codon usage bias ref: chapter 9 xuhua xia [email protected] http:// dambe.bio.uottawa.ca

Codon usage biasRef: Chapter 9Xuhua [email protected]:// dambe.bio.uottawa.ca

ObjectivesUnderstand how codon usage bias affect translation efficiency and gene expressionBiomedical relevanceProtein drugs in pharmaceutical industryTransgenic experiments in agricultureFactors affecting codon usage biasIndices measuring codon usage biasDevelop bioinformatic skills to study the genomic codon usage.

Codon Usage BiasObservation: Strongly biased codon usage in a variety of species ranging from viruses, mitochondria, plastids, prokaryotes and eukaryotes. Hypotheses:Differential mutation hypothesis, e.g., Transcriptional hypothesis of codon usage (Xia 1996 Genetics 144:1309-1320 )Different selection hypothesis, e.g., (Xia 1998 Genetics 149: 37-44)Predictions:From mutation hypothesis: Concordance between codon usage and mutation pressureFrom Selection hypothesis: Concordance between differential availability of tRNA and differential codon usage.The concordance is stronger in highly expressed genes than lowly expressed genes (CAI is positively correlated with gene expression).

Table 9-2, yeastXia 2007. Bioinformatics and the cell.

AA(1)

Codon(2)

T(3)

w(4)

F(5)

Arg

AGA

11

1

314

Arg

AGG

1

0.091

1

Asn

AAC

10

1

208

Asn

AAU

0

0

11

Asp

GAC

16

1

202

Asp

GAU

0

0

112

Cys

UGC

4

1

3

Cys

UGU

0

0

39

Gln

CAA

9

1

153

Gln

CAG

1

0.111

1

Glu

GAA

14

1

305

Glu

GAG

2

0.143

5

His

CAC

7

1

102

His

CAU

0

0

25

Leu

UUA

7

0.7

42

Leu

UUG

10

1

359

Lys

AAA

7

0.5

65

Lys

AAG

14

1

483

Phe

UUC

10

1

168

Phe

UUU

0

0

19

Ser

AGC

2

1

6

Ser

AGU

0

0

4

Tyr

UAC

8

1

141

Tyr

UAU

0

0

10

Conflict: Initiation and ElongationMet codon usage from the 12 CDSs: AUA214 AUG 37Possible tRNAMet/CAU, tRNAMet/UAUVertebrate mitochondrial genome has only one tRNAMet. Which one to have?tRNAMet/CAU: Good for initiation, but not efficient for AUA codons even with the C modified to 5-formylcytidinetRNAMet/UAU: Good for AUA codons, but not good for initiation.anticodon: CAU favoring the AUG codonNature has chosen CAU: All mitochondrial genomes with a single tRNAMet has a CAU anticodon.Problem with AUA codons in translation?Xia et al. 2007. PLoS One

Hypothesis and PredictionsFavoured by mutation, but not by tRNA-mediated selection because the first (wobble) position in tRNA anticodon is C.Favoured by mutationAlso favoured by tRNA-mediated selection: the first (wobble) position of tRNA is U.Predictions: 1. Proportion of A-ending codons (or RSCU) should be smaller in the Met codon family than in other R-ending codon families:PNNA = NNNA/NNNG2. Availability of tRNAMet/UAU should increase PAUA.

Selection against AUA codonsCarullo, M. and Xia, X. 2008 J Mol Evol 66:484493.

Met

Leu

Glu

Lys

Gln

Arg

Trp

Species

AUA

UUA

GAA

AAA

CAA

AGA

UGA

A. gossypii

1.473

1.993

1.826

1.852

1.917

2

2

C. glabrata

1.043

1.995

2.000

1.938

1.889

2

2

K. thermotolerans

0.556

1.973

1.910

1.948

1.945

2

1.967

S. cerevisiae

1.140

1.969

1.800

1.883

1.794

1.947

1.908

S. castelli

1.299

1.994

1.891

1.981

1.969

2

1.918

S. servazzii

1.321

1.931

1.702

1.824

1.841

1.959

2

Y. lipolytica

1.440

1.968

1.536

1.859

1.963

1.922

1.882

Xia, X. 2012. In: RS Singh et al.. Evolution in the fast lane: Rapidly evolving genes and genetic systems. Oxford University Press.Fig. 5. Relationship between PAUA and PUUA, highlighting the observation that PAUA is greater when both a tRNAMet/CAU and a tRNAMet/UAU are present than when only tRNAMet/CAU is present in the mtDNA, for bivalve species (a) and chordate species (b). The filled squares are for mtDNA containing both tRNAMet/CAU and tRNAMet/UAU genes, and the open triangles are for mtDNA without a tRNAMet/UAU gene.

(a)

(b)

Chart2

56.2865.65

60.3473.96

47.3463.18

46.8964.83

74.0780.18

33.9937.5

58.6660.61

63.8365.02

63.1265.3

PAUA

PAUA

PUUA

PAUA

Bivalve

PUUAPAUAPAUA

Acanthocardia tuberculataNC_008452CAU/CAU65.6556.28

Hiatella arcticaNC_008451CAU/CAU73.9660.34

Crassostrea virginicaNC_007175CAU/CAU63.1847.34

C. gigasNC_001276CAU/CAU64.8346.89

V.philippinarumNC_003354CAU/CAU80.1874.07

Placopecten magellanicusNC_007234CAU/CAU37.533.99

Mytilus trossulusNC_007687CAU/UAU58.6660.61

M. galloprovincialisNC_006886CAU/UAU63.8365.02

M. edulisNC_006161CAU/UAU63.1265.3

PAUAPUUAGroupGXSUMMARY OUTPUT

56.2865.6500

60.3473.9600Regression Statistics

47.3463.1800Multiple R0.9375384846

46.8964.8300R Square0.8789784101

74.0780.1800Adjusted R Square0.8063654561

33.9937.500Standard Error5.3287910681

60.6158.66158.66Observations9

65.0263.83163.83

65.363.12163.12ANOVA

dfSSMSFSignificance F

Regression31031.1996176508343.733205883612.10498075140.0099200083

Residual5141.980071238128.3960142476

Total81173.1796888889

CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

Intercept-2.37010223810.6992462076-0.22152048770.8334500435-29.873390184225.1331857082-29.873390184225.1331857082

PUUA0.86460060580.16313122395.30003138070.0031919730.4452584451.28394276670.4452584451.2839427667

Group8.878155462983.92676456220.10578455530.9198662154-206.8624609657224.6187718914-206.8624609657224.6187718914

GX0.05887248471.35437475060.04346838620.9670106854-3.42265864663.5404036159-3.42265864663.5404036159

SUMMARY OUTPUT

Regression Statistics

Multiple R0.9375140938

R Square0.878932676

Adjusted R Square0.8385769013

Standard Error4.8654175142

Observations9

ANOVA


Regression21031.145963365515.572981682521.77960113830.0017745197

Residual6142.033725523923.6722875873

Total81173.1796888889


Intercept-2.424949719.7007062734-0.24997661420.8109442465-26.161722809321.3118233892-26.161722809321.3118233892

PUUA0.86545470610.1478615145.85314381290.00109802510.50365061581.22725879640.50365061581.2272587964

Group12.5226003773.45782302673.62152726730.0110768964.0616122520.9835885044.0616122520.983588504

Bivalve

00

00

00

00

00

00

00

00

00

PAUA

PAUA

PUUA

PAUA

Tunicates

CodonAAAplidiumConicumNC_013584RSCUCionaIntestinalisNC_004447CionaSavignyiNC_004570ClavelinaLepadiformisNC_012887DiplosomaListerianumNC_013556DoliolumNationalisNC_006627Halocynthia roretziNC_002177HerdmaniaMomusNC_013561MicrocosmusSulcatusNC_013752PhallusiaFumigataNC_009834PhallusiaMammillataNC_009833StyelaPlicataNC_013565

