DOI: 10.1126/science.1230612
, 1587 (2012);
338 Science et al.Nuno L. Barbosa-Morais Species
The Evolutionary Landscape of Alternative Splicing in Vertebrate
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w w w .s c i e n c e m a g .o r g D o w n l o a d e d f r o m
octatomic S,dimethyltrisulfide,and dimethyl-tetrasulfide,the latter two for about a combined 1mmole/g;the fragment contained in addition only naphthalene at2to8nmol/g,plus methyl-naphthalenes and biphenol in subnanomole amounts, but no alkanes or anthracene/phenanthrene.
The SM meteorite demonstrates that the com-plexity of C-class asteroid surfaces is greater than previously assumed.Rapid terrestrial alteration probably erases many vestiges of the internal and external processes on the asteroid that remain to be explored in spacecraft sample-return missions.
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Acknowledgments:The rapid recovery of SM was made possible
by the local communities of Lotus,Coloma,Pilot Hill,and Grass
Valley,due in part to the support of property owners,community
leaders,SETI Institute and University of Caifornia at Davis(UC Davis)
student and volunteer searchers,and officials of the Marshall
Gold Discovery State Historic Park and the State of California.We
thank J.Howard,M.Carter,D.E.Macon,and L.Hofland of the
NASA Ames Research Center;M.Hill of the American Museum of
Natural History;and G.Baxter,N.Botto,D.Rowland,O.Kreylos,
L.Kellogg,and D.Summer of UC Davis for assistance with reported
measurements.The NASA Ames Research Center–coordinated
search efforts were supported by the NASA Lunar Science Institute.
E.D.Y.,M.Z.,A.M.D.,D.S.E.,J.E.E.,K.N.,K.C.W.,M.H.T.,M.W.C.,
Q.-Z.Y.,and S.B.S.acknowledge the NASA Cosmochemistry Program
for support of work reported here.In addition,the following
NASA programs are sincerely acknowledged:Near Earth Object
Observation Program(P.J.),Origins of Solar Systems(S.A.S.),
Planetary Major Equipment(Q.-Z.Y.),Sample Return Laboratory
Instruments and Data Analysis(M.W.C.),the NASA Astrobiology
Institute(J.E.E.,J.P.D.,and D.P.G.),the SPring-8Grant Program
(M.Z.),and Post Doctoral Programs(A.S.B.).P.R.H.acknowledges
support from the Tawani Foundation.R.O.acknowledges KAKENHI
grants from the Japan Society for the Promotion of Science.
Supplementary Materials
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Materials and Methods
Supplementary Text
Figs.S1to S36
Tables S1to S22
References(49–105)
9July2012;accepted12November2012
10.1126/science.1227163
The Evolutionary Landscape
of Alternative Splicing in Vertebrate Species
Nuno L.Barbosa-Morais,1,2Manuel Irimia,1*Qun Pan,1*Hui Y.Xiong,3*Serge Gueroussov,1,4* Leo J.Lee,3Valentina Slobodeniuc,1Claudia Kutter,5Stephen Watt,5Recep?olak,1,6 TaeHyung Kim,1,7Christine M.Misquitta-Ali,1Michael D.Wilson,4,5,7Philip M.Kim,1,4,6 Duncan T.Odom,5,8Brendan J.Frey,1,3Benjamin J.Blencowe1,4?
How species with similar repertoires of protein-coding genes differ so markedly at the phenotypic level is poorly understood.By comparing organ transcriptomes from vertebrate species spanning~350million years of evolution,we observed significant differences in alternative splicing complexity between vertebrate lineages,with the highest complexity in primates.Within6million years,the splicing profiles of physiologically equivalent organs diverged such that they are more strongly related to the identity of a species than they are to organ type.Most vertebrate species-specific splicing patterns are cis-directed. However,a subset of pronounced splicing changes are predicted to remodel protein interactions involving trans-acting regulators.These events likely further contributed to the diversification of splicing and other transcriptomic changes that underlie phenotypic differences among vertebrate species.
V ertebrate species possess diverse phe-notypic characteristics,yet they share
similar repertoires of coding genes(1).Evolutionary changes in transcriptomes under-
lie structural and regulatory differences asso-
ciated with species-specific characteristics.For
example,species-dependent mRNA and non-
coding RNA(ncRNA)expression patterns have
been linked to mutational changes in cis-and
trans-acting regulatory factors,as well as to phe-
notypic differences(2–5).However,because
organ-dependent mRNA expression levels with-
in individual species have been largely con-
served during vertebrate evolution(6,7),it seems
unlikely that changes in gene expression(GE)
1Banting and Best Department of Medical Research,Donnelly
Centre,University of Toronto,Toronto,Ontario M5S3E1,Cana-
da.2Instituto de Medicina Molecular,Faculdade de Medicina,
Universidade de Lisboa,1649-028Lisboa,Portugal.3Department
of Electrical and Computer Engineering,University of Toronto,
Toronto,Ontario M5S3G4,Canada.4Department of Molec-
ular Genetics,University of Toronto,Toronto,Ontario M5S1A8,
Canada.5University of Cambridge,CRUK-Cambridge Institute,
Robinson Way,Cambridge CB20RE,UK.6Department of Com-
puter Science,University of Toronto,Toronto,Ontario M5S
2E4,Canada.7Hospital for Sick Children,Toronto,Ontario
M5G1X8,Canada.8Wellcome Trust Sanger Institute,Genome
Campus,Hinxton,Cambridge CB101SA,UK.
*These authors contributed equally to this work.
?To whom correspondence should be addressed.E-mail:
b.blencowe@utoronto.ca
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RESEARCH ARTICLES
account for the majority of phenotypic diver-sity among vertebrates.
Through the variable use of cis-acting RNA elements in exons and flanking introns that are recognized by trans-acting factors,different pairs of splice sites in primary transcripts can be se-lected in a cell type–,condition-,or species-
specific manner(8–15).Changes in alternative
splicing(AS)may therefore represent a major
source of species-specific differences(16–25).
Here,we describe a genome-wide investigation
of AS differences among physiologically equiv-
alent organs from vertebrate species spanning the
major tetrapod lineages.
Evolution of alternative splicing complexity.
High-throughput RNA sequencing(RNA-Seq)
data were collected from whole brain,forebrain
cortex,cerebellum,heart,skeletal muscle,
liver, Fig.1.Profiling of alternative splicing(AS)in vertebrates.(A)Relative
proportions of exons undergoing AS in each sample,as measured by de-
tection of middle exon skipping in random exon triplets,where the three
exons are represented by orthologs in the analyzed species(y-axis units
relative to the sample with lowest AS frequency).See fig.S1,A and B,for a
more detailed version;see table S5for details on samples,including rep-
licates,and RNA-Seq data sets.(B)Percentage of common AS events be-
tween human and other species.(C)Symmetrical heat map of Spearman
correlations from PSI profiles.For each sample,PSI values for the1550
orthologous exons in the11analyzed species were estimated.See fig.S4A
for a more detailed version.(D)Symmetrical heat map of Pearson correla-
tions from gene expression(GE)profiles.For each sample,mRNA expres-
sion[log cRPKM values(26)]of1809analyzed orthologous genes in the
11analyzed species were estimated.Key as in(C).See fig.S4B for a more
detailed version.(E)Heat map of PSI values for41conserved cassette al-
ternative exons.Rows,exons;columns,samples.Key as in(C).See fig.S11B
for a more detailed version.Data are hierarchically clustered(complete meth-
od,Euclidean distance)for heat maps in(C)to(E).
