更多
Evolutionary transitions from sexual to asexual reproduction should have significant influences on genetic divergence and polymorphism at the genome level.Plant lineages with diverse reproductive systems provide oppor...Evolutionary transitions from sexual to asexual reproduction should have significant influences on genetic divergence and polymorphism at the genome level.Plant lineages with diverse reproductive systems provide opportunities to investigate this question using comparative approaches and studies of molecular evolution.We investigated evidence for differences among the transcriptomes of 19 Dioscorea species(wild yams)with diverse reproductive systems.These included sexual species,those that propagate primarily by bulbils,and those with mixed sexual and asexual reproductive modes.We examined how transitions between these reproductive systems affected between-species divergence and within-species polymorphism.Primarily asexual species exhibited a reduced efficacy of natural selection and accumulation of deleterious mutations for both divergence and polymorphism.In contrast,species with mixed reproductive strategies involving both seed and clonal reproduction showed no evidence of an increased fixation of harmful mutations at the divergence level,while an accumulation of genetic load present in polymorphism was evident.Our study indicates that the genetic consequences of evolutionary transitions from sexual to predominantly clonal reproduction is likely to depend on both the duration and extent of asexuality occurring in populations.展开更多
According to current theoretical predictions, any deleterious mutations that reduce nonsexual fitness may have a negative influence on mating success. This means that sexual selection may remove deleterious mutations ...According to current theoretical predictions, any deleterious mutations that reduce nonsexual fitness may have a negative influence on mating success. This means that sexual selection may remove deleterious mutations from the populations. Males of good genetic quality should be more successful in mating, compared to the males of lower genetic quality. As mating success is a condition dependent trait, large fractions of the genome may be a target of sexual selection and many behavioral traits are likely to be condition dependent. We manipulated the genetic quality of Drosophila subobscura males by inducing mutations with ionizing radiation and observed the effects of the obtained heterozygous mutations on male mating behavior： courtship occurrence, courtship latency, mating occurrence, latency to mating and duration of mating. We found possible effects of mutations. Females mated more frequently with male progeny of nonirradiated males and that these males courted females faster compared to the male progeny of irradiated males. Our findings indicate a possible important role of sexual selection in purging deleterious mutations.展开更多
Background:Common and rare variants of guanosine triphosphate cyclohydrolase 1(GCH1)gene may play important roles in Parkinson's disease(PD).However,there is a lack of comprehensive analysis of GCH1 genotypes,espe...Background:Common and rare variants of guanosine triphosphate cyclohydrolase 1(GCH1)gene may play important roles in Parkinson's disease(PD).However,there is a lack of comprehensive analysis of GCH1 genotypes,especially in non-coding regions.The aim of this study was to explore the genetic characteristics of GCH1,including rare and common variants in coding and non-coding regions,in a large population of PD patients in Chinese mainland,as well as the phenotypic characteristics of GCH1 variant carriers.Methods:In the first cohort of this case-control study,we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls;then in the second cohort,whole-genome sequencing was performed in sporadic late-onset PD samples(1962 patients),as well as 1279 controls.Variants at target GCH1 regions were extracted,and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test.We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset(AAO)in PD patients.Results:For coding variants,we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls(1.2%VS 0.1%,P<0.0001).In the analysis of possible regulatory variants in GCH1 non-coding regions,rs12323905(P=0.001,odds ratio=1.19,95%CI 1.07-1.32)was significantly associated with PD,and variant sets in untranslated regions and intron regions,GCH1 brain-specific expression quantitative trait loci,and two possible promoter/enhancer(GH14J054857 and GH14J054880)were suggestively associated with PD.Genotype phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO(P<0.0001),and had milder motor symptoms,milder fatigue symptoms and more autonomic nervous dysfunctions.Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers(P=0.0009).Conclusions:The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype,which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.展开更多