UAG*30.66710.240.88910.2510.28671.55640.66781.610.182101.6676191.5

UAA*61.33391.851.11171.7561.71420.44481.33320.4101.81820.3336130.5

GCUA762.841702.642712.812873.164762.951771.532772.184682.45561.898781.625791.456522

GCGA50.18720.07570.27710.03630.117320.637150.426190.685270.915430.896390.719180.692

GCCA70.262100.37730.11950.18230.117531.05590.25580.28830.102340.708661.217140.538

GCAA190.71240.906200.792170.618210.816390.776401.135160.577321.085370.771330.608200.769

UGUC311.676281.806232321.939391.857220.917731.947341.789361.946331.404190.792421.826

UGCC60.32430.1940010.06130.143261.08320.05340.21110.054140.596291.20840.174

GAUD621.851631.909601.935651.733481.655401.039601.765591.71641.882371.104411.242591.735

GACD50.14930.09120.065100.267100.345370.96180.235100.2940.118300.896250.75890.265

GAGE220.579180.474250.61260.712140.406410.891611.386701.573641.524751.875611.627491.273

GAAE541.421581.526571.39471.288551.594511.109270.614190.427200.47650.125140.373280.727

UUUF4951.8754321.8194601.9095221.8355621.9151671.1254011.9373351.6923611.9361941.3432161.4074041.804

UUCF330.125430.181220.091470.165250.0851300.875130.063610.308120.064950.657910.593440.196

AGAG1331.4382211.7131511.589761.0131641.7921301.088680.872250.685620.681220.463200.519270.551

AGGG520.562370.287390.411740.987190.2081090.912881.128481.3151201.319731.537571.481711.449

GGAG411.763272.038481.811190.644110.978381.246460.722380.425571.06660.595600.57370.841

GGCG40.1720010.03890.30510.08980.26240.063190.21260.112260.234780.741150.341

GGGG160.68880.604140.528180.6140.356351.148610.9571401.564751.3952512.2611871.777410.932

GGUG321.376181.358431.623722.441292.578411.3441442.2591611.799771.4331010.91960.912831.886

CACH70.21260.18540.12370.222110.297310.88660.188160.48550.167290.906321.032120.369

CAUH591.788591.815611.877561.778631.703391.114581.813501.515551.833351.094300.968531.631

AUUI2601.8252961.8852811.9122461.8222811.8861251.2951691.8671241.592331.9581091.4531161.3182261.745

AUCI250.175180.115130.088240.178170.114680.705120.133320.4150.042410.547600.682330.255

AAAK681.4471021.672971.552711.4791281.778501.087280.8260.598420.92350.169250.794310.765

AAGK260.553200.328280.448250.521160.222420.913421.2611.402491.077541.831381.206501.235

CUAL371.345381.505191.07321.113301.5191431.563140.789441.257211.355731.0321021.115481.289

CUCL50.18240.15810.05680.27860.304620.67830.169180.51420.129610.862680.743110.295

CUGL50.18230.11950.28260.20940.203530.579130.732411.17170.452731.032820.896160.43

CUUL632.291562.218462.592692.4391.9751081.18412.31371.057322.065761.0741141.246741.987

UUAL3531.5483981.8513351.5023211.733761.8251301.4212921.2141900.7853551.4261080.8091070.9822521.289

UUGL1030.452320.1491110.498500.27360.175530.5791890.7862941.2151430.5741591.1911111.0181390.711

AUAM1611.4772361.7482131.6141821.6252331.8641421.4131111.314680.7231601.172800.914680.8141161.055

AUGM570.523340.252510.386420.375170.136590.587580.6861201.2771130.828951.086991.1861040.945

AACN120.173160.20140.051150.229290.331601.27750.12190.3880.133280.824250.769190.297

AAUN1271.8271431.7991541.9491161.7711461.669340.723781.88811.621121.867401.176401.2311091.703

CCUP773.02672.577652.708642.783853.119612.103592.408532.232471.899431.737391.405522

CCGP20.07850.192100.41730.1340.147100.345120.4990.379210.848140.566120.432140.538

CCCP70.27540.15440.16740.17430.11180.62140.163160.67490.364170.687461.658120.462

CCAP160.627281.077170.708210.913170.624270.931230.939170.716220.889251.01140.505261

CAGQ100.41750.2120.53380.3410.048281.12211311.216261.13271.459261.333261.156

CAAQ381.583451.8331.467391.66411.952220.88211200.784200.87100.541130.667190.844

CGCR10.08500000020.18230.17450.290000110.815151.09130.267

CGGR90.76640.30850.36430.26100191.101120.696130.945171.388191.407141.01880.711

CGUR262.213251.923221.6282.435292.636191.101291.681292.109141.143161.185201.455171.511

CGAR110.936231.769282.036151.304131.182281.623231.333130.945181.46980.59360.436171.511

AGCS130.27470.175120.235110.17980.186470.90440.063230.33360.1410.774430.945190.304

AGUS821.726731.825901.7651121.821781.814571.0961241.9381151.6671141.9651.226481.0551061.696

UCAS390.746641.169541.009320.634491.077480.97240.78331.008371.035441.006400.842380.826

UCCS140.268150.27460.112120.23880.176501.0150.163130.39750.14581.326551.158280.609

UCGS140.26870.128120.22450.09950.11190.384100.325120.366230.643280.64280.589160.348

UCUS1422.7181332.4291422.6541533.031202.637811.636842.732732.229782.182451.029671.4111022.217

ACAT250.752321381.16310.912431.293330.746331.483250.962351.333150.561210.694240.787

ACCT80.24140.12520.061120.35330.09410.92730.13540.15490.343180.673361.19160.525

ACGT40.1280.25100.30540.11830.09190.42950.225160.615130.495301.121250.826140.459

ACUT962.887842.625812.473892.618842.526841.898482.157592.269481.829441.645391.289682.23

GUGV380.589180.291300.432250.377100.226770.856890.8621331.3071421.3992582.0311631.52960.98

GUUV1161.7981161.8791462.1011422.143902.034911.0111841.7821931.8971551.5271170.9211261.1751841.878

GUCV100.155120.19450.072150.22660.136590.656130.126210.20640.039410.323580.541280.286

GUAV941.4571011.636971.396831.253711.6051331.4781271.23600.591051.034920.724820.765840.857

UGAW601.463701.556691.516481.247581.731581.126440.759230.469390.857310.496200.357200.526

UGGW220.537200.444220.484290.75390.269450.874721.241751.531521.143941.504921.643561.474

UACY180.218160.195110.148250.318270.297901.132150.181330.395100.118630.851731.014420.398

UAUY1471.7821481.8051381.8521321.6821551.703690.8681511.8191341.6051601.882851.149710.9861691.602

PAUA0.73853211010.87407407410.80681818180.81250.9320.70646766170.65680473370.36170212770.58608058610.45714285710.40718562870.5272727273

PUUA0.7741228070.92558139530.75112107620.86522911050.91262135920.71038251370.60706860710.39256198350.71285140560.4044943820.49082568810.6445012788

Lancelet

BranchiostomaBelcheriNC_004537BranchiostomaFloridaeNC_000834BranchiostomaLanceolatumNC_001912EpigonichthysMaldivensisNC_006465

UAG*61.09161.71481.23120.667AplidiumConicumNC_013584.gbAplidiumConicumNC_013584

UAA*50.90910.28650.76941.333BranchiostomaBelcheriNC_004537.gbBranchiostomaBelcheriNC_004537

GCUA1251.7991261.8811211.813981.508BranchiostomaFloridaeNC_000834.gbBranchiostomaFloridaeNC_000834

GCGA440.633340.507350.524490.754BranchiostomaLanceolatumNC_001912.gbBranchiostomaLanceolatumNC_001912

GCCA170.245220.328260.39320.492CionaIntestinalisNC_004447.gbCionaIntestinalisNC_004447

GCAA921.324861.284851.273811.246CionaSavignyiNC_004570.gbCionaSavignyiNC_004570

UGUC331.737231.211231.211281.273ClavelinaLepadiformisNC_012887.gbClavelinaLepadiformisNC_012887

UGCC50.263150.789150.789160.727DiplosomaListerianumNC_013556.gbDiplosomaListerianumNC_013556

GAUD611.564571.425571.425541.521DoliolumNationalisNC_006627.gbDoliolumNationalisNC_006627

GACD170.436230.575230.575170.479EpigonichthysMaldivensisNC_006465.gbEpigonichthysMaldivensisNC_006465

GAGE480.96450.874460.893541.029Halocynthia roretziNC_002177.gbHalocynthia roretziNC_002177

GAAE521.04581.126571.107510.971HerdmaniaMomusNC_013561.gbHerdmaniaMomusNC_013561

UUUF2271.7391701.3491741.3651811.42MicrocosmusSulcatusNC_013752.gbMicrocosmusSulcatusNC_013752

UUCF340.261820.651810.635740.58PhallusiaFumigataNC_009834.gbPhallusiaFumigataNC_009834

GGUG811.095921.26941.288831.118PhallusiaMammillataNC_009833.gbPhallusiaMammillataNC_009833

GGGG1321.7841131.5481111.5211181.589StyelaPlicataNC_013565.gbStyelaPlicataNC_013565

GGCG160.216200.274190.26410.552

GGAG670.905670.918680.932550.741PUUAPAUAPAUA

CACH110.242260.571280.622290.674BranchiostomaBelcheriNC_0045370.71981776770.2918660287CAU

CAUH801.758651.429621.378571.326BranchiostomaFloridaeNC_0008340.72069825440.3134328358CAU

AUUI1991.6381871.6051861.5971591.389BranchiostomaLanceolatumNC_0019120.72681704260.3118811881CAU

AUCI440.362460.395470.403700.611EpigonichthysMaldivensisNC_0064650.7360.3259668508CAU

AAAK431.178401.096401.081371.028AplidiumConicumNC_0135840.7741228070.7385321101CAU/UAU

AAGK300.822330.904340.919350.972CionaIntestinalisNC_0044470.92558139530.8740740741CAU/UAU

CUAL611.488931.683941.686971.644CionaSavignyiNC_0045700.75112107620.8068181818CAU/UAU

CUCL80.195150.271150.269310.525ClavelinaLepadiformisNC_0128870.86522911050.8125CAU/UAU

CUGL190.463360.652410.735510.864DiplosomaListerianumNC_0135560.91262135920.932CAU/UAU

CUUL761.854771.394731.309570.966DoliolumNationalisNC_0066270.71038251370.7064676617CAU/UAU

UUAL3161.442891.4412901.4542761.472Halocynthia roretziNC_0021770.60706860710.6568047337CAU/UAU

UUGL1230.561120.5591090.546990.528HerdmaniaMomusNC_0135610.39256198350.3617021277CAU/UAU

AUGM610.584630.627630.624590.652MicrocosmusSulcatusNC_0137520.71285140560.5860805861CAU/UAU

AUAM1481.4161381.3731391.3761221.348PhallusiaFumigataNC_0098340.4044943820.4571428571CAU/UAU

AACN180.303240.432260.464400.727PhallusiaMammillataNC_0098330.49082568810.4071856287CAU/UAU

AAUN1011.697871.568861.536701.273StyelaPlicataNC_0135650.64450127880.5272727273CAU/UAU

