Genome-wide scans to detect positive selection in Large White and Tongcheng pigs
Xiuling Li*,Songbai Yang*,Zhonglin Tang ?,Kui Li ?,Max F.Rothschild ?,Bang Liu*and Bin Fan*
*Key Laboratory of Agricultural Animal Genetics,Breeding &Reproduction of Ministry of Education,College of Animal Science &
Technology,Huazhong Agricultural University,Wuhan 430070,China.?The Key Laboratory for Domestic Animal Genetic Resources and Breeding of Ministry of Agriculture of China,Institute of Animal Science,Chinese Academy of Agricultural Sciences,Beijing 100193,China.?
Department of Animal Science and Center for Integrated Animal Genomics,Iowa State University,Ames,IA 50011,USA.
Summary
Due to the direction,intensity,duration and consistency of genetic selection,especially recent arti?cial selection,the production performance of domestic pigs has been greatly changed.Therefore,we reasoned that there must be footprints or selection signatures that had been left during domestication.In this study,with porcine 60K BeadChip genotyping data from both commercial Large White and local Chinese Tongcheng pigs,we calculated the extended haplotype homozygosity values of the two breeds using the long-range haplotype method to detect selection signatures.We found 34candidate regions,including 61known genes,from Large White pigs and 25regions comprising 57known genes from Tongcheng pigs.Many selection signatures were found on SSC1,SSC4,SSC7and SSC14regions in both populations.According to quantitative trait loci and network pathway analyses,most of the regions and genes were linked to growth,reproduction and immune responses.In addition,the average genetic differentiation coef?cient F ST was 0.254,which means that there had already been a signi?cant differentiation between the breeds.The ?ndings from this study can contribute to further research on molecular mechanisms of pig evolution and domestication and also provide valuable references for improvement of their breeding and cultivation.
Keywords extended haplotype homozygosity,genetic differentiation,long-range haplo-type,pig,selective sweep
Introduction
Domestic pigs evolved from the Eurasian wild boar and have a history of >9000years (Giuffra et al.2000).Since being subjected to both natural and arti?cial selection,especially strong and directional positive selection recently,the evolu-tionary direction of the pig has been more in line with the needs of humans.Hence,a number of breeds with distinct appearances and attributes have been https://www.doczj.com/doc/6f12545090.html,pared with the wild boar,domestic pigs have obvious differences not only in external characteristics but also in production performance:faster growth,higher reproductive capacity,more moderate temperament,etc.Even among domestic
pigs,there are various classi?cation types according to the use of the pig,such as lean pigs,fat pigs and even pet pigs.At the molecular level,once a population is selected,discrete mutations will be ?xed,the heterozygosity of the selected locus and the regions in the vicinity (a ‘selective sweep’)will be reduced and linkage disequilibrium (LD)regions will be extended (Vitti et al.2012).Recombination rate changes and inversions of chromosome separation can promote local LD with neighbouring loci (Ayala et al.2010;Nosil &Feder 2011).Furthermore,if these events continue in different directions for many of the loci undergoing strong selection,genetic drift could result at the selection sites and there could be longer regions with signi?cant LD (Slatkin 1975).The molecular population genetic theory of evolution posits that,when an advantageous mutation occurs in a population,it will be ?xed after several generations and allele frequency will increase in the population.In livestock breeds,because of the different mutation locations and frequencies,this can create different LD lengths and leave selective footprints or signatures,
Address for correspondence
B.Fan,Key Laboratory of Agricultural Animal Genetics,Breeding &Reproduction of Ministry of Education,College of Animal Science &Technology,Huazhong Agricultural University,Wuhan 430070,China.E-mail:fanbin@https://www.doczj.com/doc/6f12545090.html,
Accepted for publication 10December 2013
doi:10.1111/age.12128
329
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which have been used for studying the population’s evolution and differentiation.
Identi?cation of the genomic regions being targeted for selection in domestic animals is a hot area of research.However,until now there have been relatively few genomic regions with positive selection identi?ed.In recent years,with the emergence and utilisation of major livestock SNP chips,it has been possible to explore domestication and genetic differentiation at the genome-wide level.Based on the 60K porcine BeadChip genotyping data of both commercial Large White and local Chinese Tongcheng pigs,we attempted to use the long-range haplotype method to detect selection signals in these two populations and then calculated the genetic differentiation coef?cient F ST values for the candidate areas to analyse the extent of their genetic differentiation.We also tried to detect the potential selective sweeps in their evolution,which would contribute to better understanding of the molecular mechanisms of evolution and domestication in the pig.
Materials and methods Materials and quality control
DNA was extracted from Large White (n =408)and local Chinese Tongcheng pigs (n =45),which were sampled from a commercial pig farm and a Tongcheng pig conservation farm in Hubei Province respectively.Illumina porcine 60K BeadChip genotyping was performed commercially (Emei Tongde Technology Development Co.Ltd.)to obtain the SNP data.PLINK v.1.07software (Purcell et al.2007)was used to ?lter raw genotype data with the command:–maf 0.01–geno 0.1–mind 0.1–hwe 0.000001.Haplotypes were inferred with FASTPHASE v.1.2(Scheet &Stephens 2006),which uses a hidden Markov model of local haplotype assignment along each chromosome,allowing for either a block-like or gradual LD structure.To calculate the degree of genetic differentiation of the two populations,quality control standards were used as above.A total of 35235SNPs were analysed.
To visualise genetic distances between the two popula-tions,principal component analyses (PCAs)were obtained with GCTA v.1.20software (Yang et al.2011),which estimates the genetic relationship matrix between pairs of individuals from autosomal SNPs.PCA was run by pruning markers in high LD using the option –indep in PLINK .
The long-range haplotype test
To further investigate an unusual shared haplotype struc-ture and potential signatures of selection,Sabeti et al.(2002)assessed the deletion haplotype for evidence of extended homozygosity.Extended haplotype homozygosity (EHH)is de?ned as the probability that two randomly chosen chromosomes carrying the core haplotype of interest
are identical by descent (as assayed by homozygosity at all SNPs)for the entire interval from the core region to a distance x.EHH thus detects the transmission of an extend haplotype without recombination.The EHH of a tested core haplotype t is calculated as:
EHH t ?P s i ?1e ti 2 C t 2 where c is the number of samples of a particular haplotype,e is the number of samples of a particular extended haplotype and s is the number of unique extended haplotypes.
To correct for local variation in recombination rates,we compared the EHH of a tested core haplotype to that of other core haplotypes present at the locus,using a relative EHH (REHH)measurement.REHH is the ratio of the EHH of the tested haplotype with EHH ,which represents the mean decay of EHH for all other haplotypes.EHH is calculated as follows:
EHH ?P n j ?1;j ?t P s i ?1e i
2
P n i ?1;i ?t C i 2 where n is the number of different haplotypes.We chose
marker H for matching distances.This value is the degree to which each added marker at a further distance causes the extended haplotypes to decay for all core haplotypes and can be calculated as ‘all EHH’.A marker H of 0.04is roughly equal to a genetic distance of 0.25cm.Generally,the LD of commercial pigs is much larger than that of local pig breeds (Nsengimana et al.2004;Amaral et al.2008);therefore,we selected H =0.1for Large White and H =0.04for Tongcheng pigs.EHH and REHH values were calculated using SWEEP v.1.0(https://www.doczj.com/doc/6f12545090.html,/mpg/sweep/)software.
Estimates of F ST
The inbreeding coef?cient F ST is commonly used as a measure of the differentiation of allele frequencies between different populations.It can be interpreted as the probability that two alleles are identical by descent.To test whether F ST differed between the two populations,we used the population genetics software package,GENEPOP v.4.1.3(Rousset 2008).The de?nition of F ST used here is
F ST ?
MSP àMSI
MSP ten c à1TMSI tn c MSG
where MSG ,MSI and MSP represent the mean sums of squares for gametes,individuals and populations respec-tively,computed by an analysis of variance,and n c =(S 1–S 2/S 1)/(n –1),where S 1is the total sample size,
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S2is the sum of squares group sizes and n is the number of non-empty groups.
Individual SNP F ST values were smoothed over each chromosome using a local variable bandwidth kernel estimator(Herrmann1997),and we determined the smooth F ST using the R package‘lokern’(https://www.doczj.com/doc/6f12545090.html,/ web/packages/lokern/index.html).The qualitative guide-lines for interpreting F ST were as follows:the range0–0.05 indicates little genetic differentiation,the range0.05–0.15 indicates moderate genetic differentiation,the range 0.15–0.25indicates great genetic differentiation and values of F ST above0.25indicate very great genetic differentiation.