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kidney,and testis from human,chimpanzee,orang-utan,macaque,mouse,opossum,platypus,chick-en,lizard,and frog (26).For each species,we considered all internal exons as potential cassette AS events and created nonredundant databases of splice junction sequences formed by inclusion or skipping of each exon.RNA-Seq reads were mapped to the junction databases to determine “percent spliced-in ”(PSI)values,and also to rep-resentative transcript sequences from each gene to estimate GE levels,represented as “corrected reads per kilobase transcript model per million mapped reads ”(cRPKM)values (26).Orthology relation-ships between genes and exons were established to enable direct cross-species comparisons.The relative proportions of orthologous exons detected to undergo AS in each sample were de-termined.Equal numbers of reads were randomly sampled from each RNA-Seq data set to control for coverage differences (26).AS detection is ap-proximately twice as frequent in all analyzed pri-mate organs as in the equivalent organs from mouse and other species (Fig.1A and fig.S1).Moreover,there is an overall decline in AS fre-quency as the evolutionary distance from primates increases.These differences are significant (P <10?10,Mann-Whitney U tests),are robust to dif-ferent methods of AS frequency detection,and are independent of the variability in AS detection rates between individuals within the same spe-cies (Fig.1A and fig.S1).Genes with the highest AS complexity in human are significantly en-riched in cytoskeleton-associated functions (P <0.03)(table S1),which suggests that AS-directed diversification of the cytoskeleton may have been a driving force in the evolution of increased cel-lular complexity in vertebrate species.
Rapid evolution of organ-specific alternative splicing.We next compared AS profiles across organs and species.Approximately half of al-ternatively spliced exons among species sepa-rated by ~6million years of evolution are different
(Fig.1B and figs.S2A and S3A).When clus-tering organ AS profiles on the basis of how overall PSI values correlate in pairwise compar-isons,the samples segregate by individual spe-cies (Fig.1C and fig.S4A).This is in contrast to clustering samples on the basis of how their overall GE levels correlate,where the samples segregate according to tissue type (Fig.1D and fig.S4B)(6,7).Principal components analysis confirms that species type and tissue type are the primary sources of variability underlying the overall AS and GE patterns,respectively (figs.S5and S6).The species-dependent clustering of AS profiles is also observed when analyzing sub-sets of alternative exons associated with a wide range of splice site strengths,exon length,increased magnitudes of PSI change between tissues,increased read coverage,and also when using indepen-dently validated (16)PSI differences (figs.S7to S10).These results indicate that overall organ-specific AS patterns have evolved at a much more rapid rate than organ-specific GE patterns.However,when restricting the clustering anal-ysis to all (n =41)orthologous exons that are alternatively spliced in four species (human,mouse,chicken,and frog)representing the main tetrapod lineages,the samples segregate by tis-sue type,with similar results obtained with the larger data set of tissues and species (Fig.1E and fig.S11,A to H).The 41exons,on average,display a wider range of inclusion levels across the samples,indicating that they have a higher degree of regulatory potential (fig.S11I).Con-sistent with this observation,they are also asso-ciated with elevated exonic and flanking intronic sequence conservation,implying that they are under increased selection pressure to maintain binding sites for regulatory trans-acting factors (26).Therefore,although overall AS patterns of multiple organs distinguish vertebrate species,a small subset of exons that undergo AS in multi-ple species spanning ~350million years of evo-lution display conserved patterns of regulation that reflect organ type.
We next investigated the relative rates at which AS and GE have evolved.From pairwise comparisons of PSI values in homologous tissues,we observe an overall increase of PSI diver-gence from human with evolutionary time (Fig.2A).In contrast to results from analyzing GE di-vergence (Fig.2,C and D)(6,7),AS levels in testis have not diverged more rapidly than in other tissues (Fig.2B),and AS events detected in neural tissues display the slowest rate of divergence (P <10?6,Mann-Whitney U tests).A significantly higher proportion (27%more on average)of neural AS events are conserved between vertebrate species than are AS events specific to other organs (P <0.002,Mann-Whitney U test;fig.S2B).These AS events are enriched in genes associated with synaptic transmission,axon guidance,neural de-velopment,and actin cytoskeleton reorganization (table S2),indicating that AS regulation of these processes is a highly conserved feature of ver-tebrate nervous system development.
A
B
C
D
0100200300400
0.6
0.7
0.8
0.9Divergence from Human (Ma)
P e a r s o n c o r r e l a t i o n o f G E w / H u m a
n
C h i m p O r a n g u t a n M a c a q u e
M o u s e
O p o s s u m P l a t y p u s
F r o g
C h i c k e n L i z a r d
cortex/brain cerebellum liver kidney heart muscle testis
P u f f e r f i s h
T r e e l e n g t h
brain
01002003004000.0
0.2
0.40.6
Divergence from Human (Ma)
P e a r s o n c o r r e l a t i o n o f A S w / H u m a
n
cortex/brain cerebellum liver kidney heart muscle testis
C h i m p O r a n g u t a n M a c a q u e
M o u s e
O p o s s u m P l a t y p u s
F r o g
C h i c k e n L i z a r d
P u f f e r f i s h
brain
T r e e l e n g t h
Fig.2.Different rates of AS and GE divergence.(A )Pearson correlations between human and other species when comparing PSI values pairwise for conserved tissue-specific alternative exons in each tissue.For each pair of samples,correlation is analyzed for PSI values for all exons undergoing AS in both samples.(B )Comparisons of total tree lengths (bootstrapping,100replicates)of PSI trees for con-served tissue-specific alternative exons from six tissues in seven species (human,chimp,macaque,mouse,opossum,platypus,chicken).Statistically significant differences between the neural and each of the other tissues are indicated (Mann-Whitney U tests).Full PSI trees for each tissue are shown in fig.S3B.(C )Pearson correlations between human and other species when comparing GE pairwise (cRPKM,log scale;1809orthologous genes in the 11analyzed species)in each organ.(D )Comparisons of total tree lengths (bootstrapping,100replicates)of expression trees from analyzing six organs from seven species as in (B).Statistically significant differences between testis and each of the other tissues are indicated (Mann-Whitney U tests).Full expression trees for each tissue are shown in fig.S3C.
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Evolution of vertebrate splicing codes.To investigate mechanisms underlying the diver-gence in organ AS profiles,we used a splicing code derived from mouse data (27,28)to com-pare cis-regulatory elements that are predictive of tissue-dependent splicing patterns of five or-gans (brain,heart,skeletal muscle,liver,and kid-ney)from the four representative species analyzed above.The splicing code achieved high classi-fication rates when predicting organ-specific AS patterns from sequence alone.The average true positive rate [AUC,area under the receiver op-erating characteristic (ROC)curve]ranges from 68to 70%for heart exon skipping to 80to 88%for brain exon inclusion (Fig.3,A and B,and fig.S12).An exception was a subset of approximate-ly 200exon-skipping AS events in human brain,
which were predicted less well (AUC =62%)(fig.S12)(26).
A comparison of the most strongly predictive cis-elements accounting for each species ’organ-dependent splicing patterns revealed that these significantly overlap in most tissues (Fig.3C and fig.S12).Such cis-elements may represent features comprising an ancestral vertebrate splic-ing code (Fig.3D).However,the overlap between sets of splicing code features used in a given pair of species decreases with increased evolutionary distance (Fig.3C and fig.S12;see also below).Thus,organ-dependent AS patterns appear to be generally controlled by significantly overlapping cis-regulatory codes,although progressive diver-gence in these codes likely also contributes to AS differences.
Species-specific alternative splicing is primar-ily cis-directed.The extent to which evolutionary change in cis-regulatory codes (versus trans-acting factors)accounts for species-dependent AS differences is not known.To address this,we used a mouse strain,Tc1,carrying the ma-jority of human chromosome 21(HsChr21)(29).We compared PSI values of exons from HsChr21transcripts expressed in multiple organs (brain,liver,heart,testis)from the Tc1strain,with PSI values of the identical exons in the correspond-ing human organs.We also compared PSI val-ues for the orthologous mouse exons between wild-type and Tc1mouse strains.For all com-parisons,we analyzed a comprehensive set of 13HsChr21and orthologous mouse exons that were detected,using RNA-Seq data,
to
Fig.3.Inference and comparative analysis of vertebrate splicing codes.(A )ROC curves of splicing code predictions for brain-dependent exon inclusion in human,mouse,chicken,and frog.ROC curves for other tissues are shown in fig.S12.(B )AUC in percent for each of the ROC curves in (A).(C )Left:Heat map of splicing code features with significant prediction scores associated with brain-specific exon inclusion in each species (red for P <0.05,Mann-Whitney U test);statistically significant features in common with all significant mouse features associated with brain-specific exon inclusion are shown.Right:Pro-portions of features significantly associated with mouse brain-specific exon inclusion also significant for brain-specific exon inclusion in other species.Error bars:95%confidence intervals,Pearson ’s c 2proportion tests.Analyses of predictive features for other tissues are shown in fig.S12.(D )Region-specific distribution of code features significantly associated with tissue-specific exon inclusion or exclusion in all four species,as determined by their region-specific enrichment or by their predictive power as inferred by the splicing code.Splicing factors associated with code features are in square brackets.Significantly enriched features are indicated by hollow arrows;features both significantly enriched and predictive are indicated by bold arrows.Arrows are colored according to the organ with which the features are associated (refer to key).21DECEMBER 2012VOL 338
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have undergone AS in at least one of the two species.