CCUP681.789761.924731.848731.896

CCGP200.526220.557220.557210.545

CCCP190.5200.506240.608180.468

CCAP451.184401.013390.987421.091

CAGQ340.8471.106461.082290.667

CAAQ511.2380.894390.918581.333

CGAR181271.421251.316301.622

CGCR20.111120.632120.63260.324

CGGR301.667211.105221.158191.027

CGUR221.222160.842170.895191.027

AGCS200.578330.895300.808350.959

AGAS290.838120.325120.323310.849

UCAS481.386641.736631.697381.041

UCCS110.318190.515200.539250.685

UCGS220.635170.461190.512190.521

UCUS862.484772.088752.02932.548

AGGS10.029000020.055

AGUS601.733731.98782.101491.342

ACAT691.5651.469651.469651.307

ACCT90.196150.339140.316310.623

ACGT310.674320.723320.723320.643

ACUT751.63651.469661.492711.427

GUCV240.291230.267260.301540.598

GUGV720.873670.779690.8820.909

GUUV1151.3941301.5121271.4721161.285

GUAV1191.4421241.4421231.4261091.208

UGAW621.127581.094601.132520.981

UGGW480.873480.906460.868541.019

UACY340.442530.716540.725600.774

UAUY1201.558951.284951.275951.226

PAUA0.29186602870.31343283580.31188118810.3259668508

PUUA0.71981776770.72069825440.72681704260.736

Lancelet

00

00

00

00

00

00

00

00

00

00

00

00

00

00

00

00

PAUA

PAUA

PUUA

PAUA

Chart3

0.29186602870.7198177677

0.31343283580.7206982544

0.31188118810.7268170426

0.32596685080.736

0.7741228070.7385321101

0.92558139530.8740740741

0.75112107620.8068181818

0.86522911050.8125

0.91262135920.932

0.71038251370.7064676617

0.60706860710.6568047337

0.39256198350.3617021277

0.71285140560.5860805861

0.4044943820.4571428571

0.49082568810.4071856287

0.64450127880.5272727273

PAUA

PAUA

PUUA

PAUA

Bivalve

PUUAPAUAPAUA

Acanthocardia tuberculataNC_008452CAU/CAU65.6556.28

Hiatella arcticaNC_008451CAU/CAU73.9660.34

Crassostrea virginicaNC_007175CAU/CAU63.1847.34

C. gigasNC_001276CAU/CAU64.8346.89

V.philippinarumNC_003354CAU/CAU80.1874.07

Placopecten magellanicusNC_007234CAU/CAU37.533.99

Mytilus trossulusNC_007687CAU/UAU58.6660.61

M. galloprovincialisNC_006886CAU/UAU63.8365.02

M. edulisNC_006161CAU/UAU63.1265.3

PAUAPUUAGroupGXSUMMARY OUTPUT

56.2865.6500

60.3473.9600Regression Statistics

47.3463.1800Multiple R0.9375384846

46.8964.8300R Square0.8789784101

74.0780.1800Adjusted R Square0.8063654561

33.9937.500Standard Error5.3287910681

60.6158.66158.66Observations9

65.0263.83163.83

65.363.12163.12ANOVA


Regression31031.1996176508343.733205883612.10498075140.0099200083

Residual5141.980071238128.3960142476

Total81173.1796888889


Intercept-2.37010223810.6992462076-0.22152048770.8334500435-29.873390184225.1331857082-29.873390184225.1331857082

PUUA0.86460060580.16313122395.30003138070.0031919730.4452584451.28394276670.4452584451.2839427667

Group8.878155462983.92676456220.10578455530.9198662154-206.8624609657224.6187718914-206.8624609657224.6187718914

GX0.05887248471.35437475060.04346838620.9670106854-3.42265864663.5404036159-3.42265864663.5404036159

SUMMARY OUTPUT

Regression Statistics

Multiple R0.9375140938

R Square0.878932676

Adjusted R Square0.8385769013

Standard Error4.8654175142

Observations9

ANOVA


Regression21031.145963365515.572981682521.77960113830.0017745197

Residual6142.033725523923.6722875873

Total81173.1796888889


Intercept-2.424949719.7007062734-0.24997661420.8109442465-26.161722809321.3118233892-26.161722809321.3118233892

PUUA0.86545470610.1478615145.85314381290.00109802510.50365061581.22725879640.50365061581.2272587964

Group12.5226003773.45782302673.62152726730.0110768964.0616122520.9835885044.0616122520.983588504

Bivalve

00

00

00

00

00

00

00

00

00

PAUA

PAUA

PUUA

PAUA

Tunicates

CodonAAAplidiumConicumNC_013584RSCUCionaIntestinalisNC_004447CionaSavignyiNC_004570ClavelinaLepadiformisNC_012887DiplosomaListerianumNC_013556DoliolumNationalisNC_006627Halocynthia roretziNC_002177HerdmaniaMomusNC_013561MicrocosmusSulcatusNC_013752PhallusiaFumigataNC_009834PhallusiaMammillataNC_009833StyelaPlicataNC_013565