SNP annotation and QTL traits
SNP markers in the selected candidate regions were annotated.The reference genome Sus scrofa Build9was annotated using the Ensembl Genome Browser Database (https://www.doczj.com/doc/6f12545090.html,/index.html)and the NCBI database (https://www.doczj.com/doc/6f12545090.html,).We searched for gene regions where these SNPs were located.If the name of the candidate gene was ambiguous in both databases,we chose the Ensembl Genome Browser annotated name.
Utilising the pig QTL database(http://cn.animalgenome. org/cgi-bin/QTLdb/SS/index),we selected the major QTL traits or traits for which the peak values of QTL linkage regions were located in or nearest to the candidate regions.
Network analysis of the selected genes
Using INGENUITY PATHWAY ANALYSIS(IPA)v.7.0(http:// https://www.doczj.com/doc/6f12545090.html,)online tools,we analysed the biolog-ical network pathways of candidate genes.IPA was used to organise genes showing evidence of selection into networks of interacting genes and to identify pathways containing functionally related genes.Additionally,network analysis consisted of searching for direct and indirect interactions between candidate genes and other molecules(e.g.gene products or small molecules).Each of the network diagram genes or molecules contains more than one centre,and close contact with the centre genes or molecules is presented.Each gene is shown as a shape,and different shapes represent different gene functions.
Results
SNP genotyping analysis
A total of46359SNPs were found using quality control standards in Large White,and four individuals were removed because of a low genotyping rate[missingness per individual(MIND)>0.1].The genotyping rate in the remaining individuals was0.988;588SNPs failed the missingness test[missingness per marker(GENO)>0.1], 6816SNPs failed the allele frequency test(MAF<0.01),and359markers were excluded based on the Hardy Weinberg equilibrium(HWE)test.After frequency and genotyping pruning,there were39136SNPs chosen for further analysis.
Similarly,53781SNPs of Tongcheng pigs were subjected to quality control.Ultimately,one animal was removed for low genotyping(MIND>0.1)and34markers were excluded based on the HWE test.The genotyping rate for the remaining individuals was0.957;3148SNPs failed the missingness test(GENO>0.1)and23485SNPs failed the frequency test(MAF<0.01).After frequency and genotyp-ing pruning,29323SNPs remained.
Selective sweeps mapping
We analysed the population structure of Large White and Tongcheng pigs using PCA.The analysis clearly discrimi-nated Tongcheng from Large White pigs on the?rst three PC axes(Fig.S1).
We performed both REHH and F ST tests of neutrality on the full set of samples to identify regions that may have been targets of recent selective sweeps within and between populations.We measured REHH values at an H marker of 0.04for Large White and H marker of0.1for Tongcheng and obtained21424and19302cores respectively (Fig.1a).In Large White,there were more cores on SSC1, SSC4,SSC7,SSC13and SSC14,which contained43%of the total cores.SSC7and SSC14had the most cores,comprising up to10%of the total.However,in Tongcheng pigs,SSC1 had the most cores,accounting for11%,and was followed by SSC7,SSC4and SSC6,which accounted for8%,7%and 7%respectively.Again,SSC9,SSC13,SSC14and SSC15 accounted for6%.These chromosomes contain57%of all cores.
The average haplotype frequency for Large White was 0.23and for Tongcheng was0.22.We chose core haplo-types with a frequency>0.25and a REHH P-value<0.01 (log REHH P-value>2),and using these values,34cores and25cores were detected in Large White and Tongcheng respectively(Fig.1b).
Annotation of candidate regions
Annotating34candidate regions of the Large White pig,we found that these contained61known genes distributed on 15chromosomes(Tables1and2),whereas there were25 candidate containing57known genes on12chromosomes in Tongcheng pigs(Tables3and4).
From Tables1and2,the selected regions of the Large White were mostly on SSC1,SSC7,SSC13and SSC14, whereas there was no selection signatures on SSC3,SSC8, SSC9or https://www.doczj.com/doc/6f12545090.html,paring these candidate regions with pig QTL databases,they were closely linked to important economic QTL traits,including body weight,backfat thick-ness,average daily weight gain and lean meat content.
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As seen in Table 1,17regions consisting of 38genes were signi?cantly differentiated in Tongcheng pigs;these highly differentiated regions were linked to backfat,average daily lean meat gain,average chain length,average backfat thickness,subjective abnormal odour,adipocyte diameter,
belly weight,cooking loss,estimated carcass lean content and meat quality (yellowness)traits.However,as seen in Table 2,a total of 17candidate regions containing 24known genes were selected,and these areas did not show a very great signi?cant differentiation (F ST <0.25)in
Ton-
Figure 1Distribution of core haplotypes.
1a:Distribution of the core haplotypes on each chromosome of the two population genomes.Black and grey represent the Large White (LW)and Tongcheng (TC)respectively.1b:Distribution of LogREHH P -value vs.haplotype frequencies in the LW and TC genomes respectively.The vertical dashed line =0.25,and the horizontal dashed line =2.LogREHH was calculated at H =0.04(approximately 0.25cm)distances in the upstream and downstream direction for all possible core haplotypes in TC pigs,and LW was calculated using H =0.1.REHH,relative extended haplotype homozygosity.
Table 1Selected and signi?cantly different regions (F ST ≥0.25)with Tongcheng regions and related genes in Large White.Chr Position (Mbp)Genes
Haplotype frequency REHH P-value Average F ST QTL traits 277.17–77.35JMY,HOMER10.280.00750.29Backfat
4123.78–123.9–
0.520.00220.36Body weight 58.47–8.54RBFOX2
0.310.00620.3–6
117.36–118.15
TAL1,CYP4A21,CYP4B1,SNORA73,KIAA0494,ATPAF1,MOB3C,MKNK1,KNCN,DMBX1,FAAH 0.26
0.002
0.27
–
720.695–20.77FAM65B
0.2760.00130.34Backfat 7120.89–121.23CCDC88C,SMEK1,CATSPERB
0.350.00910.29Backfat 7131.27–131.75TECPR2,RPS21,MOK,ZNF839,WDR20,HSP90AA10.328.6E-040.28–
1020.60–20.64KCNT2
0.4890.00410.35Body weight (birth)129.96–10.00WIPI1,ARSG
0.280.00430.3Average chain length
1319.27–19.69SCN5A,SCN10A,WDR480.260.0060.41Average backfat thickness 1324.19–24.26LARS20.260.00170.29–
1438.16–38.46TBX5
0.310.00390.4Subjective abnormal odour 1478.40–78.60DNAJB12,MICU10.357.9E-040.27Adipocyte diameter 14146.34–146.38GLRX30.320.00390.41Belly weight 16 3.22–3.29FAM105A 0.260.00920.54Cooking loss
16 5.71–5.99MYO100.36 2.5E-040.33Estimated carcass lean content 17
53.05–53.11
CSE1L
0.37
0.0071
0.29
CIE-b
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Table2Selected regions that are not greatly signi?cant(F ST<0.25)from Tongcheng regions and related genes in Large White.
Chr Position(Mbp)Genes Haplotype
frequency REHH P-value Average F ST QTL traits
115.85–15.94ESR1,C6orf970.560.00920.15–
116.06–16.16AKAP120.320.00960.14–
126.99–27.03CCDC28A0.280.00360.12Average daily gain
241.07–41.13INSC0.40.00960.003Average daily gain
2120.08–120.17ADAMTS190.260.00780.15Average daily gain
4115.71–115.76AKNAD1,STXBP30.280.00910.09Body weight
7135.82–135.95GSTA4,ICK0.3780.00860.2–
7126.97–127.03VRK1,BCL11B0.2850.00790.08Average daily gain
1176.41–76.46MYO160.330.00210.15Muscle fat content
1210.85–10.97PRKCA0.3080.00570.16Body weight(birth) 1224.68–24.73PPP1R9B,ITGA3,COL1A10.270.00790.06Ear area
13141.38–141.56DSCR30.3030.00530.08Body weight(birth)
147.008–7.035PEBP4,EGR30.45 1.40E-040.06–
14130.47–130.52VWA2,AFAP1L20.310.00110.12Subjective lean boar?avour 1727.37–27.42–0.360.00880.24Shoulder external fat weight 1836.74–36.81AOAH0.630.00710.18Backfat
X106.51–106.70–0.3550.00990.07–
Table3Selected regions that are greatly signi?cantly different(F ST≥0.25)from Large White regions and related genes in Tongcheng.