All analyzed HsChr21exons that are alterna-tively spliced in human for which the orthologous exons in mouse are constitutively spliced are also alternatively spliced in the Tc1mouse;likewise,all HsChr21constitutively spliced exons for which the orthologous exons in mouse are alternatively spliced are also constitutively spliced in the Tc1mouse (P <0.02,both comparisons;one-sided Fisher ’s exact tests;Fig.4,A and B,and fig.S13A).For the orthologous exons that are alternatively spliced in human and mouse,we observe a sig-nificantly higher correlation between their inclu-sion levels in Tc1mouse and normal human organs relative to the correlation observed when comparing inclusion levels of all orthologous hu-man and mouse exons (r =0.89versus r =0.52,P <0.0008,one-sided Z-test;fig.S13B)(26).Collectively,the results indicate that changes among predominantly conserved cis-regulatory elements are sufficient to direct the majority of the species-specific AS patterns,at least in hu-man and mouse.However,because our results also indicate that vertebrate splicing codes di-verged with increasing evolutionary distance,and because specific subsets of AS events could not be reliably predicted using the splicing code,changes in trans-acting factors likely also con-tributed to evolutionary differences in AS.
Species-classifying alternative splicing events in trans-acting regulatory factors.To investigate which splicing changes during evolution likely had the greatest functional impact,we identified AS events that best discriminate or “classify ”spe-cies (26).These AS events have relatively large and widely expressed PSI differences between species or lineages,and were validated at a high rate by reverse transcription polymerase chain reaction (RT-PCR)assays (r =0.90,n =180;fig.S14).Gene Ontology enrichment analysis re-veals that the corresponding genes are function-ally diverse,with “nucleic acid binding ”among the most frequently represented categories (Fig.5A,fig.S14,and tables S3and S4).Consistent with a major role for conserved cis-regulatory elements governing species-dependent AS pro-files (Figs.3and 4),the species-classifying AS events are significantly underrepresented in exons that overlap nucleic acid binding domains,rela-tive to other classes of alternative exons in the same genes (P <0.04,Pearson ’s c 2proportion test;Fig.5C).
An interesting example of a species-classifying AS event is the activity-modulating exon 9of the splicing regulator PTBP1,located between RNA recognition motifs 2and 3in this protein (30,31).This exon is skipped in mammalian organs but is fully included in chicken and frog organs (Fig.5A).Consistent with the possibility of a more
variable and extensive regulatory role for PTBP1in mammalian-specific AS,we observe signifi-cant enrichment of putative PTBP1binding sites in sequences surrounding mammalian-specific AS events relative to sequences surrounding chicken-and frog-specific AS events (P <0.002,one-sided Fisher ’s exact test;Fig.5B).
The species-classifying AS events in genes as-sociated with other functions are also significantly underrepresented in exons that overlap folded protein domains (P <0.0002,Pearson ’s c 2pro-portion test;fig.S15A).However,the species-classifying AS events are significantly enriched in frame-preserving exons relative to nonclassify-ing species-specific AS events (P ≤0.05,Pearson ’s c 2proportion test;Fig.5D and fig.S15B),and they are also enriched in protein regions pre-dicted to be disordered.Disordered regions gen-erally reside on protein surfaces and are known to play critical roles in ligand interactions and cell signaling (32,33),and recent work has shown that tissue-regulated exons enriched in predicted disordered sequences often function in remodel-ing protein-protein interactions (PPIs)(34,35).The species-classifying AS events thus possess multiple features of functionally important exons.Discussion.Our results show that organs of primate species have significantly higher cas-sette exon AS frequencies than do organs of other vertebrate species.Moreover,overall organ AS
PSI Human Mouse
P S I T c
1
A
B
Fig.4.Human-specific AS is preserved in a mouse trans-acting environment.(A )Scatterplot comparing RT-PCR –estimated PSI values for HsChr21exons in human tissues (squares)or for the orthologous exons in the corresponding wild-type mouse tissues (triangles)(x
axis),and the same HsChr21exons in Tc1mouse tissues (y axis)[13different pairs of orthologous exons,31total pairs of orthologous AS events (26)].Data points are colored according to whether the represented splicing events are alternative in human and constitutive in mouse (red),constitutive in human and alternative in mouse (blue),or alternative in both species (black)(26).Dark blue:exons with PSI >95%and <100%in human and PSI <50%in mouse.Identity line is in dashed gray.P values for one-sided Fisher ’s exact tests are indicated.(B )RT-PCR experiments measuring PSI levels for pairs of orthologous human and mouse exons using species-specific primer pairs (26),for exons
alternative in one species and constitutive or near-constitutive (PSI >95%)in the other.Human Chr21exons were analyzed in Tc1mouse tissues and normal human tissues;the orthologous mouse exons were analyzed in corresponding tissues from both the Tc1and wild-type mouse strains.Quantification of PSI levels,human gene names (followed by the exon number,when more than one exon for the same gene was studied),and tissues are indicated.Red and yellow dots indicate exon-included and exon-skipped isoforms,respectively.Note that each set of species-specific primers amplifying the orthologous splice isoforms generates size-distinct RT-PCR https://www.doczj.com/doc/f411850256.html,
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Fig.5.Characterization of species-classifying AS events.(A )Domain diagrams and RT-PCR experiments measuring PSI levels for representative species-classifying AS events.Predicted highly disordered protein regions are depicted by red bars above the domain diagrams.Human gene names are indicated,as are the locations of the classifying alternative exon,species,and organs (B,brain;L,liver;K,kidney;H,heart;M,muscle)in which the validations were performed,as well as quantification of PSI levels.Red and yellow dots indicate exon-included and exon-skipped isoforms,respectively.RT-PCR assays were performed as in Fig.4.(B )Comparisons of the average number of PTBP1-related cis-features asso-ciated with mammalian-classifying and nonclassifying species-dependent AS events,and the corresponding classes of species-dependent AS events in chicken and frog.Error bars:95%confidence intervals,Pearson ’s c 2proportion tests.Statistically significant differences are indicated.(C )Comparison of the proportion of residues in different types of coding exons in proteins with nucleic acid –binding domains that overlap folded protein domains.Classes of alternative exons (red bars)analyzed are (i)“species-classifiers,”AS events that discriminate species;(ii)“conserved AS,”exons detected as AS in at least two of the analyzed species;and
(iii)“species-specific AS,”exons that are alternatively spliced in only one of the analyzed species.For each class of alternative exon,distal constitutive exons (separated from the alternative exon by at least two exons)in the same genes are analyzed (yellow bars).“Background constitutive ”refers to all exons that are constitutively spliced in all tissues (white bars).Error bars:95%confidence inter-vals,Pearson ’s c 2proportion tests.Statistically significant differences between species-classifying AS events and each of the other classes of AS events are indicated.(D )Proportion of exons in proteins with nucleic acid binding domains that preserve the reading frame when included/skipped in transcripts (3n exons,exons with nucleotide length multiple of three nucleotides).Types of exons analyzed are as in (C).Error bars:95%confidence intervals,Pearson ’s c 2proportion tests.Statistically significant differences between species-classifying AS events and the other species-specific AS events are indicated.(E )Proportion of predicted intrinsically disordered amino acids in different classes of exons in proteins with nucleic acid binding domains,as described in (C).Error bars denote SE of the associated distributions.Statistically significant differences between species-classifying AS events and the other species-specific AS events are indicated (Student ’s t test).21DECEMBER 2012VOL 338
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profiles more strongly reflect the identity of a spe-cies than they do organ type.This contrasts with organ-dependent differences in mRNA expres-sion,which are largely conserved throughout vertebrate evolution[this study and(6,7)].We propose that the rapid divergence in AS patterns in vertebrate organs may have played a more widespread role in shaping species-specific dif-ferences than did changes in mRNA expression.