UAG*30.66710.240.88910.2510.28671.55640.66781.610.182101.6676191.5

UAA*61.33391.851.11171.7561.71420.44481.33320.4101.81820.3336130.5

GCUA762.841702.642712.812873.164762.951771.532772.184682.45561.898781.625791.456522

GCGA50.18720.07570.27710.03630.117320.637150.426190.685270.915430.896390.719180.692

GCCA70.262100.37730.11950.18230.117531.05590.25580.28830.102340.708661.217140.538

GCAA190.71240.906200.792170.618210.816390.776401.135160.577321.085370.771330.608200.769

UGUC311.676281.806232321.939391.857220.917731.947341.789361.946331.404190.792421.826

UGCC60.32430.1940010.06130.143261.08320.05340.21110.054140.596291.20840.174

GAUD621.851631.909601.935651.733481.655401.039601.765591.71641.882371.104411.242591.735

GACD50.14930.09120.065100.267100.345370.96180.235100.2940.118300.896250.75890.265

GAGE220.579180.474250.61260.712140.406410.891611.386701.573641.524751.875611.627491.273

GAAE541.421581.526571.39471.288551.594511.109270.614190.427200.47650.125140.373280.727

UUUF4951.8754321.8194601.9095221.8355621.9151671.1254011.9373351.6923611.9361941.3432161.4074041.804

UUCF330.125430.181220.091470.165250.0851300.875130.063610.308120.064950.657910.593440.196

AGAG1331.4382211.7131511.589761.0131641.7921301.088680.872250.685620.681220.463200.519270.551

AGGG520.562370.287390.411740.987190.2081090.912881.128481.3151201.319731.537571.481711.449

GGAG411.763272.038481.811190.644110.978381.246460.722380.425571.06660.595600.57370.841

GGCG40.1720010.03890.30510.08980.26240.063190.21260.112260.234780.741150.341

GGGG160.68880.604140.528180.6140.356351.148610.9571401.564751.3952512.2611871.777410.932

GGUG321.376181.358431.623722.441292.578411.3441442.2591611.799771.4331010.91960.912831.886

CACH70.21260.18540.12370.222110.297310.88660.188160.48550.167290.906321.032120.369

CAUH591.788591.815611.877561.778631.703391.114581.813501.515551.833351.094300.968531.631

AUUI2601.8252961.8852811.9122461.8222811.8861251.2951691.8671241.592331.9581091.4531161.3182261.745

AUCI250.175180.115130.088240.178170.114680.705120.133320.4150.042410.547600.682330.255

AAAK681.4471021.672971.552711.4791281.778501.087280.8260.598420.92350.169250.794310.765

AAGK260.553200.328280.448250.521160.222420.913421.2611.402491.077541.831381.206501.235

CUAL371.345381.505191.07321.113301.5191431.563140.789441.257211.355731.0321021.115481.289

CUCL50.18240.15810.05680.27860.304620.67830.169180.51420.129610.862680.743110.295

CUGL50.18230.11950.28260.20940.203530.579130.732411.17170.452731.032820.896160.43

CUUL632.291562.218462.592692.4391.9751081.18412.31371.057322.065761.0741141.246741.987

UUAL3531.5483981.8513351.5023211.733761.8251301.4212921.2141900.7853551.4261080.8091070.9822521.289

UUGL1030.452320.1491110.498500.27360.175530.5791890.7862941.2151430.5741591.1911111.0181390.711

AUAM1611.4772361.7482131.6141821.6252331.8641421.4131111.314680.7231601.172800.914680.8141161.055

AUGM570.523340.252510.386420.375170.136590.587580.6861201.2771130.828951.086991.1861040.945

AACN120.173160.20140.051150.229290.331601.27750.12190.3880.133280.824250.769190.297

AAUN1271.8271431.7991541.9491161.7711461.669340.723781.88811.621121.867401.176401.2311091.703

CCUP773.02672.577652.708642.783853.119612.103592.408532.232471.899431.737391.405522

CCGP20.07850.192100.41730.1340.147100.345120.4990.379210.848140.566120.432140.538

CCCP70.27540.15440.16740.17430.11180.62140.163160.67490.364170.687461.658120.462

CCAP160.627281.077170.708210.913170.624270.931230.939170.716220.889251.01140.505261

CAGQ100.41750.2120.53380.3410.048281.12211311.216261.13271.459261.333261.156

CAAQ381.583451.8331.467391.66411.952220.88211200.784200.87100.541130.667190.844

CGCR10.08500000020.18230.17450.290000110.815151.09130.267

CGGR90.76640.30850.36430.26100191.101120.696130.945171.388191.407141.01880.711

CGUR262.213251.923221.6282.435292.636191.101291.681292.109141.143161.185201.455171.511

CGAR110.936231.769282.036151.304131.182281.623231.333130.945181.46980.59360.436171.511

AGCS130.27470.175120.235110.17980.186470.90440.063230.33360.1410.774430.945190.304

AGUS821.726731.825901.7651121.821781.814571.0961241.9381151.6671141.9651.226481.0551061.696

UCAS390.746641.169541.009320.634491.077480.97240.78331.008371.035441.006400.842380.826

UCCS140.268150.27460.112120.23880.176501.0150.163130.39750.14581.326551.158280.609

UCGS140.26870.128120.22450.09950.11190.384100.325120.366230.643280.64280.589160.348

UCUS1422.7181332.4291422.6541533.031202.637811.636842.732732.229782.182451.029671.4111022.217

ACAT250.752321381.16310.912431.293330.746331.483250.962351.333150.561210.694240.787

ACCT80.24140.12520.061120.35330.09410.92730.13540.15490.343180.673361.19160.525

ACGT40.1280.25100.30540.11830.09190.42950.225160.615130.495301.121250.826140.459

ACUT962.887842.625812.473892.618842.526841.898482.157592.269481.829441.645391.289682.23

GUGV380.589180.291300.432250.377100.226770.856890.8621331.3071421.3992582.0311631.52960.98

GUUV1161.7981161.8791462.1011422.143902.034911.0111841.7821931.8971551.5271170.9211261.1751841.878

GUCV100.155120.19450.072150.22660.136590.656130.126210.20640.039410.323580.541280.286

GUAV941.4571011.636971.396831.253711.6051331.4781271.23600.591051.034920.724820.765840.857

UGAW601.463701.556691.516481.247581.731581.126440.759230.469390.857310.496200.357200.526

UGGW220.537200.444220.484290.75390.269450.874721.241751.531521.143941.504921.643561.474

UACY180.218160.195110.148250.318270.297901.132150.181330.395100.118630.851731.014420.398

UAUY1471.7821481.8051381.8521321.6821551.703690.8681511.8191341.6051601.882851.149710.9861691.602

PAUA0.73853211010.87407407410.80681818180.81250.9320.70646766170.65680473370.36170212770.58608058610.45714285710.40718562870.5272727273

PUUA0.7741228070.92558139530.75112107620.86522911050.91262135920.71038251370.60706860710.39256198350.71285140560.4044943820.49082568810.6445012788

Lancelet

BranchiostomaBelcheriNC_004537BranchiostomaFloridaeNC_000834BranchiostomaLanceolatumNC_001912EpigonichthysMaldivensisNC_006465

UAG*61.09161.71481.23120.667AplidiumConicumNC_013584.gbAplidiumConicumNC_013584

UAA*50.90910.28650.76941.333BranchiostomaBelcheriNC_004537.gbBranchiostomaBelcheriNC_004537

GCUA1251.7991261.8811211.813981.508BranchiostomaFloridaeNC_000834.gbBranchiostomaFloridaeNC_000834

GCGA440.633340.507350.524490.754BranchiostomaLanceolatumNC_001912.gbBranchiostomaLanceolatumNC_001912

GCCA170.245220.328260.39320.492CionaIntestinalisNC_004447.gbCionaIntestinalisNC_004447

GCAA921.324861.284851.273811.246CionaSavignyiNC_004570.gbCionaSavignyiNC_004570

UGUC331.737231.211231.211281.273ClavelinaLepadiformisNC_012887.gbClavelinaLepadiformisNC_012887

UGCC50.263150.789150.789160.727DiplosomaListerianumNC_013556.gbDiplosomaListerianumNC_013556

GAUD611.564571.425571.425541.521DoliolumNationalisNC_006627.gbDoliolumNationalisNC_006627

GACD170.436230.575230.575170.479EpigonichthysMaldivensisNC_006465.gbEpigonichthysMaldivensisNC_006465

GAGE480.96450.874460.893541.029Halocynthia roretziNC_002177.gbHalocynthia roretziNC_002177

GAAE521.04581.126571.107510.971HerdmaniaMomusNC_013561.gbHerdmaniaMomusNC_013561

UUUF2271.7391701.3491741.3651811.42MicrocosmusSulcatusNC_013752.gbMicrocosmusSulcatusNC_013752

UUCF340.261820.651810.635740.58PhallusiaFumigataNC_009834.gbPhallusiaFumigataNC_009834

GGUG811.095921.26941.288831.118PhallusiaMammillataNC_009833.gbPhallusiaMammillataNC_009833

GGGG1321.7841131.5481111.5211181.589StyelaPlicataNC_013565.gbStyelaPlicataNC_013565

GGCG160.216200.274190.26410.552

GGAG670.905670.918680.932550.741PUUAPAUAPAUA

CACH110.242260.571280.622290.674BranchiostomaBelcheriNC_0045370.71981776770.2918660287CAU

CAUH801.758651.429621.378571.326BranchiostomaFloridaeNC_0008340.72069825440.3134328358CAU

AUUI1991.6381871.6051861.5971591.389BranchiostomaLanceolatumNC_0019120.72681704260.3118811881CAU

AUCI440.362460.395470.403700.611EpigonichthysMaldivensisNC_0064650.7360.3259668508CAU

AAAK431.178401.096401.081371.028AplidiumConicumNC_0135840.7741228070.7385321101CAU/UAU

AAGK300.822330.904340.919350.972CionaIntestinalisNC_0044470.92558139530.8740740741CAU/UAU

CUAL611.488931.683941.686971.644CionaSavignyiNC_0045700.75112107620.8068181818CAU/UAU

CUCL80.195150.271150.269310.525ClavelinaLepadiformisNC_0128870.86522911050.8125CAU/UAU

CUGL190.463360.652410.735510.864DiplosomaListerianumNC_0135560.91262135920.932CAU/UAU

CUUL761.854771.394731.309570.966DoliolumNationalisNC_0066270.71038251370.7064676617CAU/UAU

UUAL3161.442891.4412901.4542761.472Halocynthia roretziNC_0021770.60706860710.6568047337CAU/UAU

UUGL1230.561120.5591090.546990.528HerdmaniaMomusNC_0135610.39256198350.3617021277CAU/UAU

AUGM610.584630.627630.624590.652MicrocosmusSulcatusNC_0137520.71285140560.5860805861CAU/UAU

AUAM1481.4161381.3731391.3761221.348PhallusiaFumigataNC_0098340.4044943820.4571428571CAU/UAU

AACN180.303240.432260.464400.727PhallusiaMammillataNC_0098330.49082568810.4071856287CAU/UAU

AAUN1011.697871.568861.536701.273StyelaPlicataNC_0135650.64450127880.5272727273CAU/UAU

CCUP681.789761.924731.848731.896

CCGP200.526220.557220.557210.545

CCCP190.5200.506240.608180.468

CCAP451.184401.013390.987421.091

CAGQ340.8471.106461.082290.667

CAAQ511.2380.894390.918581.333

CGAR181271.421251.316301.622

CGCR20.111120.632120.63260.324

CGGR301.667211.105221.158191.027

CGUR221.222160.842170.895191.027

AGCS200.578330.895300.808350.959

AGAS290.838120.325120.323310.849

UCAS481.386641.736631.697381.041

UCCS110.318190.515200.539250.685

UCGS220.635170.461190.512190.521

UCUS862.484772.088752.02932.548

AGGS10.029000020.055

AGUS601.733731.98782.101491.342

ACAT691.5651.469651.469651.307

ACCT90.196150.339140.316310.623

ACGT310.674320.723320.723320.643

ACUT751.63651.469661.492711.427

GUCV240.291230.267260.301540.598

GUGV720.873670.779690.8820.909

GUUV1151.3941301.5121271.4721161.285

GUAV1191.4421241.4421231.4261091.208

UGAW621.127581.094601.132520.981

UGGW480.873480.906460.868541.019

UACY340.442530.716540.725600.774

UAUY1201.558951.284951.275951.226

PAUA0.29186602870.31343283580.31188118810.3259668508

PUUA0.71981776770.72069825440.72681704260.736

Lancelet

00

00

00

00

00

00

00

00

00

00

00

00

00

00

00

00

PAUA

PAUA

PUUA

PAUA

Calculation of RSCURSCU is codon-specificRSCU and proportion: Different scaling.

Sheet1

CodonAANRSCUCodonAANRSCUCodonAANRSCU

GCUAla520.84CCUPro420.87UAA*83.2

GCCAla911.47CCCPro631.31UAG*10.4

GCAAla1031.66CCAPro851.76AGA*10.4

GCGAla20.03CCGPro30.06AGG*00

GAAGlu781.64CAAGln791.82AAALys901.78

GAGGlu170.36CAGGln80.18AAGLys110.22

GGUGly290.53CGUArg70.44ACUThr440.57

GGCGly621.13CGCArg110.7ACCThr961.25

GGAGly971.77CGAArg422.67ACAThr1531.99

GGGGly310.57CGGArg30.19ACGThr150.19

UUALeu1101.11AUAMet2181.66UGATrp921.77

UUGLeu160.16AUGMet440.34UGGTrp120.23

CUULeu620.62UCUSer511.11GUUVal400.84

CUCLeu950.95UCCSer651.42GUCVal481.01

CUALeu2852.86UCASer992.16GUAVal871.83

CUGLeu290.29UCGSer50.11GUGVal150.32

Sheet2

Sheet3

Calculation of CAICompound 6- or 8-fold codon families should be broken into two codon families CAI is gene-specific. 0 CAI 1CAI computed with different reference sets are not comparable. Problem with computing w as Fi/Fi.max: Suppose an amino acid is rarely used in highly expressed genes, then there is little selection on it, and the codon usage might be close to even, with wi 1. Now if we have a lowly expressed gene that happen to be made of entire of this amino acid, then the CAI for this lowly expressed gene would be 1, which is misleading.There has been no good alternative. Further research is needed.N2,3,4: Number of 2-, 3-, 4-fold codon families