Chr Position(Mbp)Genes Haplotype
frequency REHH P-value Average F ST QTL traits
1195.15–195.58EXOC5,C14orf105,SLC35F40.500.00050.28Abdominal fat weight 28.04–8.16MYRF,DAGLA0.420.00140.65–
487.70–88.87FAM78B,TMCO1,ALDH9A1,MGST30.250.00330.26Average daily gain
557.50–57.59LRP60.440.0090.26Backfat
559.21–59.39PHC10.400.00370.31
7103.82–104.09DPF30.270.00680.25Backfat
10 6.8–7.03ESRRG0.50.00920.38Body depth
1046.65–46.86PDSS10.250.00030.38Subjective abnormal odour 15126.71–127.05UGT1A1,HJURP,TRPM80.380.00920.35Meat colour
1726.64–26.87BANF20.410.00890.29Ear weight
1758.07–58.11DOK50.310.00550.36Fat-cuts percentage
X33.86–34.64–0.290.00430.38Average daily gain Table4Selected regions that are not greatly signi?cantly differentiated(F ST<0.25)from Large white regions and related genes in Tongcheng.
Chr Position(Mbp)Genes Haplotype
frequency REHH P-value Average F ST QTL traits
1266.31–266.39SNX30,SLC46A20.470.00240.23Backfat
1267.84–267.97COL27A1,KIF120.450.0077–
2 6.47–7.00OTUB1,COX8A,C11orf84,RCOR2,
MARK2,RPL22,RTN3,ATL3,LGALS12
0.370.00090.08–
2129.82–129.92PCDHB5,PCDHGC50.260.00590.22Abdominal fat weight
495.18–95.42SPTA10.740.00780.14Average daily gain
620.7–20.92SLC6A2,LPCAT2,MMP20.320.00250.17Backfat
7135.84–135.87ICK0.660.00570.16–
887.18–87.22ADAD1,KIAA1109,IL21,IL20.650.00890.12Total body fat tissue
linear
1439.47–40.08C12orf51,TRAFD1,NAA25,ERP29,U6,
ALDH2,MAPKAPK5,TMEM116
0.340.00740.1Fat androstenone level
14119.47–119.6CALHM2,CALHM1,CALHM3,NEURL0.520.00140.19Body weight
14143.66–143.73FAM196A0.260.00870.2Belly weight
14144.11–144.33–0.570.00950.1
1517.73–19.98LYPD10.450.00440.22Chew score
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gcheng pigs;these traits included mainly average daily gain,birth weight and muscle fat content.
In Tongcheng pigs,only 12chromosomes contained detected signatures,and SSC1and SSC14had the most signals,but there were no signals on SSC3,SSC9,SSC11,SSC12,SSC13,SSC16or SSC18.Similarly,when compared with QTL databases,these selected regions were involved mainly in major economic traits (e.g.back fat,abdominal fat deposition,average daily gain,body depth)and other traits (e.g.body odour,ear area).At the same time,we detected 12signi?cantly different selected regions contain-ing 19genes when compared with the Large White;these might be signi?cant differentiation traits,such as abdominal fat weight,backfat thickness,body depth,average daily gain and ear area (Table 3).As seen in Table 4,13selected regions consisting of 38genes were not highly differentiated from Large White,and these corresponding traits included backfat thickness,abdominal fat weight,average daily gain,belly meat content,fat androstenone level,body weight,belly weight and chew score.
Distribution of F ST among SNPs and populations
A total of 35235SNPs were used to calculate F ST values,and 32742F ST values were obtained (Fig.2).In addition,as originally de?ned,F ST ranged from 0to 1.However,the above unbiased method for estimating F ST could produce negative values.This observation,which had no biological interpretation,simply re?ected the consequences of sam-pling error when the population subdivision is weak.In this study,the average genetic differentiation coef?cient F ST was 0.254,indicating that the two populations were highly differentiated.
Different genetic backgrounds and living environments,as well as different selection intensity and direction,could
cause the great differences in appearance and reproductive performance seen in these populations.As shown in Fig.3,four chromosomes (SSC9,SSC10,SSC12and SSC18)had a gentler F ST change,and this differentiation was not extremely signi?cant.However,SSC11and SSC14showed more intense changes,and most of the regions had a high degree of differentiation.
Network analyses of genes under selection
Referencing the human and mouse genomes,we analysed the network pathway of selected candidate genes of the Large White pigs,and 59candidate genes were mapped,but two genes (CYP4A21and SNORA73)were not (Fig.4).The selected genes mostly centred around the ESR1,NF-kB,IL1,LH and insulin genes.Similarly,by analysing the pathway of 57candidate genes of Tongcheng pigs,56genes were mapped,but the U6gene was not.After removing 20genes that were associated only with UBC (Fig.5),these genes were mainly centred around insulin,immunoglobulin and ERK1/2genes.To analyse signi?cantly different genes in the two populations,we produced a network pathway diagram of 57signi?cant differentiation genes;CYP4A21and SNORA73were not mapped.Deleting 15candidates that were related only to the UBC gene,genes encoding for NF-kB,Ca 2+and tretinoin were found near these highly differentiated genes (Fig.6).
Discussion
Ef?cient arti?cial selection has a dramatic in?uence on livestock genome diversity and LD.This effect depends on the direction,intensity,duration and consistency of selec-tion over time (Du et al.2007).For a long time,selection in the pig has focused on growth and body mass to meet the demands of humans.The availability of dense marker panels provides the opportunity to determine the LD between regions and to search for selection signatures as a means of identifying causative mutations or other useful markers,as has been done in several species.In the analysed populations,a number of widespread signals of positive selection were found,and these might be associated with signi?cant phenotypic variations.
In Large White pigs,we detected 34strong positive selection regions consisting of 61candidate genes,and most of them were associated with growth,reproduction and disease resistance.There were more signals on SSC7and SSC14,suggesting that they play more critical roles during the selection procedure.As shown in Fig.4,we found several central genes and nuclear factors.Estrogen receptor 1(encoded by ESR1)is an activating transcription factor that controls speci?c original hormone-responsive DNA elements (oestrogen response elements).It exists in a wide variety of animals and is involved in the expression and regulation of the genes of female gonadal tissue;it also can
Figure 2The number and distribution of SNP F ST across both populations.
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improve reproduction and production traits of pigs(Short et al.1997).The ESR1polymorphism was linked with teat number and litter size of the pig(Rothschild et al.1996). Nuclear factor kappa-light-chain enhancer of activated B cells(NF-kB)is a transcription factor regulating the innate and adaptive immune response(Hoffmann&Baltimore 2006).It can traf?c into the nucleus by cascade phosphor-ylation and then up-regulate gene expression(Gilmore 2006).Interleukin-1(IL-1)is produced mainly by activated monocytes–macrophages and can promote B-cell prolifera-tion and antibody secretion,thus enhancing the body’s resistance to disease(van Asseldonk et al.2010).Luteinis-ing hormone(LH)is a hormone produced by gonadotroph cells in the anterior pituitary gland and acts synergistically with follicle-stimulating hormone(FSH)to promote oocyte maturation in pigs(Mattioli et al.1991).Insulin is a peptide hormone produced by B cells of the pancreas that is central to regulating carbohydrate and fat metabolism in the body. Insulin-like growth factors play an important role in the growth and development of the pig and lead to increased backfat thickness and lean meat content(Vykoukalova et al. 2006;Pierzchala et al.2012).
In Tongcheng pigs,we detected25selection signatures, including57candidate genes corresponding to QTL regions for traits of economic importance(e.g.backfat thickness, abdominal fat deposition,average daily weight gain,body depth,?esh colour)and other traits(e.g.subjective abnor-mal odour,ear area).Most of the genes centred around immunoglobulin.Ig is a class of glycoproteins,generated by plasma cells,that recognise antigens and in?uence
the
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proliferation and differentiation of B cells.It is present mainly in serum and other body ?uids,speci?cally binds to its corresponding antigens and has immune function,so it is also an important immune molecule mediating humoral immunity (Litman et al.1993;Butler 1997).