Our work offers conclusive evidence that the reassortment of splicing code features can ac-count for the majority of AS differences between vertebrate species.Consistent with this observa-tion,species-classifying exons identified in this study are often found in genes encoding trans-acting regulators but are underrepresented in the nucleic acid binding domains of these proteins. Instead,they are highly enriched in disordered regions,which are known to function in signaling and in mediating PPIs.Because these AS changes affect trans-acting factors involved in gene regu-lation,they represent an additional mechanistic basis for the remarkable diversification in AS and other transcriptomic changes associated with phenotypic change among vertebrate species.
References and Notes
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Acknowledgments:We thank H.Han,D.O’Hanlon,
M.Lukk,and the Cambridge Research Institute Biorepository,
Genomics,and Bioinformatics Units for expert assistance;
V.Tybulewicz,E.Fisher,R.Cohen,J.Wade,D.Simpson,and
J.Gurdon for tissues and mouse strains;and T.Hughes,
C.Ouzounis,F.Roth,and past and present members of the
Blencowe laboratory for helpful discussions and comments on
the manuscript.Supported by grants from the Canadian
Institutes of Health Research(B.J.B.and B.J.F.);Canadian
Cancer Society(B.J.B.);Genome Canada(through the Ontario
Genomics Institute)and the Ontario Research Fund(B.J.B.,
B.J.F.and others);Natural Sciences and Engineering Research
Council of Canada(B.J.F.);EMBO YIP and ERC starting Grants
(D.T.O.);CIHR postdoctoral and Marie Curie IOF fellowships
(N.L.B.-M.);an SNF postdoctoral fellowship(C.K.);an NSERC
studentship(S.G.);and a Human Frontiers Science Program
Organization long-term fellowship(M.I.).RNA-Seq data sets
analyzed in this study can be accessed through GEO
(GSE41338,GSE30352)and ArrayExpress(E-MTAB-513).
Supplementary Materials
https://www.doczj.com/doc/f411850256.html,/cgi/content/full/338/6114/1587/DC1
Materials and Methods
Supplementary Text
Figs.S1to S15
Tables S1to S9
References(36–78)
24September2012;accepted14November2012
10.1126/science.1230612
Evolutionary Dynamics of Gene
and Isoform Regulation in Mammalian Tissues
Jason Merkin,1Caitlin Russell,1Ping Chen,1,3Christopher B.Burge1,2*
Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing,but the extent of splicing conservation is not clear.To assess tissue-specific transcriptome variation across mammals,we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate,at unprecedented depth.We find that while tissue-specific gene expression programs are largely conserved,alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific.Thousands of previously unknown,lineage-specific, and conserved alternative exons were identified;widely conserved alternative exons had signatures of binding by MBNL,PTB,RBFOX,STAR,and TIA family splicing factors,implicating them as ancestral mammalian splicing regulators.Our data also indicate that alternative splicing often alters protein phosphorylatability,delimiting the scope of kinase signaling.
A lternative pre-mRNA processing can
result in mRNA isoforms that encode
distinct protein products,or may differ exclusively in untranslated regions,potentially affecting mRNA stability,localization,or trans-lation(1).It can also produce nonfunctional mRNAs that are targets of nonsense-mediated mRNA decay,serving to control gene expression (2).Most human alternative splicing is tissue-regulated(3,4),but the extent to which tissue-specific splicing patterns are conserved across mammalian species has not yet been compre-
hensively studied.
To address outstanding questions about the
conservation and functional importance of tissue-
specific splicing,we conducted transcriptome
sequencing(RNA-Seq)analysis of nine tissues
from five vertebrates,consisting of four mammals
and one bird.The species,chosen on the basis of
the quality of their genomes(all high-coverage
finished or draft genomes)and their evolutionary
relationships,include the rodents mouse and rat,
the rhesus macaque,a nonrodent/nonprimate
boroeutherian,cow,and chicken as an outgroup.
These relationships allow for the evaluation of
transcriptome changes between species with di-
vergence times ranging from<30million years to
>300million years(Fig.1A).Our sequencing
strategy used paired-end short or long read se-
quencing of poly(A)-selected RNA.In total,we
generated more than16billion reads(>8billion
read pairs)totaling over1trillion bases(3,5)
(table S1).The data were mapped to the relevant
genomes with software that can identify novel
splice junctions and isoforms(6).
To assess coverage of genes,we compared
these de novo annotations with existing Ensembl
annotations.We detected>211,000(97%)of the
~217,000annotated exons in mouse,and sim-
ilarly high fractions in most other species,in-
cluding more than99%of exons in chicken
(table S1).We estimated that nearly all multi-
exonic genes in the species studied are alterna-
tively spliced(fig.S1)(3).
1Department of Biology,Massachusetts Institute of Tech-
nology,Cambridge,MA02142,USA.2Department of Bio-
logical Engineering,Massachusetts Institute of Technology,
Cambridge,MA02142,USA.3Systems Biology Laboratory,