Sheet1

AAAK1855UGA*00.388

AACN1434UAG*00.243

AAGK2464UAA*01

AATN1646GCAA10.606

ACAT1067GCUA151

ACCT1056GCGA00.253

ACGT478GCCA80.75

ACTT1122UGCC31

AGAR950UGUC30.909

AGCS463GAUD91

AGGR187GACD110.581

AGTS623GAGE110.862

ATAI340GAAE151

ATCI1574UUUF40.552

ATGM1739UUCF91

ATTI1666GGAG111

CAAQ2106GGUG140.248

CACH751GGGG00.06

CAGQ966GGCG50.136

CATH910CACH50.825

CCAP2617CAUH21

CCCP222AUCI120.945

CCGP521AUUI111

CCTP461AUAI00.204

CGAR698AAGK271

CGCR525AAAK50.753

CGGR216UUAL00.265

CGTR1115UUGL120.74

CTAL274CUAL00.181

CTCL1244CUCL20.822

CTGL591CUGL40.39

CTTL1514CUUL41

GAAE2523AUGM101

GACD1416AAUN21

GAGE2175AACN140.871

GATD2437CCGP20.199

GCAA1107CCUP70.176

GCCA1371CCAP71

GCGA463CCCP90.085

GCTA1827CAGQ50.459

GGAG3372CAAQ21

GGCG460CGGR10.194

GGGG204CGCR10.471

GGTG837CGAR10.626

GTAV497AGAR40.852

GTCV1239AGGR20.168

GTGV725CGUR61

GTTV1645AGUS20.529

TAA*103AGCS30.393

TACY1129UCUS30.856

TAG*25UCGS30.621

TATY949UCAS01

TCAS1177UCCS50.764

TCCS899ACAT20.951

TCGS731ACCT140.941

TCTS1007ACGT00.426

TGA*40ACUT121

TGCC738GUGV60.441

TGGW686GUCV150.753

TGTC671GUAV30.302

TTAL401GUUV71

TTCF1640UGGW41

TTGL1120UAUY10.841

TTTF906UACY81

Sheet2

AAAK1855UGA*00.388CodonAAObsFreqRefCodFreqw

AACN1434UAG*00.243UGA*060.375

AAGK2464UAA*01UAG*040.250

AATN1646GCAA10.606UAA*0161.000

ACAT1067GCUA151GCAA11950.606

ACCT1056GCGA00.253GCUA153221.000

ACGT478GCCA80.75GCGA0810.252

ACTT1122UGCC31GCCA82420.752

AGAR950UGUC30.909UGCC31231.000

AGCS463GAUD91UGUC31120.911

AGGR187GACD110.581GAUD9691.000

AGTS623GAGE110.862GACD11400.580

ATAI340GAAE151GAGE112890.863

ATCI1574UUUF40.552GAAE143351.000

ATGM1739UUCF91UUUF31180.554

ATTI1666GGAG111UUCF92131.000

CAAQ2106GGUG140.248

CACH751GGGG00.06

CAGQ966GGCG50.136

CATH910CACH50.825

CCAP2617CAUH21

CCCP222AUCI120.945

CCGP521AUUI111

CCTP461AUAI00.204

CGAR698AAGK271

CGCR525AAAK50.753

CGGR216UUAL00.265

CGTR1115UUGL120.74

CTAL274CUAL00.181

CTCL1244CUCL20.822

CTGL591CUGL40.39

CTTL1514CUUL41

GAAE2523AUGM101

GACD1416AAUN21

GAGE2175AACN140.871

GATD2437CCGP20.199

GCAA1107CCUP70.176

GCCA1371CCAP71

GCGA463CCCP90.085

GCTA1827CAGQ50.459

GGAG3372CAAQ21

GGCG460CGGR10.194

GGGG204CGCR10.471

GGTG837CGAR10.626

GTAV497AGAR40.852

GTCV1239AGGR20.168

GTGV725CGUR61

GTTV1645AGUS20.529

TAA*103AGCS30.393

TACY1129UCUS30.856

TAG*25UCGS30.621

TATY949UCAS01

TCAS1177UCCS50.764

TCCS899ACAT20.951

TCGS731ACCT140.941

TCTS1007ACGT00.426

TGA*40ACUT121

TGCC738GUGV60.441

TGGW686GUCV150.753

TGTC671GUAV30.302

TTAL401GUUV71

TTCF1640UGGW41

TTGL1120UAUY10.841

TTTF906UACY81

Sheet3

520.8387096774

911.4677419355

1031.6612903226

20.0322580645

248

MBD0002DDBE.xls

Sheet1

CodonAANRSCRCodonAANRSCRCodonAANRSCR

GCUAla520.84CCUPro420.87UAA*83.2

GCCAla911.47CCCPro631.31UAG*10.4

GCAAla1031.66CCAPro851.76AGA*10.4

GCGAla20.03CCGPro30.06AGG*00

GAAGlu781.64CAAGln791.82AAALys901.78

GAGGlu170.36CAGGln80.18AAGLys110.22

GGUGly290.53CGUArg70.44ACUThr440.57

GGCGly621.13CGCArg110.7ACCThr961.25

GGAGly971.77CGAArg422.67ACAThr1531.99

GGGGly310.57CGGArg30.19ACGThr150.19

UUALeu1101.11AUAMet2181.66UGATrp921.77

UUGLeu160.16AUGMet440.34UGGTrp120.23

CUULeu620.62UCUSer511.11GUUVal400.84

CUCLeu950.95UCCSer651.42GUCVal481.01

CUALeu2852.86UCASer992.16GUAVal871.83

CUGLeu290.29UCGSer50.11GUGVal150.32

Sheet2

Sheet3

Weak mRNA predictive powerFRS2ENO1

Effect of Codon Usage BiasFRS2ENO1

Problems with CAIFormulationReference setw = 0ImplementationAUGUGGMultiple codon families for one amino acidDependence on AT%Solutions (Xia, X. 2007. Evolutionary Bioinformatics)

RSCU (HIV-1 vs Human)Fig. 1. Relative synonymous codon usage (RSCU) of HIV-1 compared to RSCU of highly expressed human genes. Data points for codons ending with A, C, G or U are annotated with different combinations of colors and symbols. A-ending codons exhibit strong discordance in their usage between HIV-1 and human and are annotated with their coded amino acids. van Weringh et al. 2011. MBE.

ResearchObservation on HIV-1: Strong surplus of A-ending codonHigh mutation rateHypothesis: Strong A-biased mutation disrupting codon adaptation.Prediction: Strong A-biased mutation (confirmed)If mutation rate is lower, then there will be better codon adaptation (The related HTLV-1 parasitizes the same cell as HIV-1, but have lower mutation rate: HTLV-1 genes should exhibit better codon adaptation)

RSCU (HTLV-1 vs Human)Relative synonymous codon usage (RSCU) of HTLV-1 compared to RSCU of highly expressed human genes. Data points for codons ending with A, C, G or U are annotated with different combinations of colors and symbols. A-ending codons exhibit strong discordance in their usage between HIV-1 and human and are annotated with their coded amino acids.

Chart1

0.510.74202898550.74202898550.7420289855

1.2240.78346028290.78346028290.7834602829

1.180.92817679560.92817679560.9281767956

0.7970.35839160840.35839160840.3583916084

1.50.76137339060.76137339060.7613733906

1.0730.29585087190.29585087190.2958508719

1.5050.67714285710.67714285710.6771428571

0.9860.93228655540.93228655540.9322865554

0.9450.51993262210.51993262210.5199326221

0.7880.97315436240.97315436240.9731543624

0.9320.75247524750.75247524750.7524752475

0.8150.79188900750.79188900750.7918890075

0.8210.97052541650.97052541650.9705254165

0.5830.38819875780.38819875780.3881987578

1.74057971012.4381.74057971011.7405797101

1.20276953511.4351.20276953511.2027695351

1.17019230771.2341.17019230771.1701923077

1.19561454131.0731.19561454131.1956145413

1.5453827941.281.5453827941.545382794

1.18640576731.2281.18640576731.1864057673

1.69055944061.2191.69055944061.6905594406

1.06674684311.4041.06674684311.0667468431

1.16544117651.1081.16544117651.1654411765

1.46418056921.7291.46418056921.4641805692

1.60936093611.2331.60936093611.6093609361

1.40476190481.2811.40476190481.4047619048

1.60939167562.2221.60939167561.6093916756

1.7291755661.9321.7291755661.729175566

1.01397515531.751.01397515531.0139751553

1.19484702091.3071.19484702091.1948470209

0.34347826090.34347826090.3030.3434782609

1.21653971711.21653971710.7761.2165397171

0.87134964480.87134964481.060.8713496448

1.23862660941.23862660940.51.2386266094

2.11906193632.11906193630.5812.1190619363

1.32285714291.32285714290.4951.3228571429

0.47301275760.47301275760.4250.4730127576

1.48006737791.48006737791.0551.4800673779

1.02684563761.02684563761.2121.0268456376

1.11611161121.11611161121.0531.1161116112

0.36926360730.36926360730.1480.3692636073

0.37761640320.37761640320.2560.3776164032

1.93478260871.93478260870.8611.9347826087

1.17391304351.17391304351.17391304350.749

0.79723046490.79723046490.79723046490.565

0.82980769230.82980769230.82980769230.766

0.80438545870.80438545870.80438545870.927

0.65509076560.65509076560.65509076560.48

0.81359423270.81359423270.81359423270.772

0.9510489510.9510489510.9510489510.984

0.51834034880.51834034880.51834034880.942

0.83455882350.83455882350.83455882350.892

1.13052011781.13052011781.13052011780.86

0.52205220520.52205220520.52205220520.782

0.59523809520.59523809520.59523809520.719

1.22945570971.22945570971.22945570970.815

0.92268261430.92268261430.92268261430.991

0.66304347830.66304347830.66304347830.806

0.80515297910.80515297910.80515297910.693

A-ending

C-ending

G-ending

U-ending

RSCU (Human)

RSCU (HTLV-1)

Fig2A

--AverageError--AverageErrorArg(AGA)

--HIV WTHIV WT--HIV MUTHIV MUTArg(AGG)

Ile-UAU1.339670.70913Ile-UAU0.061390.022161.88917405842.7703068592Ile(AUA)