It is worth noting that ESR1was one of the candidate genes selected in Large White,and considered to be a candidate gene for reproduction.Oestrogen is known for its role in the development and functioning of the female reproductive system.The primary mechanism of oestrogen’s action is via binding and modulation of activity of the estrogen receptors (coded by ESR1and ESR2),which are ligand-dependent nuclear transcription factors expressed at high levels in female tissues critical to reproduction,including the ovaries,uterus,cervix,mammary glands and pituitary gland (Kowalski et al.2004;Munoz et al.2004).In pigs,ESR1is located on chromosome 1and has a crucial role in the female biology of reproduction,which justi?es further research on the association of other SNPs with litter size,and ESR1mRNA levels showed maximal expression at early pregnancy (Rothschild et al.1996).In addition,several genes (MICU1,GLRX3,CCDC170,LARS2,GSTA1)related to HNF4A were detected in Large White pigs.Hepatocyte nuclear factors (HNFs)are a group of phylogenetically unrelated transcription factors that regu-late the transcription of a diverse group of genes into proteins.These proteins include blood clotting factors and enzymes and transporters involved in glucose,cholesterol and fatty acid transport and metabolism (Costa et al.2003).HNF4A mainly regulates fatty acid,cholesterol and lipopro-tein metabolism in the liver (Chamouton &Latruffe 2012).Similar to for Large White pig,?ve genes (UGT1A1,GPR39,KIF12,C14orf105and COL27A1)directly associated with HNF1A that have been demonstrated to be associated with pig fatness and loin muscle were found (Fan et al.2010).The results of this study showed that the growth and reproduction traits of the two populations had experienced strong positive selection,and the Tongcheng pigs had more signatures relating to the immune response than did the Large White pigs.Additionally,the two groups showed few overlapping selection regions,and only the region from 135–136Mbp on SSC7,containing the ICK gene,showed selection for both populations.The intestinal cell (MAK-like)kinase (ICK )is expressed in lymphocytes and is involved in signal transduction pathways regulating the body’s resis-tance to diseases (Perlmutter et al.1988).
Because of the limit of statistical methods and selection criteria,several loci that had been proven to be selected,such as the MC1R gene,were not detected in our study.Coat colour and key pattern traits also have been selected in the development of livestock and companion animal breeds,as they were under selection well before breed development.A number of genes have been associated with coat colour in pigs,including the MC1R gene (Fang et al.2009).MC1R
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in?uences the relative levels of eumelanin(black/brown) and phaeomelanin(yellow/red)pigments and appears to have been a target for selection in pigs.The MC1R gene is located at0.256Mbp on SSC6in the pig,but in Sus Scrofa Build9,the?rst SNP markers of SSC6lay at1.06Mbp; thus,MC1R could not be detected at this time.
Because pig breeds from Asian and European populations were domesticated from different ancestors,they are expected to have distinct genetic diversities.The Large White is one of the most numerous of all pig breeds and is widely used in crossbreeding for intensive pig farming around the world.The Large White displays greater fecundity,larger feed conversion ratio and slaughter rate and greater adaptability.The Tongcheng pig is short and wide with medium ears and abdominal fullness and has high fat,thin bone and highly lean and tender meat.As shown in Fig.3,we found that there was an apparent peak between50and60Mbp of SSC4,which is involved in average daily weight gain(Walling et al.1998).Addition-ally,there was a peak at35to40Mbp on SSC11,and this region may be associated with the ear area(Ma et al.2009). Tretinoin,one of the centred molecules,is the acid form of a vitamin that can reduce epidermal cell condensation,accelerate the metabolism of the epidermis and improve skin(Weiss et al.1988).Additionally,six genes(KIAA0494, RBFOX2,WIPI1,FAM105A,PHC1and TMCO1)were directly related to the RNA-binding protein embryonic lethal abnormal vision(ELAVL1),which is regulated by heat-shock protein HSPA2/HSP70-2,a crucial regulator of spermatogenesis,and plays a dominant role in placental labyrinth morphogenesis,skeletal speci?cation patterns and splenic ontogeny(Katsanou et al.2009;Chi et al.2011). Detection of selection signatures is an important and challenging area of research.The current study,however, detected only a minority of regions or genes,and most of the selective sweeps have not been detected.New statistical tests,such as the site frequency spectrum(Nielsen et al. 2005),goodness of?t(Jensen et al.2005)and composite of multiple signals(Grossman et al.2010),have been devel-oped in the past few years.These enable us to infer evidence of recent strong positive selection from genome-wide data and to localise the targets of selection.
Although the proposed selective sweeps theory provides a theoretical basis to explore the evolution and differentiation of populations,and the porcine SNP chip promotes researching genetic evolution at the molecular level
candidate genes
dashed
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Selection signatures in pigs337
between and within populations,it is still limited in detecting select sweeps at the pig genome level for several reasons:(i)European pigs’LD is much longer than that of the local Chinese pigs,but the current SNP chip is based mainly on European pigs,so the current SNP chips do not contain all of the information for the pigs or most of the information for local pig breeds;(ii)the updated pig genome annotation is in progress,and there might be inexact information for selected regions;and (iii)the local pig population size is limited.Therefore,more effort towards both experimental and statistical approaches is needed.
Acknowledgements
This study was supported by the National Science Founda-tion of China (31072009,31172192),New Century Excellent Talents (NCET-11-0646)and Fundamental Research Funds for the Central Universities (2012PY009).
References
Amaral A.J.,Megens H.J.,Crooijmans R.P.,Heuven H.C.&Groenen M.A.(2008)Linkage disequilibrium decay and haplotype block structure in the pig.Genetics 179,569–79.
van Asseldonk E.J.P.,Stienstra R.,Koenen T.B.,van Tits L.J.H.,Joosten L.A.B.,Tack C.J.&Netea M.G.(2010)The effect of the Interleukin-1cytokine family members IL-1F6and IL-1F8on adipocyte differentiation.Obesity 18,2234–6.
Ayala D.,Fontaine M.C.,Cohuet A.,Fontenille D.,Vitalis R.&Simard F.(2010)Chromosomal inversions,natural selection and adaptation in the malaria vector anopheles funestus .Molecular Biology and Evolution 28,745–58.
Butler J.E.(1997)Immunoglobulin gene organization and the mechanism of repertoire development.Scandinavian Journal of Immunology 45,455–62.
Chamouton J.&Latruffe N.(2012)PPARalpha/HNF4alpha inter-play on diversi?ed responsive elements.Relevance in the regu-lation of liver peroxisomal fatty acid catabolism.Current Drug Metabolism 13,1436–53.
Chi M.N.,Auriol J.,Jegou B.,Kontoyiannis D.L.,Turner J.M.,de Rooij D.G.&Morello D.(2011)The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis,acting both at meiotic and postmeiotic stages.Molecular Biology of the Cell 22,2875–85.
Costa R.H.,Kalinichenko V.V.,Holterman A.X.&Wang X.(2003)Transcription factors in liver development,differentiation,and regeneration.Hepatology 38,1331–47.
Du F.X.,Clutter A.C.&Lohuis M.M.(2007)Characterizing linkage disequilibrium in pig populations.International Journal of Biolog-ical Sciences 3,166–78.
Fan B.,Du Z.Q.&Rothschild M.F.(2010)The hepatocyte nuclear factor-1alpha (HNF1A )gene is associated with fatness and loin muscle area in the pig.Animal 4,1619–27.
Fang M.,Larson G.,Ribeiro H.S.,Li N.&Andersson L.(2009)Contrasting mode of evolution at a coat color locus in wild and domestic pigs.PLoS Genetics 5,16.
Gilmore T.D.(2006)Introduction to NF-j B:players,pathways,perspectives.Oncogene 25,6680– 4.
Tongcheng.Symbols products ?2014Stichting International Foundation for Animal Genetics,45,329–339
Li et al.
338
Giuffra E.,Kijas J.M.,Amarger V.,Carlborg O.,Jeon J.T.& Andersson L.(2000)The origin of the domestic pig:independent domestication and subsequent introgression.Genetics154, 1785–91.
Grossman,S.R.,Shlyakhter,I.,Karlsson, E.K.,et al.(2010)A composite of multiple signals distinguishes causal variants in regions of positive selection,Science,327,883–6.
Herrmann E.(1997)Local bandwidth choice in kernel regression estimation.Journal of Computational and Graphical Statistics6, 35–54.
Hoffmann A.&Baltimore D.(2006)Circuitry of nuclear factor kB. Immunological Reviews210,171–86.
Jensen J.D.,Kim Y.,DuMont V.B.,Aquadro C.F.&Bustamante C.D. (2005)Distinguishing between selective sweeps and demography using DNA polymorphism data.Genetics170,1401–10. Katsanou V.,Milatos S.,Yiakouvaki A.,Sgantzis N.,Kotsoni A., Alexiou M.,Harokopos V.,Aidinis V.,Hemberger M.&Kontoy-iannis D.L.(2009)The RNA-binding protein Elavl1/HuR is essential for placental branching morphogenesis and embryonic development.Molecular and Cellular Biology29,2762–76. Kowalski A.A.,Vale-Cruz D.S.,Simmen F.A.&Simmen R.C.(2004) Uterine androgen receptors:roles in estrogen-mediated gene expression and DNA synthesis.Biology of Reproduction70,1349–57. Litman G.W.,Rast J.P.,Shamblott M.J.,Haire R.N.,Hulst M.,Roess W.,Litman R.T.,Hinds-Frey K.R.,Zilch A.&Amemiya C.T. (1993)Phylogenetic diversi?cation of immunoglobulin genes and the antibody repertoire.Molecular Biology and Evolution10, 60–72.