Research Programs Unit,Genome-Scale Biology and Institute
of Biomedicine,Biochemistry and Developmental Biology,
University of Helsinki,Haartmaninkatu8,Helsinki,FIN-00014,
Finland.
*To whom correspondence should be addressed.E-mail:
cburge@https://www.doczj.com/doc/f411850256.html,
https://www.doczj.com/doc/f411850256.html, SCIENCE VOL33821DECEMBER20121593
RESEARCH ARTICLES
首届“教育教学技能大比武”总结 为期半个月的青年教师首届“教育教学技能大比武”活动已经圆满落下帷幕。参加本次比赛的教师都是38周岁以下的青年教师，比赛内容包括讲课、答辩、三笔字、演讲四个环节。这次活动在学校领导的大力支持下，在全体教师的努力配合下，在参赛教师积极参与、认真准备下，取得圆满成功。 回顾本次比赛活动，老师们无论是在个人综合素质、教材把握能力还是在课堂驾驭能力上都有精彩的展示，下面对本次活动做一个总结： 一、讲课赛环节 这十九位青年教师对此次比赛高度重视，认真备课、讲课，为我们呈现了一节节风格各异、亮点纷呈的课，主要呈现了一下几个特点： 1、备课充分、设计用心。 老师们在备课过程中，能深入钻研教材，做了大量充分的准备。老师们都精心设计导语，创设情境，千方百计地激发起学生强烈的求知欲，能够把知识和能力深入浅出又扎扎实实的传授给学生，每一节课都朴实无华，每一节课都独具匠心，比如：郑珊老师在讲授《图形的旋转》一课时，教学设计层次分明，抓住平移和旋转的特征明确其描述方法，在新授的过程中能够放手让学生自己思考-动手操作-小组交流-展示（说明描述），老师引导学生亲历学习过程，通过几个有效的追问，使自己体会掌握了学习内容。 2、教学扎实有效，注重基础训练。 老师们能够抓住教学目标，精心设计每一个环节，同时老师们十分注重基础训练，比如高年级语文老师在教学中注重字词的品读与指导，在阅读教学中，老师能通过阅读来领悟文本的内涵，例如王玉英讲述《梅花魂》一课，她更注重引导学生“品词、品句、品读”以此让学生以读明理，以读悟情，通过“品”字让学生真正体会到了外祖父为什么那么珍爱墨梅图，从而理解梅花的品行，上升到中国人的气节。语文中低年级教学中，教师注重字形的书写字文的理解和区别运用，比如赵彤霞老师执教《植物妈妈有办法》一课，能在文中恰到好处的让学生理解“许多”和“许”“多”的区别，并用“纷纷”说一句话。又比如赵志芳执教《秋天的雨》一课中，注重了“爽”字的书写指导，教学中注重句子的训练，让学生练说比喻句。 3、注重学生情感态度和学习习惯的培养。 注重学生情感态度和学习习惯的培养是成为这次比赛课的又一亮点。老师们在教学中，做到自始至终关注学生的情感，营造宽松、民主、和谐的教学气氛，尊重每个学生，积极鼓励他们在学习中的尝试，保护他们的自尊心和积极性。比如吴蕊霞老师的鼓励具有个性化，激励性的语言常挂嘴边，成为学生不断学习、创新不可缺乏的精神动力。同时在教学中注重学习习惯的培养，比如高月枝老师在授课的同时适时对学生进行了课常规的教育，整个一节课，教学秩序井然有序，对于刚上学两个星期的孩子真的很难得。 4、善用多媒体教学。 本次讲课赛几乎所有的老师都制作了精美实用的多媒体课件，追求既生动形象又快捷高效的教学效果。特别是赵丽和龚伟科两位老师用我们上学期培训的知识制作了白板课件。 5、教师素养良好。 通过这次比赛，我们欣喜地看到我校青年教师具备良好的教师基本素质。他们教态大方得体，语言清晰，具有较强的亲和力和应变能力。王敏、陈蓉等老师她们在课堂上文雅得体的教态，丰富的肢体语言以及亲切和蔼的微笑，都给我们留下了深刻的印象，深受学生的喜爱。 针对本次讲课赛反映出的问题，给老师们提出以下建议，跟老师们商榷：1、语文教学中，略读课文的教学教师应大胆放手学生，让学生充分展示自己。有感情的朗读，重在先理解再
The way 的用法 Ⅰ常见用法： 1)the way+ that 2)the way + in which（最为正式的用法） 3)the way + 省略（最为自然的用法） 举例：I like the way in which he talks. I like the way that he talks. I like the way he talks. Ⅱ习惯用法： 在当代美国英语中，the way用作为副词的对格，“the way+ 从句”实际上相当于一个状语从句来修饰整个句子。 1)The way =as I am talking to you just the way I’d talk to my own child. He did not do it the way his friends did. Most fruits are naturally sweet and we can eat them just the way they are—all we have to do is to clean and peel them. 2）The way= according to the way/ judging from the way The way you answer the question, you are an excellent student. The way most people look at you, you’d think trash man is a monster. 3）The way =how/ how much No one can imagine the way he missed her. 4）The way =because
教师即兴演讲题目之63个话题 来源：思雨教育资源网|教学资源|课件论文|作文作者：无边思雨发表日期：2009-5-30 13:16:19 阅读次数： 910 查看权限：普通文章 1、如何维护班集体荣誉？ 2、如何看待学生时代早恋问题？ 3、成人与成才二者是怎样的关系？结合实例说明自己的观点。 4、不同地域、不同背景、不同习惯的同学之间该如何相处？ 5、怎样面对学习、生活中遇到的挫折？ 6、你最崇拜的人是谁？“名人”还是自己？ 7、你认为我们是否应有感恩之心？感恩于谁？ 8、你希望自己会是怎样一位老师？你会如何教育自己的学生？ 9、“言行、仪表”与个人的发展。 10、如今继续提倡“勤俭、节约”作风是否已过时？ 11、在各种资料、媒体中常讲张扬个性，你认为我们该张扬什么样的个性？ 12、三轮车工人方尚礼自己生活的如乞丐，却将自己蹬车收入的35万多元用来资助失学儿童，当病重时，社会捐助给他治病的钱，也被他捐给了希望工程。你对方尚礼的这种行为有何评述？ 13、电视广告不宜过多 14、保护环境是每个人的责任 15、我中学时代的一个朋友 16、世界需要热心肠 17、向权威挑战 18、2008年的我 19、我爱电视广告 20、我的母亲 21、尊重是孩子成长的基石 22、如何培养学生的好奇心 23、推广普通话 24、“恶语伤人六月寒” 25、我心中的偶像 26、假如我是画家 27、童年趣事 28、珍惜现在 29、我最爱看的电视节目 30、有人认为老师是不断燃烧的蜡烛，你认为呢？ 31、新课程背景下良好师生场的营造。 32、让谐趣幽默走进我们的课堂。 33、阅读教学中如何开展有效的对话教学？ 34、如何正确处理价值取向和个性化阅读的关系？ 35、新课程背景下一堂好课的标准是什么？ 36、“语文教学工具性与人文性统一”的内涵是什么？ 37、如何实践语文教学的人文性和工具性的“统一”？ 38、如何挖掘教材资源，准确选点，扎实训练？
The way的用法及其含义（二） 二、the way在句中的语法作用 the way在句中可以作主语、宾语或表语： 1.作主语 The way you are doing it is completely crazy.你这个干法简直发疯。 The way she puts on that accent really irritates me. 她故意操那种口音的样子实在令我恼火。The way she behaved towards him was utterly ruthless. 她对待他真是无情至极。 Words are important, but the way a person stands, folds his or her arms or moves his or her hands can also give us information about his or her feelings. 言语固然重要,但人的站姿,抱臂的方式和手势也回告诉我们他(她)的情感。 2.作宾语 I hate the way she stared at me.我讨厌她盯我看的样子。 We like the way that her hair hangs down.我们喜欢她的头发笔直地垂下来。 You could tell she was foreign by the way she was dressed. 从她的穿著就可以看出她是外国人。 She could not hide her amusement at the way he was dancing. 她见他跳舞的姿势，忍俊不禁。 3.作表语 This is the way the accident happened.这就是事故如何发生的。 Believe it or not, that's the way it is. 信不信由你, 反正事情就是这样。 That's the way I look at it, too. 我也是这么想。 That was the way minority nationalities were treated in old China. 那就是少数民族在旧中
定冠词the的用法： 定冠词the与指示代词this ,that同源,有“那(这)个”的意思,但较弱,可以和一个名词连用,来表示某个或某些特定的人或东西. (1)特指双方都明白的人或物 Take the medicine.把药吃了. (2)上文提到过的人或事 He bought a house.他买了幢房子. I've been to the house.我去过那幢房子. (3)指世界上独一无二的事物 the sun ,the sky ,the moon, the earth (4)单数名词连用表示一类事物 the dollar 美元 the fox 狐狸 或与形容词或分词连用,表示一类人 the rich 富人 the living 生者 (5)用在序数词和形容词最高级,及形容词等前面 Where do you live?你住在哪? I live on the second floor.我住在二楼. That's the very thing I've been looking for.那正是我要找的东西. (6)与复数名词连用,指整个群体 They are the teachers of this school.(指全体教师) They are teachers of this school.(指部分教师) (7)表示所有,相当于物主代词,用在表示身体部位的名词前 She caught me by the arm.她抓住了我的手臂. (8)用在某些有普通名词构成的国家名称,机关团体,阶级等专有名词前 the People's Republic of China 中华人民共和国 the United States 美国 (9)用在表示乐器的名词前 She plays the piano.她会弹钢琴. (10)用在姓氏的复数名词之前,表示一家人 the Greens 格林一家人(或格林夫妇) (11)用在惯用语中 in the day, in the morning... the day before yesterday, the next morning... in the sky... in the dark... in the end... on the whole, by the way...