Lys1,21.008130.29927Lys1,20.060080.017493.36863033383.4351057747Ile(AUY)

Lys30.640520.25086Lys30.033952.02E-042.5532966595167.9196755367Leu(UUA)

Asn-GUU0.458820.12913Asn-GUU0.041770.00469Leu(UUG)

Sec-UCA10.269970.19873Sec-UCA10.02978.58E-04Lys(AAA)

Ile-IAU/GAU0.267240.08196Ile-IAU/GAU0.137110.050753.26061493412.7016748768Lys(AAG)

His-GUG0.209870.0246His-GUG0.102210.04699Gly(GGA)

Gly-GCC/CCC0.201640.08479Gly-GCC/CCC0.048590.010462.37811062634.6453154876Gly(GGB)

Pro-IGG/CGG/UGG0.194840.11125Pro-IGG/CGG/UGG0.055520.03084Val(GUA)

Thr-IGU/CGU0.190040.09363Thr-IGU/CGU0.015490.00784Val(GUB)

Met-CAU0.184240.03201Met-CAU0.041640.00719Thr(ACA)

Arg-CCG/UCG0.171890.00734Arg-CCG/UCG0.042140.00163Thr(ACB)

Glu-CUC/UUC0.157570.01142Glu-CUC/UUC0.048960.01635

Arg-ICG0.13350.02488Arg-ICG0.048020.00623

Asp-GUC0.130290.03841Asp-GUC0.057370.01104

Ala-IGC/CGC/UGC0.113210.01105Ala-IGC/CGC/UGC0.073770.03882

Ala-CGC0.099250.01093Ala-CGC0.06940.0283

Leu-UAA0.090.03616Leu-UAA0.037380.008112.48893805314.6091245376

Cys-GCA0.082810.02926Cys-GCA0.026610.00898

Leu-IAG/UAG0.079650.04071Leu-IAG/UAG0.041780.01059

Sec-UCA20.078830.01611Sec-UCA20.060110.02047

Val-IAC/CAC0.073870.0285Val-IAC/CAC0.048530.021182.59192982462.291312559

Gly-UCC0.070750.05595Gly-UCC0.028950.006171.26452189454.6920583468

Tyr-GUA0.068330.01475Tyr-GUA0.03620.01522

Val-UAC0.066170.02318Val-UAC0.028230.01322.85461604832.1386363636

Arg-CCU0.0660.03084Arg-CCU0.054380.022582.1400778212.4083259522

Thr-CGU0.062150.0152Thr-CGU0.019210.006794.08881578952.8291605302

Ser-GCU0.060460.03637Ser-GCU0.019630.00788

Gln-CUG/UUG0.058650.00177Gln-CUG/UUG0.021390.00217

Glu-UUC0.054240.01134Glu-UUC0.019180.00184

Ser-CGA0.05150.02118Ser-CGA0.022440.01514

Arg-UCU0.049420.00253Arg-UCU0.027670.0021819.533596837912.6926605505

Thr-UGU0.048140.00106Thr-UGU0.021480.007245.41509433962.9833333333

Phe-GAA0.046840.00865Phe-GAA0.017510.00531

Leu-CAA0.045040.015Leu-CAA0.049560.025033.00266666671.9800239712

Trp-CCA0.035750.00952Trp-CCA0.018460.0082

Leu-CAG0.031960.01431Leu-CAG0.021570.01228

Met-i0.026230.00355Met-i0.01610.00704

Ser-IGA/UGA0.016610.00137Ser-IGA/UGA0.010610.00118

Leu-UAA20.00780.0069Leu-UAA20.015430.00306

----------

mGln0.030420.01646mGln0.024780.01961

mGlu0.027030.00706mGlu0.022080.00217

mAsp0.026590.01066mAsp0.027750.01513

mPro0.021320.01909mPro0.017370.01656

mPhe0.01940.00432mPhe0.019640.01056

mVal0.018480.01059mVal0.013240.01119

mMet0.0180.00455mMet0.014660.00276

mAsn0.017520.01484mAsn0.013560.01279

mHis0.015730.0025mHis0.009070.00417

mArg0.015480.00258mArg0.018810.00967

mLeu-UAA0.014480.00168mLeu-UAA0.011340.00185

mSer-GCU0.013010.00997mSer-GCU0.032180.01353

mLys0.012971.82E-04mLys0.009640.00171

mIle0.011240.01005mIle0.009550.00536

mTyr0.00990.00729mTyr0.010460.00579

mSer-UGA0.008550.00753mSer-UGA0.007530.00519

mAla0.008450.00634mAla0.00890.0041

mThr0.008290.0069mThr0.007680.00573

mLeu-UAG0.007640.0068mLeu-UAG0.00610.00542

mTrp0.006070.00397mTrp0.004850.00343

mGly0.005640.00434mGly0.004560.00349

mCys0.004510.00403mCys0.003710.00317

----

Fig2B

--AverageError

--HIV MUTHIV MUT

Ile-UAU0.061390.02216

Lys1,20.060080.01749

Lys30.033952.02E-04

Asn-GUU0.041770.00469

Sec-UCA10.02978.58E-04

Ile-IAU/GAU0.137110.05075

His-GUG0.102210.04699

Gly-GCC/CCC0.048590.01046

Pro-IGG/CGG/UGG0.055520.03084

Thr-IGU/CGU0.015490.00784

Met-CAU0.041640.00719

Arg-CCG/UCG0.042140.00163

Glu-CUC/UUC0.048960.01635

Arg-ICG0.048020.00623

Asp-GUC0.057370.01104

Ala-IGC/CGC/UGC0.073770.03882

Ala-CGC0.06940.0283

Leu-UAA0.037380.00811

Cys-GCA0.026610.00898

Leu-IAG/UAG0.041780.01059

Sec-UCA20.060110.02047

Val-IAC/CAC0.048530.02118

Gly-UCC0.028950.00617

Tyr-GUA0.03620.01522

Val-UAC0.028230.0132

Arg-CCU0.054380.02258

Thr-CGU0.019210.00679

Ser-GCU0.019630.00788

Gln-CUG/UUG0.021390.00217

Glu-UUC0.019180.00184

Ser-CGA0.022440.01514

Arg-UCU0.027670.00218

Thr-UGU0.021480.0072

Phe-GAA0.017510.00531

Leu-CAA0.049560.02503

Trp-CCA0.018460.0082

Leu-CAG0.021570.01228

Met-i0.01610.00704

Ser-IGA/UGA0.010610.00118

Leu-UAA20.015430.00306

------

mGln0.024780.01961

mGlu0.022080.00217

mAsp0.027750.01513

mPro0.017370.01656

mPhe0.019640.01056

mVal0.013240.01119

mMet0.014660.00276

mAsn0.013560.01279

mHis0.009070.00417

mArg0.018810.00967

mLeu-UAA0.011340.00185

mSer-GCU0.032180.01353

mLys0.009640.00171

mIle0.009550.00536

mTyr0.010460.00579

mSer-UGA0.007530.00519

mAla0.00890.0041

mThr0.007680.00573

mLeu-UAG0.00610.00542

mTrp0.004850.00343

mGly0.004560.00349

mCys0.003710.00317

--

Fig3A

--AverageErroraverageerror

--293T293THIV WTHIV WTlogRatio

Lys32.727370.861517.732910.22252.701

Lys1,21.772370.3779416.891671.517263.253

Asn-GUU3.379360.9394110.624751.435411.653

Glu-CUC/UUC4.980350.154254.208870.1755-0.243

Pro-IGG/CGG/UGG6.221192.608614.164570.61297-0.579

Ile-UAU0.625490.093814.11520.090092.718

Thr-IGU/CGU4.258170.429063.974360.66775-0.100

Gly-GCC/CCC2.119070.106552.699340.109310.349

Asp-GUC4.002340.30412.615540.97891-0.614

Arg-CCG/UCG2.666220.723152.544680.0461-0.067

Met-CAU1.501090.072892.118140.672720.497

Gly-UCC3.42040.354741.86260.87535-0.877

His-GUG0.874940.087051.812620.850641.051

Cys-GCA2.775990.029421.753370.67296-0.663

Arg-ICG2.679020.695931.615640.14948-0.730

Glu-UUC5.990950.969791.491130.22708-2.006

Tyr-GUA4.600010.388831.433040.22857-1.683

Gln-CUG/UUG4.280.020431.393620.06732-1.619

Ile-IAU/GAU0.581020.046731.371280.437861.239

Val-IAC/CAC2.169470.286911.29550.35448-0.744

Ser-GCU3.022390.87371.112010.08361-1.443

Arg-CCU2.614020.635731.109090.12204-1.237

Sec-UCA10.732880.179030.982760.455890.423

Thr-UGU2.791380.004850.958740.14684-1.542

Met-i5.145860.286850.945250.02846-2.445

Trp-CCA3.71460.276330.935160.1088-1.990

Phe-GAA2.116090.343760.912240.31935-1.214

Arg-UCU2.414170.652360.824090.15629-1.551

Ala-CGC0.759960.03750.730380.29535-0.057

Ser-CGA2.157040.714340.721130.08719-1.581

Leu-UAA1.430610.115050.670520.10534-1.093

Ser-IGA/UGA2.638970.526460.658340.01926-2.003

Leu-CAG2.051010.227620.650740.13045-1.656

Leu-CAA1.834630.142290.650650.06785-1.496

Leu-IAG/UAG0.997450.1190.584310.03237-0.772

Val-UAC1.053270.136390.541150.12489-0.961

Thr-CGU1.371450.014210.481580.01917-1.510

Ala-IGC/CGC/UGC0.363350.041140.409020.181430.171

Sec-UCA20.337760.07780.223780.05677-0.594

Leu-UAA20.828320.177070.180240.07853-2.200

--

Fig3B

--averageerror

--HIV WTHIV WT

Lys317.732910.2225

Lys1,216.891671.51726

Asn-GUU10.624751.43541

Glu-CUC/UUC4.208870.1755


Ile-UAU4.11520.09009

Thr-IGU/CGU3.974360.66775

Gly-GCC/CCC2.699340.10931

Asp-GUC2.615540.97891

Arg-CCG/UCG2.544680.0461

Met-CAU2.118140.67272

Gly-UCC1.86260.87535