Ma J.,Qi W.,Ren D.et al.(2009)A genome scan for quantitative trait loci affecting three ear traits in a White Duroc9Chinese Erhualian resource population.Animal Genetics40,463–7. Mattioli M.,Bacci M.L.,Galeati G.&Seren E.(1991)Effects of LH and FSH on the maturation of pig oocytes in vitro.Theriogenology 36,95–105.
Munoz G.,Ovilo C.,Amills M.&Rodriguez C.(2004)Mapping of the porcine oestrogen receptor2gene and association study with litter size in Iberian pigs.Animal Genetics35,242–4.
Nielsen R.,Williamson S.,Kim Y.,Hubisz M.J.,Clark A.G.& Bustamante C.(2005)Genomic scans for selective sweeps using SNP data.Genome Research15,1566–75.
Nosil P.&Feder J.L.(2011)Genomic divergence during speciation: causes and consequences.Philosophical Transactions of the Royal Society B:Biological Sciences367,332–42.
Nsengimana J.,Baret P.,Haley C.S.&Visscher P.M.(2004)Linkage disequilibrium in the domesticated pig.Genetics166,1395–404. Perlmutter R.M.,Marth J.D.,Lewis D.B.,Peet R.,Ziegler S.F.&Wilson C.B.(1988)Structure and expression of Ick transcripts in human lymphoid cells.Journal of Cellular Biochemistry38,117–26. Pierzchala M.,Pareek C.S.,Urbanski P.,Goluch D.,Kamyczek M., Rozycki M.,Smoczynski R.,Horbanczuk J.O.&Kuryl J.(2012) Study of the differential transcription in liver of growth hormone receptor(GHR),insulin-like growth factors(IGF1,IGF2)and
insulin-like growth factor receptor(IGF1R)genes at different postnatal developmental ages in pig breeds.Molecular Biology Reports39,3055–66.
Purcell S.,Neale B.,Todd-Brown K.et al.(2007)PLINK:a tool set for whole-genome association and population-based linkage analy-ses.The American Journal of Human Genetics81,559–75. Rothschild M.,Jacobson C.,Vaske D.et al.(1996)The estrogen receptor locus is associated with a major gene in?uencing litter size in pigs.Proceedings of the National Academy of Sciences of the United States of America93,201–5.
Rousset F.(2008)GENEPOP’007:a complete re-implementation of the GENEPOP software for Windows and Linux.Molecular Ecology Resources8,103–6.
Sabeti P.C.,Reich D.E.,Higgins J.M.et al.(2002)Detecting recent positive selection in the human genome from haplotype struc-ture.Nature419,832–7.
Scheet P.&Stephens M.(2006)A fast and?exible statistical model for large-scale population genotype data:applications to inferring missing genotypes and haplotypic phase.The American Journal of Human Genetics78,629–44.
Short T.H.,Rothschild M.F.,Southwood O.I.et al.(1997)Effect of the estrogen receptor locus on reproduction and production traits in four commercial pig lines.Journal of Animal Science75,3138–42.
Slatkin M.(1975)Gene?ow and selection in a two-locus system. Genetics81,787–802.
Vitti J.J.,Cho M.K.,Tishkoff S.A.&Sabeti P.C.(2012)Human evolutionary genomics:ethical and interpretive issues.Trends in Genetics28,137–45.
Vykoukalova Z.,Knoll A.,Dvorak J.&Cepica S.(2006)New SNPs in the IGF2gene and association between this gene and backfat thickness and lean meat content in Large White pigs.Journal of Animal Breeding and Genetics123,204–7.
Walling G.A.,Archibald A.L.,Cattermole J.A.,Downing A.C., Finlayson H.A.,Nicholson D.,Visscher P.M.,Walker C.A.& Haley C.S.(1998)Mapping of quantitative trait loci on porcine chromosome4.Animal Genetics29,415–24.
Weiss J.S.,Ellis C.N.,Headington J.T.,Tincoff T.,Hamilton T.A.& Voorhees J.J.(1988)Topical tretinoin improves photoaged skin.
A double-blind vehicle-controlled study.The Journal of the American Medical Association259,527–32.
Yang J.,Lee S.H.,Goddard M.E.&Visscher P.M.(2011)GCTA:a tool for genome-wide complex trait analysis.The American Journal of Human Genetics88,76–82.
Supporting information
Additional supporting information may be found in the online version of this article.
Figure S1Population structures of Large White and Tongcheng pigs.
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Deems Taylor: The Monster 怪才他身材矮小，头却很大，与他的身材很不相称——是个满脸病容的矮子。他神经兮兮，有皮肤病，贴身穿比丝绸粗糙一点的任何衣服都会使他痛苦不堪。而且他还是个夸大妄想狂。他是个极其自负的怪人。除非事情与自己有关，否则他从来不屑对世界或世人瞧上一眼。对他来说，他不仅是世界上最重要的人物，而且在他眼里，他是惟一活在世界上的人。他认为自己是世界上最伟大的戏剧家之一、最伟大的思想家之一、最伟大的作曲家之一。听听他的谈话，仿佛他就是集莎士比亚、贝多芬、柏拉图三人于一身。想要听到他的高论十分容易，他是世上最能使人筋疲力竭的健谈者之一。同他度过一个夜晚，就是听他一个人滔滔不绝地说上一晚。有时，他才华横溢；有时，他又令人极其厌烦。但无论是妙趣横生还是枯燥无味，他的谈话只有一个主题：他自己，他自己的所思所为。他狂妄地认为自己总是正确的。任何人在最无足轻重的问题上露出丝毫的异议，都会激得他的强烈谴责。他可能会一连好几个小时滔滔不绝，千方百计地证明自己如何如何正确。有了这种使人耗尽心力的雄辩本事，听者最后都被他弄得头昏脑涨，耳朵发聋，为了图个清静，只好同意他的说法。他从来不会觉得，对于跟他接触的人来说，他和他的所作所为并不是使人产生强烈兴趣而为之倾倒的事情。他几乎对世间的任何领域都有自己的理
论，包括素食主义、戏剧、政治以及音乐。为了证实这些理论，他写小册子、写信、写书……文字成千上万，连篇累牍。他不仅写了，还出版了这些东西——所需费用通常由别人支付——而他会坐下来大声读给朋友和家人听，一读就是好几个小时。他写歌剧，但往往是刚有个故事梗概，他就邀请——或者更确切说是召集——一群朋友到家里，高声念给大家听。不是为了获得批评，而是为了获得称赞。整部剧的歌词写好后，朋友们还得再去听他高声朗读全剧。然后他就拿去发表，有时几年后才为歌词谱曲。他也像作曲家一样弹钢琴，但要多糟有多糟。然而，他却要坐在钢琴前，面对包括他那个时代最杰出的钢琴家在内的聚会人群，一小时接一小时地给他们演奏，不用说，都是他自己的作品。他有一副作曲家的嗓子，但他会把著名的歌唱家请到自己家里，为他们演唱自己的作品，还要扮演剧中所有的角色。他的情绪犹如六岁儿童，极易波动。心情不好时，他要么用力跺脚，口出狂言，要么陷入极度的忧郁，阴沉地说要去东方当和尚，了此残生。十分钟后，假如有什么事情使他高兴了，他就会冲出门去，绕着花园跑个不停，或者在沙发上跳上跳下或拿大顶。他会因爱犬死了而极度悲痛，也会残忍无情到使罗马皇帝也不寒而栗。他几乎没有丝毫责任感。他似乎不仅没有养活自己的能力，也从没想到过有这个义务。他深信这个世界应该给他一条活路。为了支持这一信念，他
必修一阅读鉴赏第一单元1.*沁园春?长沙……………………………………毛泽东3 2.诗两首雨巷…………………………………………戴望舒6 再别康桥………………………………………徐志摩8 3.大堰河--我的保姆………………………………艾青10 第二单元4.烛之武退秦师………………………………….《左传》16 5.荆轲刺秦王………………………………….《战国策》18 6.*鸿门宴……………………………………..司马迁22 第三单元7.记念刘和珍君……………………………………鲁迅27 8.小狗包弟……………………………………….巴金32 9.*记梁任公先生的一次演讲…………………………梁实秋36 第四单元10.短新闻两篇别了，“不列颠尼亚”…………………………周婷杨兴39 奥斯维辛没有什么新闻…………………………罗森塔尔41 11.包身工………………………………………..夏衍44 12.*飞向太空的航程……………………….贾永曹智白瑞雪52 必修二阅读鉴赏第一单元1.荷塘月色…………………………………..朱自清2.故都的秋…………………………………..郁达夫3.*囚绿记…………………………………..陆蠡第二单元4.《诗经》两首氓采薇5.离骚………………………………………屈原6.*《孔雀东南飞》(并序) 7.*诗三首涉江采芙蓉《古诗十九首》短歌行……………………………………曹操归园田居(其一)…………………………..陶渊明第三单元8.兰亭集序……………………………………王羲之9.赤壁赋……………………………………..苏轼10.*游褒禅山记………………………………王安石第四单元11.就任北京大学校长之演说……………………..蔡元培12.我有一个梦想………………………………马丁?路德?金1 3.*在马克思墓前的讲话…………………………恩格斯第三册阅读鉴赏第一单元1.林黛玉进贾府………………………………….曹雪芹2.祝福………………………………………..鲁迅3. *老人与海…………………………………….海明威第二单元4.蜀道难……………………………………….李白5.杜甫诗三首秋兴八首(其一) 咏怀古迹(其三) 登高6.琵琶行(并序)………………………………..白居易7.*李商隐诗两首锦瑟马嵬(其二) 第三单元8.寡人之于国也…………………………………《孟子》9.劝学……………………………………….《荀子》10.*过秦论…………………………………….贾谊11.*师说………………………………………韩愈第四单元12.动物游戏之谜………………………………..周立明13.宇宙的边疆………………………………….卡尔?萨根14.*凤蝶外传……………………………………董纯才15.*一名物理学家的教育历程……………………….加来道雄第四册阅读鉴赏第一单元1.窦娥冤………………………………………..关汉卿2.雷雨………………………………………….曹禹3.*哈姆莱特……………………………………莎士比亚第二单元4.柳永词两首望海潮(东南形胜) 雨霖铃(寒蝉凄切) 5.苏轼词两首念奴娇?赤壁怀古定风波(莫听穿林打叶声) 6.辛弃疾词两首水龙吟?登建康赏心亭永遇乐?京口北固亭怀古7.*李清照词两首醉花阴(薄雾浓云愁永昼) 声声慢(寻寻觅觅) 第三单元8.拿来主义……………………………………….鲁迅9.父母与孩子之间的爱……………………………..弗罗姆10.*短文三篇热爱生