Conversion of potato from a tetraploid, heterozygous, vegetatively propagated crop to a diploid F1hybrid, propagated via botanical seed, would constitute a considerable advance for global agriculture,but faces multipl...Conversion of potato from a tetraploid, heterozygous, vegetatively propagated crop to a diploid F1hybrid, propagated via botanical seed, would constitute a considerable advance for global agriculture,but faces multiple challenges. One such challenge is the difficulty in inbreeding potato, which involvespurging deleterious alleles from its genome. This commentary discusses possible reasons for thisdifficulty and highlights a recent sequence-based effort to classify SNP variation, in potato germplasm,according to its deleterious potential. Tools and strategies connected to this database may facilitatedevelopment of F1 hybrids.展开更多
In non-small cell lung cancers,the non-squamous and squamous subtypes(nsqNSCLC and sqNSCLC)exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpo...In non-small cell lung cancers,the non-squamous and squamous subtypes(nsqNSCLC and sqNSCLC)exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor(ICI)-based treatments.In our inhouse training cohort(n=85),the presence of the LRP1B deleterious mutation(LRP1B-del)was associated with longer and shorter progression-free survival(PFS)on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs(P=0.040)and sqNSCLCs(P=0.014),respectively.In the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio(HR)=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del(HR=1.05,P=0.64).Conversely,sqNSCLCs without LRP1Bdel benefited more from atezolizumab(HR=0.60,P=0.002)than those with LRP1B-del(HR=1.30,P=0.31).Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1Bdel in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy alone.Our findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.展开更多
基金supported by the National Natural Science Foundation of China(32172002,32070242)Shenzhen Science and Technology Program(KQTD2016113010482651)+1 种基金Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District(RC201901-05,PT201901-19)the USDA Agricultural Research Service Research Participation Program of the Oak Ridge Institute for Science and Education(ORISE)(DE-AC05-06OR23100).
文摘Soybean(Glycine max L.)is a protein and oil crop grown worldwide.Its fitness may be reduced by deleterious mutations,whose identification and purging is desirable for crop breeding.In the published whole-genome re-sequenced data of 2214 soybean accessions,including 221 wild soybean,1132 landrace cultivars and 861 improved soybean lines,we identified 115,275 deleterious single-nucleotide polymorphisms(SNPs).Numbers of deleterious alleles increased from wild soybeans to landraces and decreased from landraces to modern improved lines.Genes in selective-sweep regions showed fewer deleterious mutations than the remaining genes.Deleterious mutations explained 4.3%-48%more phenotypic variation than randomly selected SNPs for resistance to soybean cyst nematode race 2(SCN2),soybean cyst nematode race 3(SCN3)and soybean mosaic virus race 3(SMV3).These findings illustrate how mutation load has shifted during soybean domestication,expansion and improvement and provide candidate sites for breeding out deleterious mutations in soybean by genome editing and/or conventional breeding focused on the selection of progeny with fewer deleterious alleles.
基金the Natural Science Foundation of Ningbo(Grant No.2007A610061)
文摘The calculating model for the packing degree of spherical particles system was modified. The grain grading model of cement-based materials was established and could be applied in the global grading system as well as in the nano-fiber reinforced system. According to the grain grading model, two kinds of mortar were designed by using the global grain materials and nano-fiber materials such as fly ash, silica fume and NR powder. In this paper, the densities of two above systems cured for 90d were tested and the relationship of deleterious porosity and the total porosity of hardened mortar was discussed. Research results show that nano-fiber material such as NR powder can increase the density of cement-based materials. The relationship of deleterious porosity and the total porosity of hardened mortar accords with logarithmic curve. The deleterious porosity and the rationality of the grading can be roughly predicted through calculating the packing degree by the grain grading model of cement-based materials.
基金by the National Basic Research Program of China(973 Program)(Grant Nos.2011CB910204,2010CB529206,and 2010CB912702)Research Program of the Chinese Academy of Sciences(KSCX2-EW-R-04,KSCX2-YW-R-190,2011KIP204)+3 种基金National Natural Science Foundation of China(Grant Nos.30900272 and 31070752)National Key Technology R&D Program in the 11th Five Year Plan of China(No.2008BAI64B01)National High-Tech R&D Program of China(863 Program)(Grant No.2009AA02Z304)National Scientific-Basic Special Fund(No.2009FY120100).