His-GUG1.812620.85064

Cys-GCA1.753370.67296

Arg-ICG1.615640.14948

Glu-UUC1.491130.22708

Tyr-GUA1.433040.22857

Gln-CUG/UUG1.393620.06732

Ile-IAU/GAU1.371280.43786

Val-IAC/CAC1.29550.35448

Ser-GCU1.112010.08361

Arg-CCU1.109090.12204

Sec-UCA10.982760.45589

Thr-UGU0.958740.14684

Met-i0.945250.02846

Trp-CCA0.935160.1088

Phe-GAA0.912240.31935

Arg-UCU0.824090.15629

Ala-CGC0.730380.29535

Ser-CGA0.721130.08719

Leu-UAA0.670520.10534

Ser-IGA/UGA0.658340.01926

Leu-CAG0.650740.13045

Leu-CAA0.650650.06785

Leu-IAG/UAG0.584310.03237

Val-UAC0.541150.12489

Thr-CGU0.481580.01917

Ala-IGC/CGC/UGC0.409020.18143

Sec-UCA20.223780.05677

Leu-UAA20.180240.07853

--

Table

Codon familyRSCU HumanRSCU HIV-1log2(RSCUHIV1/Human)RankRSCUtRNAHIV1tRNAGagVLPlog2(tRNAHIV1/GagVLP)RanktRNA--MeanWTMeanMut

Arg(AGA)0.971.440.5780.04940.02770.83684Ala-CGC0.099250.0694

Arg(AGG)1.030.56-0.8840.06600.05440.27942Ala-IGC/CGC/UGC0.113210.07377

Ile(AUA)0.241.592.73141.33970.06144.447714Arg-CCG/UCG0.171890.04214

Ile(AUY)2.641.41-0.9030.26720.13710.96285Arg-CCU0.0660.05438

Leu(UUA)0.681.381.02110.09000.03741.26778Arg-ICG0.13350.04802

Leu(UUG)1.320.62-1.0910.04500.0496-0.13801Arg-UCU0.049420.02767

Lys(AAA)0.761.270.7490.64050.03404.237813Asn-GUU0.458820.04177

Lys(AAG)1.240.73-0.7651.00810.06014.068712Asp-GUC0.130290.05737

Gly(GGA)0.932.081.16120.07080.02901.28929Cys-GCA0.082810.02661

Gly(GGB)3.071.92-0.6860.20160.04862.053110Gln-CUG/UUG0.058650.02139

Val(GUA)0.392.082.42130.06620.02821.22897Glu-CUC/UUC0.157570.04896

Val(GUB)3.611.92-0.9120.07390.04850.60613Glu-UUC0.054240.01918

Thr(ACA)0.971.941.00100.04810.02151.16426Gly-GCC/CCC0.201640.04859

Thr(ACB)3.032.06-0.5670.25220.03472.861511Gly-UCC0.070750.02895

0.32246362160.578021978His-GUG0.209870.10221

Ile-IAU/GAU0.267240.13711

Ile-UAU1.339670.06139

SUMMARY OUTPUTLeu-CAA0.045040.04956

Leu-CAG0.031960.02157

Regression StatisticsLeu-IAG/UAG0.079650.04178

Multiple R0.5780219780.5780219780.0303830139Leu-UAA0.090.03738

R Square0.3341094071Leu-UAA20.00780.01543

Adjusted R Square0.2786185243Lys1,21.008130.06008

Standard Error3.5530516214Lys30.640520.03395

Observations14mAla0.008450.0089

mArg0.015480.01881

ANOVAmAsn0.017520.01356

dfSSMSFSignificance FmAsp0.026590.02775

Regression176.009890109976.00989010996.02097841230.0303830139mCys0.004510.00371

Residual12151.490109890112.6241758242Met-CAU0.184240.04164

Total13227.5Met-i0.026230.0161

mGln0.030420.02478

CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%mGlu0.027030.02208

Intercept3.16483516482.0057639441.57787020470.1405793728-1.20534904457.5350193742-1.20534904457.5350193742mGly0.005640.00456

RankRSCU0.5780219780.23556502872.45376820670.03038301390.06476987191.09127408420.06476987191.0912740842mHis0.015730.00907

mIle0.011240.00955

mLeu-UAA0.014480.01134

mLeu-UAG0.007640.0061

mLys0.012970.00964

mMet0.0180.01466

mPhe0.01940.01964

mPro0.021320.01737

mSer-GCU0.013010.03218

mSer-UGA0.008550.00753

mThr0.008290.00768

mTrp0.006070.00485

mTyr0.00990.01046

mVal0.018480.01324

Phe-GAA0.046840.01751


Sec-UCA10.269970.0297

Sec-UCA20.078830.06011

Ser-CGA0.05150.02244

Ser-GCU0.060460.01963

Ser-IGA/UGA0.016610.01061

Thr-CGU0.062150.01921

Thr-IGU/CGU0.190040.01549

Thr-UGU0.048140.02148

Trp-CCA0.035750.01846

Tyr-GUA0.068330.0362

Val-IAC/CAC0.073870.04853

Val-UAC0.066170.02823

Table

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RanktRNA

RankRSCU

RanktRNA

FIg1

HIV-1HTLV-1

AACodonRSCUHumA-endingC-endingG-endingU-endingA-endingC-endingG-endingU-endingEnding

AGCA0.74202898552.02666666670.51A

EGAA0.78346028291.30708661421.224A

GGGA0.92817679562.07751937981.18A

IAUA0.35839160841.59414225940.797A

KAAA0.76137339061.26970954361.5A

LCUA0.29585087191.15384615381.073A

LUUA0.67714285711.38235294121.505A

PCCA0.93228655541.95789473680.986A

QCAA0.51993262211.09090909090.945A

RAGA0.97315436241.44329896910.788A

RCGA0.75247524752.26666666670.932A

SUCA0.79188900752.11494252870.815A

TACA0.97052541651.88018433180.821A

VGUA0.38819875782.08144796380.583A

AGCC1.74057971010.82.438C

CUGC1.20276953510.41176470591.435C

DGAC1.17019230770.91176470591.234C

FUUC1.19561454130.74418604651.073C

GGGC1.5453827940.52713178291.28C

HCAC1.18640576730.71264367821.228C

IAUC1.69055944060.5397489541.219C

LCUC1.06674684310.69230769231.404C

NAAC1.16544117650.61728395061.108C

PCCC1.46418056920.69473684211.729C

RCGC1.60936093610.53333333331.233C

SAGC1.404761904811.281C

SUCC1.60939167560.82758620692.222C

TACC1.7291755660.92165898621.932C

VGUC1.01397515530.41628959281.75C

YUAC1.19484702090.50549450551.307C

AGCG0.34347826090.21333333330.303G

EGAG1.21653971710.69291338580.776G

GGGG0.87134964481.0232558141.06G

KAAG1.23862660940.73029045640.5G

LCUG2.11906193631.28205128210.581G

LUUG1.32285714290.61764705880.495G

PCCG0.47301275760.16842105260.425G

QCAG1.48006737790.90909090911.055G

RAGG1.02684563760.55670103091.212G

RCGG1.11611161121.06666666671.053G

SUCG0.36926360730.22988505750.148G

TACG0.37761640320.18433179720.256G

VGUG1.93478260870.88687782810.861G

AGCU1.17391304350.960.749U

CUGU0.79723046491.58823529410.565U

DGAU0.82980769231.08823529410.766U

FUUU0.80438545871.25581395350.927U

GGGU0.65509076560.37209302330.48U

HCAU0.81359423271.28735632180.772U

IAUU0.9510489510.86610878660.984U

LCUU0.51834034880.87179487180.942U

NAAU0.83455882351.38271604940.892U

PCCU1.13052011781.17894736840.86U

RCGU0.52205220520.13333333330.782U

SAGU0.595238095210.719U

SUCU1.22945570970.82758620690.815U

TACU0.92268261431.01382488480.991U

VGUU0.66304347830.61538461540.806U

YUAU0.80515297911.49450549450.693U

FIg1

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A-ending

C-ending

G-ending

U-ending

RSCU (Human)

RSCU (HIV-1)

V

T

S

R

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A

Fig.2

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A-ending

C-ending

G-ending

U-ending

RSCU (Human)

RSCU (HTLV-1)

EarlyLate

AACodonEndingRSCUHumRSCUHIV1LateRSCUHIV1EarlyRSCUHTL1LateRSCUHTL1EarlySUMMARY OUTPUT: LateRSCUHumRSCUHIV1LateSUMMARY OUTPUTAACodonRSCUHumRSCUHIV1Late

AGCAA-A0.74202898552.1221.6670.5430.6150.74202898552.122AGCA0.74202898552.122

EGAAE-A0.78346028291.4140.7271.2241.231Regression Statistics1.74057971010.805Regression StatisticsAGCC1.74057971010.805

GGGAG-A0.92817679562.1261.7331.3621.28Multiple R0.47718215290.34347826090.171Multiple R0.054264191AGCG0.34347826090.171

IAUAI-A0.35839160841.6430.6430.7650.75R Square0.22770280711.17391304350.902R Square0.0029446024AGCU1.17391304350.902

KAAAK-A0.76137339061.3590.7621.4471.417Adjusted R Square0.20790031491.17019230770.887Adjusted R Square-0.0326645189DGAC1.17019230770.887