Frankenstein's Monster Part 1 The story of Frankenstein Frankenstein is a young scientist/ from Geneva, in Switzerland. While studying at university, he discovers the secret of how to give life/ to lifeless matter. Using bones from dead bodies, he creates a creature/ that resembles a human being/ and gives it life. The creature, which is unusually large/ and strong, is extremely ugly, and terrifies all those/ who see it. However, the monster, who has learnt to speak, is intelligent/ and has human emotions. Lonely and unhappy, he begins to hate his creator, Frankenstein. When Frankenstein refuses to create a wife/ for him, the monster murders Frankenstein's brother, his best friend Clerval, and finally, Frankenstein's wife Elizabeth. The scientist chases the creature/ to the Arctic/ in order to destroy him, but he dies there. At the end of the story, the monster disappears into the ice/ and snow/ to end his own life. Part 2 Extract from Frankenstein It was on a cold November night/ that I saw my creation/ for the first time. Feeling very anxious, I prepared the equipment/ that would give life/ to the thing/ that lay at my feet. It was already one/ in the morning/ and the rain/ fell against the window. My candle was almost burnt out when, by its tiny light，I saw the yellow eye of the creature open. It breathed hard, and moved its arms and legs. How can I describe my emotions/ when I saw this happen? How can I describe the monster who I had worked/ so hard/ to create? I had tried to make him beautiful. Beautiful! He was the ugliest thing/ I had ever seen! You could see the veins/ beneath his yellow skin. His hair was black/ and his teeth were white. But these things contrasted horribly with his yellow eyes, his wrinkled yellow skin and black lips. I had worked/ for nearly two years/ with one aim only, to give life to a lifeless body. For this/ I had not slept, I had destroyed my health. I had wanted it more than anything/ in the world. But now/ I had finished, the beauty of the dream vanished, and horror and disgust/ filled my heart. Now/ my only thoughts were, "I wish I had not created this creature, I wish I was on the other side of the world, I wish I could disappear!” When he turned to look at me, I felt unable to stay in the same room as him. I rushed out, and /for a long time/ I walked up and down my bedroom. At last/ I threw myself on the bed/ in my clothes, trying to find a few moments of sleep. But although I slept, I had terrible dreams. I dreamt I saw my fiancée/ walking in the streets of our town. She looked well/ and happy/ but as I kissed her lips，they became pale, as if she were dead. Her face changed and I thought/ I held the body of my dead mother/ in my arms. I woke, shaking with fear. At that same moment，I saw the creature/ that I had created. He was standing/by my bed/ and watching me. His
人教版高中语文必修必背课文精编W O R D版 IBM system office room 【A0816H-A0912AAAHH-GX8Q8-GNTHHJ8】
必修1 沁园春·长沙（全文）毛泽东 独立寒秋， 湘江北去， 橘子洲头。 看万山红遍， 层林尽染， 漫江碧透， 百舸争流。 鹰击长空， 鱼翔浅底， 万类霜天竞自由。 怅寥廓， 问苍茫大地， 谁主沉浮。 携来百侣曾游， 忆往昔峥嵘岁月稠。
恰同学少年， 风华正茂， 书生意气， 挥斥方遒。 指点江山， 激扬文字， 粪土当年万户侯。 曾记否， 到中流击水， 浪遏飞舟。 雨巷（全文）戴望舒撑着油纸伞，独自 彷徨在悠长、悠长 又寂寥的雨巷， 我希望逢着 一个丁香一样地
结着愁怨的姑娘。 她是有 丁香一样的颜色， 丁香一样的芬芳， 丁香一样的忧愁， 在雨中哀怨， 哀怨又彷徨； 她彷徨在这寂寥的雨巷，撑着油纸伞 像我一样， 像我一样地 默默彳亍着 冷漠、凄清，又惆怅。她默默地走近， 走近，又投出 太息一般的眼光
她飘过 像梦一般地， 像梦一般地凄婉迷茫。像梦中飘过 一枝丁香地， 我身旁飘过这个女郎；她默默地远了，远了，到了颓圮的篱墙， 走尽这雨巷。 在雨的哀曲里， 消了她的颜色， 散了她的芬芳， 消散了，甚至她的 太息般的眼光 丁香般的惆怅。 撑着油纸伞，独自
彷徨在悠长、悠长 又寂寥的雨巷， 我希望飘过 一个丁香一样地 结着愁怨的姑娘。 再别康桥（全文）徐志摩 轻轻的我走了，正如我轻轻的来； 我轻轻的招手，作别西天的云彩。 那河畔的金柳，是夕阳中的新娘； 波光里的艳影，在我的心头荡漾。 软泥上的青荇，油油的在水底招摇； 在康河的柔波里，我甘心做一条水草！ 那榆荫下的一潭，不是清泉， 是天上虹揉碎在浮藻间，沉淀着彩虹似的梦。寻梦？撑一支长篙，向青草更青处漫溯， 满载一船星辉，在星辉斑斓里放歌。
Unit 7 The Monster Deems Taylor 1He was an undersized little man, with a head too big for his body ― a sickly little man. His nerves were bad. He had skin trouble. It was agony for him to wear anything next to his skin coarser than silk. And he had delusions of grandeur. 2He was a monster of conceit. Never for one minute did he look at the world or at people, except in relation to himself. He believed himself to be one of the greatest dramatists in the world, one of the greatest thinkers, and one of the greatest composers. To hear him talk, he was Shakespeare, and Beethoven, and Plato, rolled into one. He was one of the most exhausting conversationalists that ever lived. Sometimes he was brilliant; sometimes he was maddeningly tiresome. But whether he was being brilliant or dull, he had one sole topic of conversation: himself. What he thought and what he did. 3He had a mania for being in the right. The slightest hint of disagreement, from anyone, on the most trivial point, was enough to set him off on a harangue that might last for hours, in which he proved himself right in so many ways, and with such exhausting volubility, that in the end his hearer, stunned and deafened, would agree with him, for the sake of peace. 4It never occurred to him that he and his doing were not of the most intense and fascinating interest to anyone with whom he came in contact. He had theories about almost any subject under the sun, including vegetarianism, the drama, politics, and music; and in support of these theories he wrote pamphlets, letters, books ... thousands upon thousands of words, hundreds and hundreds of pages. He not only wrote these things, and published them ― usually at somebody else’s expense ― but he would sit and read them aloud, for hours, to his friends, and his family. 5He had the emotional stability of a six-year-old child. When he felt out of sorts, he would rave and stamp, or sink into suicidal gloom and talk darkly of going to the East to end his days as a Buddhist monk. Ten minutes later, when something pleased him he would rush out of doors and run around the garden, or jump up and down off the sofa, or stand on his head. He could be grief-stricken over the death of a pet dog, and could be callous and heartless to a degree that would have made a Roman emperor shudder. 6He was almost innocent of any sense of responsibility. He was convinced that