文摘Single amino acid polymorphisms(SAPs),also known as non-synonymous single nucleotide polymorphisms(nsSNPs),are responsible for most of human genetic diseases.Discriminate the deleterious SAPs from neutral ones can help identify the disease genes and understand the mechanism of diseases.In this work,a method of deleterious SAP prediction at system level was established.Unlike most existing methods,our method not only considers the sequence and structure information,but also the network information.The integration of network information can improve the performance of deleterious SAP prediction.To make our method available to the public,we developed SySAP(a System-level predictor of deleterious Single Amino acid Polymorphisms),an easy-to-use and high accurate web server.SySAP is freely available at http://www.biosino.org/SySAP/and http://lifecenter.sgst.cn/SySAP/.
基金This study was financially supported by National Natural Science Foundation of China(grant No.U20A2080,31622015)the Institutional Research Fund from Sichuan University(2021SCUNL102)Fundamental Research Fund for the Central Universities of China(SCU 2021D006,SCU 2022D003).
文摘Endangered species generally have small populations with low genetic diversity and a high genetic load.Thuja sutchuenensis is an endangered conifer endemic to southwestern China.It was once considered extinct in the wild,but in 1999 was rediscovered.However,little is known about its genetic load.We collected 67 individuals from five wild,isolated T.sutchuenensis populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T.sutchuenensis to delineate the conservation units of T.sutchuenensis,based on whole transcriptome sequencing data,as well as target capture sequencing data.We found that populations of T.sutchuenensis could be divided into three groups.These groups had low levels genetic diversity and were moderately genetically differentiated.Our findings also indicate that T.sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum.Among Thuja species,T.sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection.However,distribution of fitness effects analysis indicated a high extinction risk for T.sutchuenensis.Multiple lines of evidence identified three management units for T.sutchuenensis.Although T.sutchuenensis possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare conifer.This might also hold true for many endangered plant species in the mountains all over the world.
基金supported by Program for New Century Excellent Talents in University(NCET-2008-0099)
文摘The phenomena of tuyere upward-warp have been found at No.6 blast furnace in Kunming Steel Company China after its blow-in, which has made a great impact on the practical production of the furnace. Thus, a number of efforts have been made to elucidate the mechanism of this phenomenon. The results of investigation and tests revealed that the enrichment and expansion of zinc in the tuyere bricks is the main factor leading to the tuyere upward-warp. The eroding behavior of zinc is that the inner structure of the tuyere bricks turns from dense to loose with entering, enriching and expanding of zinc, which forms spot-like→stripe-like→ditch-like→vein-like→tumorlike eroding passage. Additionally, it is found that the sequence of deleterious ele- ments entering the tuyere refractory is K, Na, Zn and Pb, respectively. Finally, the phenomena and process of zinc crystallization and growth in the refractory have been clearly observed and recorded during this investigation.
文摘Based on the systematic analysis of the coal gangue in Weibei Coalfield, such as petrologic characteristics, chemical composition, nutrient elements, deleterious elements, and the transformation, and compared with the soil element content background values of Loess Plateau and national harmful materials controlling standards, we conclude that the coal gangue in the Weibei Coalfield has huge potential to be used as clay fertilizer.
基金supported by the German Federal Ministry of Food and Agriculture (FKZ2818408B18)the Federal Ministry of Education and Research of Germany (FKZ031B0184A, B)the China Scholarship Council (201906350045)。
文摘To extend the contemporary understanding into the grain yield heterosis of wheat, the current study investigated the contribution of deleterious alleles in shaping mid-parent heterosis(MPH). These alleles occur at low frequency in the genome and are often missed by automated genotyping platforms like SNP arrays. The deleterious alleles herein were detected using a quantitative measurement of evolutionary conservation based on the phylogeny of wheat and investigations were made to:(1) assess the benefit of including deleterious alleles into MPH prediction models and(2) understand the genetic underpinnings of deleterious SNPs for grain yield MPH using contrasting crosses viz. elite × elite(Exp. 1) and elite × plant genetic resources(PGR;Exp. 2). In our study, we found a lower allele frequency of moderately deleterious alleles in elites compared to PGRs. This highlights the role of purifying selection for the development of elite wheat cultivars. It was shown that deleterious alleles are informative for MPH prediction models: modelling their additive-by-additive effects in Exp. 1 and dominance as well as associated digenic epistatic effects in Exp. 2 significantly boosts prediction accuracies of MPH. Furthermore,heterotic-quantitative trait loci's underlying MPH was investigated and their properties were contrasted in the two crosses. Conclusively, it was proposed that incomplete dominance of deleterious alleles contributes to grain yield heterosis in elite crosses(Exp. 1).