“tｈｅwａｙ+从句”结构的意义及用法 首先让我们来看下面这个句子: Ｒead the foｌloｗｉnｇpassagｅａnd talkａbout ｉt wi ｔh your classmaｔes．Try tｏｔeｌl whaｔyｏu thiｎk ｏf Tom aｎd ｏｆｔhe ｗay the chiｌｄrenｔrｅated ｈim. 在这个句子中，ｔhe waｙ是先行词,后面是省略了关系副词that或in whｉch的定语从句。 下面我们将叙述“the ｗaｙ+从句”结构的用法。 1.tｈe wａy之后，引导定语从句的关系词是tｈat而不是hoｗ,因此，<<现代英语惯用法词典＞＞中所给出的下面两个句子是错误的：Ｔhｉs is ｔｈeｗayｈowｉtｈａppened. This is the way how he ａlwａｙs treats me. 2．在正式语体中,thaｔ可被in which所代替;在非正式语体中，ｔhat则往往省略。由此我们得到theｗay后接定语从句时的三种模式：1) tｈe ｗaｙ＋ｔhａt-从句２）the way +ｉn whiｃh－从句3) the ｗay +从句 例如：Ｔｈe way(in whiｃh ，thａt) ｔhｅｓｅｃomｒade ｓloｏｋａｔｐrobｌems is wrong．这些同志看问题的方法
不对。 Ｔｈｅｗａy(that ,ｉn ｗhiｃh)yoｕ’ｒe doinｇit is comple ｔeｌy crａzy.你这么个干法,简直发疯。 Wｅａdmiｒｅd him for thｅｗay ｉｎｗhｉch he fａｃeｓdiｆficultieｓ． Waｌlａｃe ａｎd Ｄarwiｎｇreed ｏn the way ｉｎwhi ｃh ｄｉfｆｅrｅnt forms ｏf life had ｂegｕn.华莱士和达尔文对不同类型的生物是如何起源的持相同的观点。 Thｉs is ｔｈe ｗaｙ（tｈａｔ) hｅdｉd it. I lｉkeｄｔhe waｙ(ｔhat) ｓｈeｏｒganized ｔhe ｍeetｉng． 3.theｗay(tｈat)有时可以与hｏw(作“如何”解）通用。例如： That’s tｈe ｗaｙ(tｈaｔ) shｅspoke. = Tｈat’s how shｅspoke.
表示“方式”、“方法”，注意以下用法： 1.表示用某种方法或按某种方式，通常用介词in(此介词有时可省略)。如： Do it (in) your own way. 按你自己的方法做吧。 Please do not talk (in) that way. 请不要那样说。 2.表示做某事的方式或方法，其后可接不定式或of doing sth。 如： It’s the best way of studying [to study] English. 这是学习英语的最好方法。 There are different ways to do [of doing] it. 做这事有不同的办法。 3.其后通常可直接跟一个定语从句(不用任何引导词)，也可跟由that 或in which 引导的定语从句，但是其后的从句不能由how 来引导。如： 我不喜欢他说话的态度。 正：I don’t like the way he spoke. 正：I don’t like the way that he spoke. 正：I don’t like the way in which he spoke. 误：I don’t like the way how he spoke. 4.注意以下各句the way 的用法： That’s the way (=how) he spoke. 那就是他说话的方式。 Nobody else loves you the way(=as) I do. 没有人像我这样爱你。 The way (=According as) you are studying now, you won’tmake much progress. 根据你现在学习情况来看，你不会有多大的进步。 2007年陕西省高考英语中有这样一道单项填空题： ——I think he is taking an active part insocial work. ——I agree with you_____. A、in a way B、on the way C、by the way D、in the way 此题答案选A。要想弄清为什么选A，而不选其他几项，则要弄清选项中含way的四个短语的不同意义和用法，下面我们就对此作一归纳和小结。 一、in a way的用法 表示：在一定程度上，从某方面说。如： In a way he was right.在某种程度上他是对的。注：in a way也可说成in one way。 二、on the way的用法 1、表示：即将来(去)，就要来(去)。如： Spring is on the way.春天快到了。 I'd better be on my way soon.我最好还是快点儿走。 Radio forecasts said a sixth-grade wind was on the way.无线电预报说将有六级大风。 2、表示：在路上，在行进中。如： He stopped for breakfast on the way.他中途停下吃早点。 We had some good laughs on the way.我们在路上好好笑了一阵子。 3、表示：(婴儿)尚未出生。如： She has two children with another one on the way.她有两个孩子，现在还怀着一个。 She's got five children，and another one is on the way.她已经有5个孩子了，另一个又快生了。 三、by the way的用法
青年教师朗诵比赛活动方案 （2014----2015）学年度下学期 一、活动目的： 学校是推广普通话，规范语言文字的主阵地，教师作为推广普通话的中坚力量有着不可忽视的重要作用。因此，为了加强教师基本功训练，提升教师的朗读水平，教导处根据语言文字规范化活动计划，开展以“朗读美文展我风采”的教师朗诵比赛。通过教师美文朗读比赛，提高我校青年教师普通话水平，营造浓厚的校园读书氛围，提升教师教学基本功，促使教师重视朗读教学，促进学生健康和谐发展。 二、活动组织：教导处 三、具体活动安排： 1、培训时间：6月8日（周一）下午14:30 2、比赛时间：6月15日（周一）下午14:30 3、比赛地点：四楼舞蹈室 4、参赛人员：35岁以下（含35岁）青年教师必须参加，同时欢迎35岁以上教师参加。 5、比赛内容：作品自选，体裁不限（不少于三分钟） 6、比赛形式：可配乐，参赛人员独立诵读。 7、评委：黄冬梅蒋丽丽郭艳华贺芳刘忠霞冷静武玉德 8、分数统计：王辉赵慧贤
9、主持：徐金凤 四、活动程序： 1、学校将在赛前一周邀请校长对参赛人员进行培训。 2、参赛教师提前十分钟到达比赛场地，做好准备工作。 3、14:40正式进行比赛，按抽签顺序进行。 4、评分办法：比赛采取现场评分的办法，满分10分，比赛结束后，进行分数汇总、统计，取平均分，宣布比赛成绩。 5、校长点评并作总结。 五、设奖情况： 本次比赛将设一等奖2名，二等奖3名，三等奖5名，优秀奖若干名。比赛成绩计入年末教师量化考核。 六、朗诵比赛评分标准 （一）、主题内容（2分） 1、内容（1分）：题材不限，内容健康向上；充实生动，有真情实意 2、主题（1分）：寓意深刻，富有感召力 （二）、普通话（3分） 1、发音（1分）：语音准确1分，较准确0.8分，基本准确0.5分，不准确不得分。 2、语速（1分）：语速恰当、声音洪亮，表达自然流畅1分，因不熟练，每停顿一次扣0.1分。
青年教师基本功大赛即兴演讲题目【题目1】我的兴趣爱好【题目2】谈谈内心和谐【题目3】人最难超越的高度就是自己【题目4】我的价值观【题目5】谈谈与人相处【题目6】坚守心灵的一方沃土【题目7】给快乐找个理由【题目8】年轻 没有什么不可以【题目9】心底无私天地宽【题目10】人是需要一点精神的【题目11】我们与时代同行【题目12】生活从“心”开始【题目13】让更多的人快乐 【题目14】面对繁杂的教学工作 你如何调整心态 【题目15】和谐、健康、快乐【题目16】我喜爱的书刊【题目17】你如何发展自己的专业弱点【题目18】善待自己 呵护希望【题目18】.上公开课对一个教师的成长的作用【题目19】培养积极心态 感悟责任人生【题目24】永不言弃 我心永恒 准备时间 3分钟 【题目25】.你怎样做个身心健康的老师【题目26】你如何看待家长满意工程 【题目27】新课程执行过程中 你碰到最棘手的问题是什么【题目28】课堂教学中 你最关注的是什么【题目29】你希望学校领导关心青年教师哪些方面【题目30】谈谈自己的业余生活【题目31】简评最近的工作情况。【题目32】怎样才能提高教师的凝聚力。【题目33】.谈谈做班主任的心得【题目34】.你怎样定义教师【题目35】简介杨森中学【题目36】.点评一位我校的优秀教师【题目37】.如何看待家长的不理解【题目38】.谈谈卫生与健康【题目39】谈谈我校的环境. 【题目40】谈谈如何管理学生【题目41】谈谈你对职业道德的认识【题目42】我参加校本研修之感想。【题目43】“依法治教 注重服务 着力塑造行业形象” 请你谈谈你的设想【题目44】.如何发挥你校师生之特长 【题目45】.怎样调动老师的工作积极性 【题目46】.谈谈你对校本教研的看法。【题目47】.我是怎样备课的。【题目48】.维持校门口的秩序 我的一点想法。【题目49】如何丰富教师的业余生活 缓解教师的心理压力 【题目50】谈谈你对节日文化的认识【题目51】学校活动很多的情况下 你如何调节自己的心态 【题目52】德育倡导“全面德育 全员德育” 请你谈谈自己的理解。【题目53】如何让家长尊重教师 【题目54】你认为提高教育质量应从哪里抓起【题目55】从哪些方面帮助班主任管理学生篇二：教师即兴演讲题目之63个话题 教师即兴演讲题目之63个话题 来源：思雨教育资源网|教学资源|课件论文|作文作者：无边思雨发表日期：2009-5-30 13:16:19 阅读次数： 910 查看权限：普通文章 1、如何维护班集体荣誉？ 2、如何看待学生时代早恋问题？ 3、成人与成才二者是怎样的关系？结合实例说明自己的观点。 4、不同地域、不同背景、不同习惯的同学之间该如何相处？ 5、怎样面对学习、生活中遇到的挫折？ 6、你最崇拜的人是谁？“名人”还是自己？ 7、你认为我们是否应有感恩之心？感恩于谁？ 8、你希望自己会是怎样一位老师？你会如何教育自己的学生？ 9、“言行、仪表”与个人的发展。 10、如今继续提倡“勤俭、节约”作风是否已过时？ 11、在各种资料、媒体中常讲张扬个性，你认为我们该张扬什么样的个性？ 12、三轮车工人方尚礼自己生活的如乞丐，却将自己蹬车收入的35万多元用来资助失学儿童，当病重时，社会捐助给他治病的钱，也被他捐给了希望工程。你对方尚礼的这种行为有何评述？ 13、电视广告不宜过多 14、保护环境是每个人的责任