高中语文必修一背诵篇目 1、《沁园春长沙》毛泽东 独立寒秋，湘江北去，橘子洲头。 看万山红遍，层林尽染；漫江碧透，百舸争流。 鹰击长空，鱼翔浅底，万类霜天竞自由。 怅寥廓，问苍茫大地，谁主沉浮？ 携来百侣曾游，忆往昔峥嵘岁月稠。 恰同学少年，风华正茂；书生意气，挥斥方遒。 指点江山，激扬文字，粪土当年万户侯。 曾记否，到中流击水，浪遏飞舟？ 2、《诗两首》 （1）、《雨巷》戴望舒 撑着油纸伞，独自 /彷徨在悠长、悠长/又寂寥的雨巷， 我希望逢着 /一个丁香一样的 /结着愁怨的姑娘。 她是有 /丁香一样的颜色，/丁香一样的芬芳， /丁香一样的忧愁， 在雨中哀怨， /哀怨又彷徨； /她彷徨在这寂寥的雨巷， 撑着油纸伞 /像我一样， /像我一样地 /默默彳亍着 冷漠、凄清，又惆怅。 /她静默地走近/走近，又投出 太息一般的眼光，/她飘过 /像梦一般地， /像梦一般地凄婉迷茫。 像梦中飘过 /一枝丁香的， /我身旁飘过这女郎； 她静默地远了，远了，/到了颓圮的篱墙， /走尽这雨巷。 在雨的哀曲里， /消了她的颜色， /散了她的芬芳， /消散了，甚至她的 太息般的眼光， /丁香般的惆怅/撑着油纸伞，独自 /彷徨在悠长，悠长 又寂寥的雨巷， /我希望飘过 /一个丁香一样的 /结着愁怨的姑娘。 （2）、《再别康桥》徐志摩 轻轻的我走了， /正如我轻轻的来； /我轻轻的招手， /作别西天的云彩。 那河畔的金柳， /是夕阳中的新娘； /波光里的艳影， /在我的心头荡漾。 软泥上的青荇， /油油的在水底招摇； /在康河的柔波里， /我甘心做一条水草！那榆阴下的一潭， /不是清泉，是天上虹 /揉碎在浮藻间， /沉淀着彩虹似的梦。寻梦？撑一支长篙， /向青草更青处漫溯， /满载一船星辉， /在星辉斑斓里放歌。但我不能放歌， /悄悄是别离的笙箫； /夏虫也为我沉默， / 沉默是今晚的康桥！悄悄的我走了， /正如我悄悄的来；/我挥一挥衣袖， /不带走一片云彩。 4、《荆轲刺秦王》 太子及宾客知其事者，皆白衣冠以送之。至易水上，既祖，取道。高渐离击筑，荆轲和而歌，为变徵之声，士皆垂泪涕泣。又前而为歌曰：“风萧萧兮易水寒，壮士一去兮不复还！”复为慷慨羽声，士皆瞋目，发尽上指冠。于是荆轲遂就车而去，终已不顾。 5、《记念刘和珍君》鲁迅 （1）、真的猛士，敢于直面惨淡的人生，敢于正视淋漓的鲜血。这是怎样的哀痛者和幸福者？然而造化又常常为庸人设计，以时间的流驶，来洗涤旧迹，仅使留下淡红的血色和微漠的悲哀。在这淡红的血色和微漠的悲哀中，又给人暂得偷生，维持着这似人非人的世界。我不知道这样的世界何时是一个尽头！
必修1 沁园春·长沙（全文）毛泽东 独立寒秋， 湘江北去， 橘子洲头。 看万山红遍， 层林尽染， 漫江碧透， 百舸争流。 鹰击长空， 鱼翔浅底， 万类霜天竞自由。 怅寥廓， 问苍茫大地， 谁主沉浮。 携来百侣曾游， 忆往昔峥嵘岁月稠。 恰同学少年， 风华正茂， 书生意气， 挥斥方遒。 指点江山， 激扬文字， 粪土当年万户侯。 曾记否， 到中流击水， 浪遏飞舟。 雨巷（全文）戴望舒 撑着油纸伞，独自 彷徨在悠长、悠长 又寂寥的雨巷， 我希望逢着 一个丁香一样地 结着愁怨的姑娘。 她是有 丁香一样的颜色， 丁香一样的芬芳， 丁香一样的忧愁， 在雨中哀怨， 哀怨又彷徨；
她彷徨在这寂寥的雨巷， 撑着油纸伞 像我一样， 像我一样地 默默彳亍着 冷漠、凄清，又惆怅。 她默默地走近， 走近，又投出 太息一般的眼光 她飘过 像梦一般地， 像梦一般地凄婉迷茫。 像梦中飘过 一枝丁香地， 我身旁飘过这个女郎； 她默默地远了，远了， 到了颓圮的篱墙， 走尽这雨巷。 在雨的哀曲里， 消了她的颜色， 散了她的芬芳， 消散了，甚至她的 太息般的眼光 丁香般的惆怅。 撑着油纸伞，独自 彷徨在悠长、悠长 又寂寥的雨巷， 我希望飘过 一个丁香一样地 结着愁怨的姑娘。 再别康桥（全文）徐志摩 轻轻的我走了，正如我轻轻的来；我轻轻的招手，作别西天的云彩。 那河畔的金柳，是夕阳中的新娘；波光里的艳影，在我的心头荡漾。 软泥上的青荇，油油的在水底招摇；
在康河的柔波里，我甘心做一条水草！ 那榆荫下的一潭，不是清泉， 是天上虹揉碎在浮藻间，沉淀着彩虹似的梦。 寻梦？撑一支长篙，向青草更青处漫溯， 满载一船星辉，在星辉斑斓里放歌。 但我不能放歌，悄悄是别离的笙箫； 夏虫也为我沉默，沉默是今晚的康桥。 悄悄的我走了，正如我悄悄的来； 我挥一挥衣袖，不带走一片云彩。 记念刘和珍君（二、四节）鲁迅 二 真的猛士，敢于直面惨淡的人生，敢于正视淋漓的鲜血。这是怎样的哀痛者和幸福者？然而造化又常常为庸人设计，以时间的流驶，来洗涤旧迹，仅使留下淡红的血色和微漠的悲哀。在这淡红的血色和微漠的悲哀中，又给人暂得偷生，维持着这似人非人的世界。我不知道这样的世界何时是一个尽头！ 我们还在这样的世上活着；我也早觉得有写一点东西的必要了。离三月十八日也已有两星期，忘却的救主快要降临了罢，我正有写一点东西的必要了。 四 我在十八日早晨，才知道上午有群众向执政府请愿的事；下午便得到噩耗，说卫队居然开枪，死伤至数百人，而刘和珍君即在遇害者之列。但我对于这些传说，竟至于颇为怀疑。我向来是不惮以最坏的恶意，来推测中国人的，然而我还不料，也不信竟会下劣凶残到这地步。况且始终微笑着的和蔼的刘和珍君，更何至于无端在府门前喋血呢？ 然而即日证明是事实了，作证的便是她自己的尸骸。还有一具，是杨德群君的。而且又证明着这不但是杀害，简直是虐杀，因为身体上还有棍棒的伤痕。 但段政府就有令，说她们是“暴徒”！ 但接着就有流言，说她们是受人利用的。 惨象，已使我目不忍视了；流言，尤使我耳不忍闻。我还有什么话可说呢？我懂得衰亡民族之所以默无声息的缘由了。沉默啊，沉默啊！不在沉默中爆发，就在沉默中灭亡。
Unit 5 THE MONSTER He was an undersized little man, with a head too big for his body -- a sickly little man. His nerves were had. He had skin trouble. It was agony for him to wear anything next to his skin coarser than silk. And he had seclusions of grandeur. He was a monster of conceit.Never for one minute did he look at the world or at people, except in relation to himself. He was not only the most important person in the world,to himself;in his own eyes he was the only person who existed. He believed himself to be one of the greatest dramatists in the world, one of the greatest thinkers, and one of the greatest composers. To hear him talk, he was Shakespeare, and Beethoven, and Plato, rolled into one. And you would have had no difficulty in hearing him talk. He was one of the most exhausting conversationalists that ever lived. An evening with him was an evening spent in listening to a monologue. Sometimes he was brilliant; sometimes he was maddeningly tiresome. But whether he was being brilliant or dull, he had one sole topic of conversation: himself. What he thought and what he did. He had a mania for being in the right.The slightest hint of disagreement,from anyone, on the most trivial point, was enough to set him off on a harangue that might last for house, in which he proved himself right in so many ways, and with such exhausting volubility, that in the end his hearer, stunned and deafened, would agree with him, for the sake of peace. It never occurred to him that he and his doing were not of the most intense and fascinating interest to anyone with whom he came in contact.He had theories about almost any subject under the sun, including vegetarianism, the drama, politics, and music; and in support of these theories he wrote pamphlets,le tters, books? thousands upon thousands of words, hundreds and hundreds of pages. He not only wrote these things, and published them -- usually at somebody else's expense-- but he would sit and read them aloud, for hours, to his friends and his family. He wrote operas,and no sooner did he have the synopsis of a story, but he would invite -- or rather summon -- a crowed of his friends to his house, and read it aloud to them. Not for criticism. For applause. When the complete poem was written, the friends had to come again,and hear that read aloud.Then he would publish the poem, sometimes years before the music that went with it was written. He played the piano like a composer, in the worst sense of what that implies, and he would sit down at the piano before parties that included some of the finest pianists of his time, and play for them, by the hour, his own music, needless to say. He had a composer's voice. And he would invite eminent vocalists to his house and sing them his operas, taking all the parts.