文摘A genetic association between single nucleotide polymorphisms (SNPs) and pulmonary hypertension syndrome (PHS) was established in a commercial population of broiler chickens. The associated SNPs were found in the NOS3 and HIF1α genes (LOD > 6;p NOS3 gene interfere with its trans-activation and transcriptional activation activities under natural hypobaric hypoxia conditions and are located in a consensus sequence that is called the hypoxia response element (HRE). SNPs located in the HIF1α gene could act as alternative cryptic splicing sites in intron six, which may stimulate non-sense mediated early decay (NMD) of the primary transcript. A fragment of intron 3 of the EDN1 gene was also evaluated, but the polymorphisms found were not associated with PHS (lod 0.001). However, further studies on the regulatory transcription sequences of EDN1 are recommended. The findings of this study indicate that intronic sequences should be included when searching for polymorphisms that produce physiological changes. Introns have transcriptional regulatory sequences or post-transcriptional control signals, which are known as cis- and trans-activation regulatory elements and are able to alter the physiological processes of hypoxia adaptation when modified. Based on these findings, it can be concluded that the inheritance pattern of PHS is autosomal overdominant and has deleterious effects that are characterized by higher penetrance in heterozygous than in homozygous animals, which prevent broiler chickens from being able to adapt to high altitudes.
基金supported by the Top-notch Young Talents Project of Yunnan Province(YNWR-QNBJ-2019-203)the National Natural Science Foundation of China(32470394)the Key Basic Research Programof Yunnan Province(202201AS070057,202101BC070003,and 202103AC100003).
文摘Evolutionary transitions from sexual to asexual reproduction should have significant influences on genetic divergence and polymorphism at the genome level.Plant lineages with diverse reproductive systems provide opportunities to investigate this question using comparative approaches and studies of molecular evolution.We investigated evidence for differences among the transcriptomes of 19 Dioscorea species(wild yams)with diverse reproductive systems.These included sexual species,those that propagate primarily by bulbils,and those with mixed sexual and asexual reproductive modes.We examined how transitions between these reproductive systems affected between-species divergence and within-species polymorphism.Primarily asexual species exhibited a reduced efficacy of natural selection and accumulation of deleterious mutations for both divergence and polymorphism.In contrast,species with mixed reproductive strategies involving both seed and clonal reproduction showed no evidence of an increased fixation of harmful mutations at the divergence level,while an accumulation of genetic load present in polymorphism was evident.Our study indicates that the genetic consequences of evolutionary transitions from sexual to predominantly clonal reproduction is likely to depend on both the duration and extent of asexuality occurring in populations.
文摘According to current theoretical predictions, any deleterious mutations that reduce nonsexual fitness may have a negative influence on mating success. This means that sexual selection may remove deleterious mutations from the populations. Males of good genetic quality should be more successful in mating, compared to the males of lower genetic quality. As mating success is a condition dependent trait, large fractions of the genome may be a target of sexual selection and many behavioral traits are likely to be condition dependent. We manipulated the genetic quality of Drosophila subobscura males by inducing mutations with ionizing radiation and observed the effects of the obtained heterozygous mutations on male mating behavior： courtship occurrence, courtship latency, mating occurrence, latency to mating and duration of mating. We found possible effects of mutations. Females mated more frequently with male progeny of nonirradiated males and that these males courted females faster compared to the male progeny of irradiated males. Our findings indicate a possible important role of sexual selection in purging deleterious mutations.