The way的用法及其含义（一） 有这样一个句子：In 1770 the room was completed the way she wanted. 1770年，这间琥珀屋按照她的要求完成了。 the way在句中的语法作用是什么？其意义如何？在阅读时，学生经常会碰到一些含有the way 的句子，如：No one knows the way he invented the machine. He did not do the experiment the way his teacher told him.等等。他们对the way 的用法和含义比较模糊。在这几个句子中，the way之后的部分都是定语从句。第一句的意思是，“没人知道他是怎样发明这台机器的。”the way的意思相当于how；第二句的意思是，“他没有按照老师说的那样做实验。”the way 的意思相当于as。在In 1770 the room was completed the way she wanted.这句话中，the way也是as的含义。随着现代英语的发展，the way的用法已越来越普遍了。下面，我们从the way的语法作用和意义等方面做一考查和分析： 一、the way作先行词，后接定语从句 以下3种表达都是正确的。例如：“我喜欢她笑的样子。” 1. the way+ in which +从句 I like the way in which she smiles. 2. the way+ that +从句 I like the way that she smiles. 3. the way + 从句(省略了in which或that) I like the way she smiles. 又如：“火灾如何发生的，有好几种说法。” 1. There were several theories about the way in which the fire started. 2. There were several theories about the way that the fire started.
教师基本功是教师从事教育教学工作必须具备的最基本的职业技能。它包括通用于所有教师的一般基本功，也包括学科教学和教育工作的基本功。教师基本功是加强青年教师职业道德建设的一项重要内容，也是教师从事教育教学工作必须具备的最基本的职业技能。如果说教学是技术加艺术，那么这种技术和艺术主要表现在教师课堂教学的基本功上面。它是教师素质的重要表现，也是教学成败的关键。过去所说的教师基本功，无非是三字一画（钢笔、毛笔、粉笔字和简笔画）和语文基础知识、口头表达能力等，再加上一些专业学科的基本功（音乐、体育、美术等）。在新一轮的课程改革中，需要我们重新看待教师的教学基本功。随着时代的发展，教师基本功的含义越来越广，教 师基本功包括的范围越来越大。下面我谈谈自己对教师应该具备的基本功的认识。 一、为人师表教师基本功应以德为先，教师的基本素质首当其冲的是师德素质。 我认为教师首先要有高尚的师德，只有思想上以学生为本，有做名师的愿望，至少有一个积极健康的心态，才能练好基本功。 1、有理想，有事业心。 2、以身作则学校无小事，处处皆教育，教师一言一行都会对学生造成影响。 二、爱的能力教师做的是人的工作，应该有人文素质，在爱
人过程中进行教育教学工作。爱学生也是一种技能，爱他们，使他们 容易、愉悦接受。 三、表达能力. 1、语言表达普通话是教师的职业语言，教师能用普通话进 行教学，普通话一般应达到国家语委制定的《普通话水平测试》二级水平。 2、文字表达教师的工作比较繁重，但是要学会反思和总结， 把心得体会写出来，才能少走弯路，更快进步，摆脱烦琐；才能轻松、高效的工作。 四、动手能力. 1、三笔一画这是传统意义的教师基本功。 2、板书板书不仅表现出一位教师上课的基本功，而且也体现教师的教学态度乃至性格。 3、运用、制作教具使用、制作教具方面，能按教学要求，正确使用教具；能就地取材，制作简易的教具。 4、现代信息技术的掌握和运用。 5、演示一般教师的演示指教态，教师也要做一个演员。 五、备课能力
way 的用法 【语境展示】 1. Now I’ll show you how to do the experiment in a different way. 下面我来演示如何用一种不同的方法做这个实验。 2. The teacher had a strange way to make his classes lively and interesting. 这位老师有种奇怪的办法让他的课生动有趣。 3. Can you tell me the best way of working out this problem? 你能告诉我算出这道题的最好方法吗？ 4. I don’t know the way (that / in which) he helped her out. 我不知道他用什么方法帮助她摆脱困境的。 5. The way (that / which) he talked about to solve the problem was difficult to understand. 他所谈到的解决这个问题的方法难以理解。 6. I don’t like the way that / which is being widely used for saving water. 我不喜欢这种正在被广泛使用的节水方法。 7. They did not do it the way we do now. 他们以前的做法和我们现在不一样。 【归纳总结】 ●way作“方法，方式”讲时，如表示“以……方式”，前面常加介词in。如例1； ●way作“方法，方式”讲时，其后可接不定式to do sth.，也可接of doing sth. 作定语，表示做某事的方法。如例2，例3；
教师基本功是什么1 我们常说“教学基本功”如何如何，多指教师的专业功底，教学基本技能，教学方法以及由此产生的教学效果等等，放在一个讨论教师质量和教育教学质量的背景下，我们是不是关注一下：什么是教师基本功呢？ 基本素质 教师的基本素质首当其冲的是师德素质。师德不能等同于职业道德，但却函盖职业道德。我觉得职业道德主要是针对物品或没生命的，或有生命也不是传道授业与做人思想工作的。教师的职业道德重要的在于“师”字上，即为人师的职业道德。只是时下还有多少人能够有称职的师德呢？！当下的教育环境下，教师一方面普遍出现职业倦怠，一方面却又师德开始退化！教师的现状让人担忧！ 我觉得，教师的基本素质应还包括人文素养，没有人文素养的教师眼中根本就不会有“人”的存在，也就不会在新课程中体现“以人为本”的理念，更不会在课堂上有“生命的气息”！我觉得人文素养应该尊重生命、尊重人的尊严，还要包括带头遵守社会文明公约、法律法规等，并成为践行的时代先锋。也就是说，教师还要在遵守社会文明等方面真正为人师表！ 基本知识 教师职业的特殊性，必然要求每一个教师要具备一定的基本知识，即包括教育理论、学科知识、心理学知识等。教师教育理论的丰厚与否往往束缚一个教师的发展与理论素养的高低，甚至影响到教师的教育思想与个人成长;而学科知识除了学科的相关基础知识外，还应包括学科的前沿知识；因为现在的学生压力大，心理又非常脆弱，这就给教师的教育工作增加了难度，因此，教师的基本知识应该要有心理辅导的知识，再说，当下的教师工作压力大，许多教师心理也存在一定的问题，他们本身更需要心理的自我调适能力。 基本能力 教师应具备的基本能力是什么呢？我认为应该是学习能力、科研能力、解决问题能力、写作能力、组织教学能力、协作能力等。 知识日新月异，特别是网络的盛行，让知识的传播与创新更快，因此，教师如果没有学习能力，就不能与时俱进，便会成为时代的落后者，这会影响到教师自身的发展与教育水平高低。况且，现在对于终身教育或终身学习理念的倡导，作为一名教师更应该成为这一理念的先驱。 科研能力是不是教师的必备能力？或者说教师要不要搞教育科研？我觉得不一定每一个教师都要成为研究型教师与专家型教师，但具备一定的教育科研能力，或了解教育科研的方法，或参与并体验科学研究的过程，应该是教师要积极投入的一种体验。而且，当前新课程提倡的探究性学习或研究性学习，本身就是要培养学生的科学素养与科学精神！如果教师不具备
小学英语教师基本功比赛朗读材料-MY DREAM My Dream Everyone has a lot of dreams. Some people want to be rich, dreaming of becoming millionaires [m?lj?'ne?] overnight. Others want to be famous, dreaming of suddenly jumping to great fame. I have a lot of dreams,too. When I was a young girl, I dreamed of becoming a scientist like Hua Iuogen in future. However, I knew very well that I could not succeed without painstaking ['pe?nzte?k??]efforts. So I studied hard in the middle school and college in order to attain my goal. After graduating from college, I found a job as a teacher. Although I was very busy with teaching, I never gave up my goal. I read a lot of books to get more knowledge. I made experiments to practice and apply what I had learnt from the books. Sometimes, I was so deeply indulged [?n'd?ld?] in my research that I forgot my meals and time. Now I have made great progress. Several of my research papers have been published. The methods ['meθ?d] proposed in my papers have been proven
t h e-w a y-的用法
The way 的用法 "the way+从句"结构在英语教科书中出现的频率较高, the way 是先行词, 其后是定语从句.它有三种表达形式:1) the way+that 2)the way+ in which 3)the way + 从句(省略了that或in which),在通常情况下, 用in which 引导的定语从句最为正式,用that的次之,而省略了关系代词that 或 in which 的, 反而显得更自然,最为常用.如下面三句话所示,其意义相同. I like the way in which he talks. I like the way that he talks. I like the way he talks. 一.在当代美国英语中,the way用作为副词的对格,"the way+从句"实际上相当于一个状语从句来修饰全句. the way=as 1)I'm talking to you just the way I'd talk to a boy of my own. 我和你说话就象和自己孩子说话一样. 2)He did not do it the way his friend did. 他没有象他朋友那样去做此事. 3)Most fruits are naturally sweet and we can eat them just the way they are ----all we have to do is clean or peel them . 大部分水果天然甜润,可以直接食用,我们只需要把他们清洗一下或去皮.