最新资料欢迎阅读 Unit 7 The Monster课文翻译综合教程四 Unit 7 The Monster Deems Taylor 1 He was an undersized little man, with a head too big for his body ― a sickly little man. His nerves were bad. He had skin trouble. It was agony for him to wear anything next to his skin coarser than silk. And he had delusions of grandeur. 2 He was a monster of conceit. Never for one minute did he look at the world or at people, except in relation to himself. He believed himself to be one of the greatest dramatists in the world, one of the greatest thinkers, and one of the greatest composers. To hear him talk, he was Shakespeare, and Beethoven, and Plato, rolled into one. He was one of the most exhausting conversationalists that ever lived. Sometimes he was brilliant;sometimes he was maddeningly tiresome. But whether he was being brilliant or dull, he had one sole topic of conversation: himself. What he thought and what he did. 3 He had a mania for being in the right. The slightest hint of disagreement, from anyone, on the most trivial point, was enough to set him off on a harangue that might last for hours, in which he proved himself right in so many ways, and with such exhausting volubility, that in the end his hearer, stunned and deafened, would agree with him,for the sake of peace. 4 It never occurred to him that he and his doing were not of the most intense and fascinating interest to anyone with whomhe came in contact. He had theories about almost any subject under the sun,including vegetarianism, the drama, politics, and music; and in support of these theories he wrote pamphlets, letters,books ... thousands upon thousands
人教版高中语文必修(1-5)必背课文.txt6宽容润滑了彼此的关系，消除了彼此的隔阂，扫清了彼此的顾忌，增进了彼此的了解。人教版高中语文必修（1-5）必背课文 诗★诗★诗 ★卫风?氓（背诵全文）《诗经》 氓之蚩蚩，抱布贸丝。匪来贸丝，来即我谋。送子涉淇，至于顿丘。匪我愆期，子无良媒。将子无怒，秋以为期。 乘彼垝垣，以望复关。不见复关，泣涕涟涟。既见复关，载笑载言。尔卜尔筮，体无咎言。以尔车来，以我贿迁。 桑之未落，其叶沃若。于嗟鸠兮，无食桑葚！于嗟女兮，无与士耽！士之耽兮，犹可说也。女之耽兮，不可说也。 桑之落矣，其黄而陨。自我徂尔，三岁食贫。淇水汤汤，渐车帷裳。女也不爽，士贰其行。士也罔极，二三其德。 三岁为妇，靡室劳矣；夙兴夜寐，靡有朝矣。言既遂矣，至于暴矣。兄弟不知，咥其笑矣。静言思之，躬自悼矣。 及尔偕老，老使我怨。淇则有岸，隰则有泮。总角之宴，言笑晏晏。信誓旦旦，不思其反。反是不思，亦已焉哉！ ★涉江采芙蓉（背诵全文）古诗十九首 涉江采芙蓉,兰泽多芳草。采之欲遗谁?所思在远道。 还顾望旧乡,长路漫浩浩。同心而离居,忧伤以终老。 ★秋兴八首(其一)（背诵全文）杜甫 玉露凋伤枫树林，巫山巫峡气萧森。江间波浪兼天涌，塞上风云接地阴。 丛菊两开他日泪，孤舟一系故园心。寒衣处处催刀尺，白帝城高急暮砧。 ★咏怀古迹(其三)（背诵全文）杜甫 群山万壑赴荆棘，生长明妃尚有村。一去紫台连朔漠，独留青冢向黄昏。 画图省识春风面，环佩空归月夜魂。千载琵琶作胡语，分明怨恨曲中论。 ★登高（背诵全文）杜甫 风急天高猿啸哀，渚清沙白鸟飞回。无边落木萧萧下，不尽长江滚滚来。 万里悲秋常作客，百年多病独登台。艰难苦恨繁霜鬓，潦倒新停浊酒杯。 ★锦瑟（背诵全文）李商隐 锦瑟无端五十弦，一弦一柱思华年。庄生晓梦迷蝴蝶，望帝春心托杜鹃。 沧海月明珠有泪，蓝田日暖玉生烟。此情可待成追忆，只是当时已惘然。 ★马嵬李商隐 海外徒闻更九州，他生未卜此生休。空闻虎旅传宵柝，无复鸡人报晓筹。 此日六军同驻马，当时七夕笑牵牛。如何四纪为天子，不及卢家有莫愁！ ★蜀道难（背诵全文）李白
unit 1 Mr. Doherty Builds His Dream Life In America many people have a romantic idea of life in the countryside. Many living in towns dream of starting up their own farm, of living off the land. Few get round to putting their dreams into practice. This is perhaps just as well, as the life of a farmer is far from easy, as Jim Doherty discovered when he set out to combine being a writer with running a farm. Nevertheless, as he explains, he has no regrets and remains enthusiastic about his decision to change his way of life. 在美国，不少人对乡村生活怀有浪漫的情感。许多居住在城镇的人梦想着自己办个农场，梦想着靠土地为生。很少有人真去把梦想变为现实。或许这也没有什么不好，因为，正如吉姆·多尔蒂当初开始其写作和农场经营双重生涯时所体验到的那样，农耕生活远非轻松自在。但他写道，自己并不后悔，对自己作出的改变生活方式的决定仍热情不减。 Mr. Doherty Builds His Dream Life Jim Doherty There are two things I have always wanted to do -- write and live on a farm. Today I'm doing both. I am not in E. B. White's class as a writer or in my neighbors' league as a farmer, but I'm getting by. And after years of frustration with city and suburban living, my wife Sandy and I have finally found contentment here in the country. 多尔蒂先生创建自己的理想生活吉姆·多尔蒂有两件事是我一直想做的――写作与务农。如今我同时做着这两件事。作为作家，我和E·B·怀特不属同一等级，作为农场主，我和乡邻也不是同一类人，不过我应付得还行。在城市以及郊区历经多年的怅惘失望之后，我和妻子桑迪终于在这里的乡村寻觅到心灵的满足。 It's a self-reliant sort of life. We grow nearly all of our fruits and vegetables. Our hens keep us in eggs, with several dozen left over to sell each week. Our bees provide us with honey, and we cut enough wood to just about make it through the heating season. 这是一种自力更生的生活。我们食用的果蔬几乎都是自己种的。自家饲养的鸡提供鸡蛋，每星期还能剩余几十个出售。自家养殖的蜜蜂提供蜂蜜，我们还自己动手砍柴，足可供过冬取暖之用。 It's a satisfying life too. In the summer we canoe on the river, go picnicking in the woods and take long bicycle rides. In the winter we ski and skate. We get excited about sunsets. We love the smell of the earth warming and the sound of cattle lowing. We watch for hawks in the sky and deer in the cornfields. 这也是一种令人满足的生活。夏日里我们在河上荡舟，