基金This study was supported by the National Key Research and Development Program of China(2016YFC1306000,2017YFC0909100,2018YFC1312000,and 2016YFC1306501)to GJ.F,T.B.S and Y.X.X,the Central Public-Interest Scientific Institution Basal Research Fund of Chinese Academy of Medical Sciences(2018-12 M-HL-025)+3 种基金to GJ.F,the National Natural Science Foundation of China(81873785,81974202)to GJ.F and T.B.S,and Science and Technology Major Project of Hunan Provincial Science and Technology Department(2018SK1030)to GJ.F,the innovative team program from Department of Sci-ence&Technology of Hunan Province(2019RS1010)to GJ.F,and the Innovation-driven Team Project from Central South University(2020CX016)to GJ.F.
文摘Background:Common and rare variants of guanosine triphosphate cyclohydrolase 1(GCH1)gene may play important roles in Parkinson's disease(PD).However,there is a lack of comprehensive analysis of GCH1 genotypes,especially in non-coding regions.The aim of this study was to explore the genetic characteristics of GCH1,including rare and common variants in coding and non-coding regions,in a large population of PD patients in Chinese mainland,as well as the phenotypic characteristics of GCH1 variant carriers.Methods:In the first cohort of this case-control study,we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls;then in the second cohort,whole-genome sequencing was performed in sporadic late-onset PD samples(1962 patients),as well as 1279 controls.Variants at target GCH1 regions were extracted,and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test.We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset(AAO)in PD patients.Results:For coding variants,we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls(1.2%VS 0.1%,P<0.0001).In the analysis of possible regulatory variants in GCH1 non-coding regions,rs12323905(P=0.001,odds ratio=1.19,95%CI 1.07-1.32)was significantly associated with PD,and variant sets in untranslated regions and intron regions,GCH1 brain-specific expression quantitative trait loci,and two possible promoter/enhancer(GH14J054857 and GH14J054880)were suggestively associated with PD.Genotype phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO(P<0.0001),and had milder motor symptoms,milder fatigue symptoms and more autonomic nervous dysfunctions.Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers(P=0.0009).Conclusions:The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype,which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.
基金supported by the National Science Foundation Plant Genome Integrative Organismal Systems(IOS)Grant 2310230(Characterization of Haploid Induction in Potato)Grant 1956429(Variants and Recombinants without Meiosis).
文摘Conversion of potato from a tetraploid, heterozygous, vegetatively propagated crop to a diploid F1hybrid, propagated via botanical seed, would constitute a considerable advance for global agriculture,but faces multiple challenges. One such challenge is the difficulty in inbreeding potato, which involvespurging deleterious alleles from its genome. This commentary discusses possible reasons for thisdifficulty and highlights a recent sequence-based effort to classify SNP variation, in potato germplasm,according to its deleterious potential. Tools and strategies connected to this database may facilitatedevelopment of F1 hybrids.
基金supported by the National Natural Science Foundation of China (82170108, 81700092, 81871889, 82072586, 81630071)the Clinical Research Projects in Health industry of Shanghai Municipal Health Commission (202340017)+6 种基金the Foundation of the Center for Medical and Engineering Interdisciplinary Innovation, University of Shanghai for Science and Technology (2023GD-XK08Z)the National Youth Talent (to Z. Wang)Basic Research Foundation of Shanghai Chest Hospital (2020YNJCM05)the National Key Research and Development Project of China (2022YFC2505004, 2022YFC2505000)CAMS Innovation Fund for Medical Sciences (2021-1-I2M-012)CAMS Key lab of translational research on lung cancer (2018PT31035)Beijing Natural Science Foundation (7212084)
文摘In non-small cell lung cancers,the non-squamous and squamous subtypes(nsqNSCLC and sqNSCLC)exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor(ICI)-based treatments.In our inhouse training cohort(n=85),the presence of the LRP1B deleterious mutation(LRP1B-del)was associated with longer and shorter progression-free survival(PFS)on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs(P=0.040)and sqNSCLCs(P=0.014),respectively.In the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio(HR)=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del(HR=1.05,P=0.64).Conversely,sqNSCLCs without LRP1Bdel benefited more from atezolizumab(HR=0.60,P=0.002)than those with LRP1B-del(HR=1.30,P=0.31).Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1Bdel in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy alone.Our findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.