教师基本功即兴演讲 【篇一：青年教师基本功大赛即兴演讲题目】 青年教师基本功大赛即兴演讲题目【题目1】我的兴趣爱好【题目2】谈谈内心和谐【题目3】人最难超越的高度就是自己【题目4】 我的价值观【题目5】谈谈与人相处【题目6】坚守心灵的一方沃 土【题目7】给快乐找个理由【题目8】年轻?没有什么不可以 【题目9】心底无私天地宽【题目10】人是需要一点精神的【题目11】我们与时代同行【题目12】生活从“心”开始【题目13】让更 多的人快乐?【题目14】面对繁杂的教学工作?你如何调整心态 ?【题目15】和谐、健康、快乐【题目16】我喜爱的书刊【题目17】你如何发展自己的专业弱点【题目18】善待自己?呵护希望 【题目18】.上公开课对一个教师的成长的作用【题目19】培养积 极心态?感悟责任人生【题目24】永不言弃?我心永恒?准备时间 ?3分钟?【题目25】.你怎样做个身心健康的老师【题目26】你如何看待家长满意工程?【题目27】新课程执行过程中?你碰到最棘 手的问题是什么【题目28】课堂教学中?你最关注的是什么【题目29】你希望学校领导关心青年教师哪些方面【题目30】谈谈自己的 业余生活【题目31】简评最近的工作情况。【题目32】怎样才能 提高教师的凝聚力。【题目33】.谈谈做班主任的心得【题目34】. 你怎样定义教师【题目35】简介杨森中学【题目36】.点评一位我 校的优秀教师【题目37】.如何看待家长的不理解【题目38】.谈谈 卫生与健康【题目39】谈谈我校的环境. 【题目40】谈谈如何管理 学生【题目41】谈谈你对职业道德的认识【题目42】我参加校本 研修之感想。【题目43】“依法治教?注重服务?着力塑造行业形 象”?请你谈谈你的设想【题目44】.如何发挥你校师生之特长? 【题目45】.怎样调动老师的工作积极性?【题目46】.谈谈你对校 本教研的看法。【题目47】.我是怎样备课的。【题目48】.维持校 门口的秩序?我的一点想法。【题目49】如何丰富教师的业余生活 ?缓解教师的心理压力?【题目50】谈谈你对节日文化的认识【题 目51】学校活动很多的情况下?你如何调节自己的心态?【题目52】德育倡导“全面德育?全员德育”?请你谈谈自己的理解。【题目53】如何让家长尊重教师?【题目54】你认为提高教育质量应从哪里抓 起【题目55】从哪些方面帮助班主任管理学生 【篇二：教师基本功即兴演讲需要准备几分钟】
way的用法总结大全 way的用法你知道多少，今天给大家带来way的用法，希望能够帮助到大家，下面就和大家分享，来欣赏一下吧。 way的用法总结大全 way的意思 n. 道路,方法,方向,某方面 adv. 远远地，大大地 way用法 way可以用作名词 way的基本意思是“路,道,街,径”,一般用来指具体的“路,道路”,也可指通向某地的“方向”“路线”或做某事所采用的手段,即“方式,方法”。way还可指“习俗,作风”“距离”“附近,周围”“某方面”等。 way作“方法,方式,手段”解时,前面常加介词in。如果way前有this, that等限定词,介词可省略,但如果放在句首,介词则不可省略。
way作“方式,方法”解时,其后可接of v -ing或to- v 作定语,也可接定语从句,引导从句的关系代词或关系副词常可省略。 way用作名词的用法例句 I am on my way to the grocery store.我正在去杂货店的路上。 We lost the way in the dark.我们在黑夜中迷路了。 He asked me the way to London.他问我去伦敦的路。 way可以用作副词 way用作副词时意思是“远远地,大大地”,通常指在程度或距离上有一定的差距。 way back表示“很久以前”。 way用作副词的用法例句 It seems like Im always way too busy with work.我工作总是太忙了。 His ideas were way ahead of his time.他的思想远远超越了他那个时代。 She finished the race way ahead of the other runners.她第一个跑到终点,远远领先于其他选手。 way用法例句
t h e_w a y的用法大全
The way 在the way+从句中, the way 是先行词, 其后是定语从句.它有三种表达形式:1) the way+that 2)the way+ in which 3)the way + 从句(省略了that或in which),在通常情况下, 用in which 引导的定语从句最为正式,用that的次之,而省略了关系代词that 或 in which 的, 反而显得更自然,最为常用.如下面三句话所示,其意义相同. I like the way in which he talks. I like the way that he talks. I like the way he talks. 如果怕弄混淆，下面的可以不看了 另外，在当代美国英语中,the way用作为副词的对格,"the way+从句"实际上相当于一个状语从句来修饰全句. the way=as 1)I'm talking to you just the way I'd talk to a boy of my own. 我和你说话就象和自己孩子说话一样. 2)He did not do it the way his friend did. 他没有象他朋友那样去做此事. 3)Most fruits are naturally sweet and we can eat them just the way they are ----all we have to do is clean or peel them . 大部分水果天然甜润,可以直接食用,我们只需要把他们清洗一下或去皮. the way=according to the way/judging from the way 4)The way you answer the qquestions, you must be an excellent student. 从你回答就知道,你是一个优秀的学生. 5)The way most people look at you, you'd think a trashman was a monster. 从大多数人看你的目光中,你就知道垃圾工在他们眼里是怪物. the way=how/how much 6)I know where you are from by the way you pronounce my name. 从你叫我名字的音调中,我知道你哪里人. 7)No one can imaine the way he misses her. 人们很想想象他是多么想念她. the way=because 8) No wonder that girls looks down upon me, the way you encourage her. 难怪那姑娘看不起我, 原来是你怂恿的