LCUAL-A0.29585087191.1581.121.1190.909Standard Error0.38156973990.82980769231.113Standard Error0.5464828602DGAU0.82980769231.113

PCCAP-A0.93228655542.0811.4120.9550.988Observations410.78346028291.414Observations30EGAA0.78346028291.414

QCAAQ-A0.51993262211.1170.9521.0150.6291.21653971710.586EGAG1.21653971710.586

RAGAR-A0.97315436241.4611.53811.143ANOVA1.18640576730.73ANOVAGGGA0.92817679562.126

TACAT-A0.97052541651.9511.50.7870.733dfSSMSFSignificance F0.81359423271.27dfSSMSFSignificance FGGGC1.5453827940.421

VGUAV-A0.38819875782.1591.20.6340.667Regression11.67415778681.674157786811.49869448830.00160720860.29585087191.158Regression10.02469553830.02469553830.08269236390.7757990677GGGG0.87134964481.011

AGCC1.74057971010.8050.8332.3432.769Residual395.67822318880.14559546641.06674684310.737Residual288.36201846170.2986435165GGGU0.65509076560.442

DGAC1.17019230770.8870.751.2571.273Total407.35238097562.11906193631.333Total298.386714HCAC1.18640576730.73

GGGC1.5453827940.4210.81.2771.60.51834034880.772HCAU0.81359423271.27

HCAC1.18640576730.730.7141.1651CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%0.93228655542.081CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%IAUA0.35839160841.643

IAUCI-C1.69055944060.4521.7141.2241.2Intercept0.55138258120.1451056823.7998689890.0004956790.25787863850.8448865240.25787863850.8448865241.46418056920.748Intercept0.93557266010.24525795383.81464758020.00068916520.43318452251.43796079760.43318452251.4379607976IAUC1.69055944060.452

LCUC1.06674684310.7370.481.2661.545RSCUHum0.4486418090.13230476193.39097249890.00160720860.1810301710.71625344710.1810301710.71625344710.47301275760.065RSCUHum0.06442733990.2240461560.28756279990.7757990677-0.39451040010.5233650799-0.39451040010.5233650799IAUU0.9510489510.905

PCCC1.46418056920.7480.5881.6522.3531.13052011781.106KAAA0.76137339061.359

SAGC1.40476190480.8721.21.3850SUMMARY OUTPUT: early0.51993262211.117KAAG1.23862660940.641

TACC1.7291755660.86411.772.7331.48006737790.883LCUA0.29585087191.158

VGUC1.01397515530.4090.61.8051.667Regression Statistics1.40476190480.872LCUC1.06674684310.737

AGCG0.34347826090.1710.1670.2860Multiple R0.36769703540.59523809521.128LCUG2.11906193631.333

EGAG1.21653971710.5861.2730.7760.769R Square0.13520110990.92817679562.126LCUU0.51834034880.772

GGGG0.87134964481.0111.20.8511.12Adjusted R Square0.11302677931.5453827940.421PCCA0.93228655542.081

KAAG1.23862660940.6411.2380.5530.583Standard Error0.61577178190.87134964481.011PCCC1.46418056920.748

LCUG2.11906193631.3331.120.6610.455Observations410.65509076560.442PCCG0.47301275760.065

PCCG0.47301275760.0650.5880.3780.1880.97052541651.951PCCU1.13052011781.106

QCAG1.48006737790.8831.0480.9851.371ANOVA1.7291755660.864QCAA0.51993262211.117

RAGG1.02684563760.5390.46210.857dfSSMSFSignificance F0.37761640320.222QCAG1.48006737790.883

TACG0.37761640320.2220.1670.1970.267Regression12.31190139282.31190139286.09719016160.01802421050.92268261430.963RAGA0.97315436241.461

VGUG1.93478260870.7731.80.8290.667Residual3914.78782060720.3791748874-0.14360111660.054264191RAGG1.02684563760.539

AGCU1.17391304350.9021.3330.8290.615Total4017.099722SAGC1.40476190480.872

DGAU0.82980769231.1131.250.7430.727SAGU0.59523809521.128

GGGU0.65509076560.4420.2670.5110CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%TACA0.97052541651.951

HCAU0.81359423271.271.2860.8351Intercept0.47278688790.23416947162.0189945540.0503998903-0.00086557170.9464393476-0.00086557170.9464393476TACC1.7291755660.864

IAUU0.9510489510.9050.6431.011.05RSCUHum0.52721311210.213511532.46924890640.01802421050.09534528290.95908094120.09534528290.9590809412TACG0.37761640320.222

LCUU0.51834034880.7721.280.9541.091TACU0.92268261430.963

PCCU1.13052011781.1061.4121.0150.471VGUA0.38819875782.159

SAGU0.59523809521.1280.80.6152VGUC1.01397515530.409

TACU0.92268261430.9631.3331.2460.267VGUG1.93478260870.773

VGUU0.66304347830.6590.40.7321VGUU0.66304347830.659

0.54440046870.7330651607

PCCAP-A0.93228655542.0811.4120.9550.988

PCCC1.46418056920.7480.5881.6522.353

PCCG0.47301275760.0650.5880.3780.188

PCCU1.13052011781.1061.4121.0150.471

xxia:mininum number of codons/family: 14

EarlyLate

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RSCUHIV1Late

RSCUHIV1Early

RSCU (Human)

RSCU (HIV-1 early and late genes)

A-A

E-A

G-A

I-A

K-A

L-A

P-A

Q-A

R-A

T-A

V-A

I-C

y = 0.3084x + 0.6916R2 = 0.1024

SlopeDiff

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RSCUHTL1Late

RSCUHTL1Early

RSCU (Human)

RSCU (HTLV-1 early and late genes)

y = 0.4486x + 0.5514R2 = 0.2277p = 0.0016

y = 0.5272x + 0.4728R2 = 0.1352p = 0.0180

EarlyLateCAI

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RSCUHIV1Late

RSCU (Human)

RSCU (HIV1-late)

Fig. 2Final

AACodonHumanCFMusCFHIVCFRSCUHumRSCUMusRSCUHIVObsFreqHTL1RSCUHTL1ObsFreqHTL1EarlyRSCUHTL1EarlyObsFreqHTL1LateRSCUHTL1LateObsFreqHIV1EarlyRSCUHIV1EarlyObsFreqHIV1LateRSCUHIV1LateRSCUAACodonRSCUHIV1EarlyRSCUHIV1Late

AGCA51234611140.74200.85672.0267320.5140.615190.543101.667872.122Codon familyRank(Isupply)HIV1EarlyHIV1LateGGGA1.7332.126

AGCC12016299451.74061.55920.80001532.438182.769822.34350.833330.805Arg(AGA)41.5381.461GGGC0.80.421

AGCG2371499120.34350.37100.2133190.30300100.28610.16770.171Arg(AGG)20.4620.539GGGG1.21.011

AGCU8104901541.17391.21310.9600470.74940.615290.82981.333370.902Ile(AUA)140.6431.643GGGU0.2670.442

CUGC6083055141.20281.05640.4118611.43581331.46750.83380.348Ile(AUY)52.3571.357HCAC0.7140.73

CUGU4032729540.79720.94361.5882240.56581120.53371.167381.652Leu(UUA)81.2501.358HCAU1.2861.27

DGAC12176493621.17021.13820.9118871.234141.273441.25760.75470.887Leu(UUG)10.7500.642IAUA0.6431.643

DGAU8634916740.82980.86181.0882540.76680.727260.743101.25591.113Lys(AAA)130.7621.359IAUC1.7140.452

EGAA108064651660.78350.81391.3071711.224161.231301.224120.7271281.414Lys(AAG)121.2380.641IAUU0.6430.905

EGAG16779421881.21651.18610.6929450.776100.769190.776211.273530.586Gly(GGA)91.7332.126KAAA0.7621.359

FUUC10365193321.19561.17560.7442661.073200.909331.15830.667240.727Gly(GGB)102.2671.874KAAG1.2380.641

FUUU6973642540.80440.82441.2558570.927241.091240.84261.333421.273Val(GUA)71.2002.159LCUA1.121.158

GGGA58846521340.92821.08972.0775591.18161.28321.362131.7331012.126Val(GUB)32.8001.841LCUC0.480.737

GGGC9795667341.54541.32740.5271641.28201.6301.27760.8200.421Thr(ACA)61.5001.951LCUG1.121.333

GGGG5523722660.87130.87181.0233531.06141.12200.85191.2481.011Thr(ACB)112.5002.049LCUU1.280.772

GGGU4153036240.65510.71110.3721240.4800120.51120.267210.442LUUA1.251.358

HCAC5763671311.18641.23560.7126891.228161461.16550.714230.73LUUG0.750.642

HCAU3952271560.81360.76441.2874560.772161330.83591.286401.27RAGA1.5381.461

IAUA20514441270.35840.40041.5941510.797100.75250.76530.6431091.643RAGG0.4620.539

IAUC9675728431.69061.58820.5397781.219161.2401.22481.714300.452RCGA31.714

IAUU5443648690.95101.01150.8661630.984141.05331.0130.643600.905RCGC0.3330.857

KAAA88753381530.76140.74501.26971111.5171.417551.44780.7621251.359RCGG0.6671.143

KAAG14438993881.23861.25500.7303370.570.583210.553131.238590.641RCGU00.286

LCUA2461713450.29590.36951.15381071.073200.909611.11971.12331.158SAGC1.20.872

LCUC8874765271.06671.02780.69231401.404341.545691.26630.48210.737SAGU0.81.128

LCUG17629179502.11911.97991.2821580.581100.455360.66171.12381.333SUCA12.169

LCUU4312887340.51830.62270.8718940.942241.091520.95481.28220.772SUCC10.814

LUUA2371153940.67710.57051.3824701.50541381.43451.25741.358SUCG0.3330.203

LUUG4632889421.32291.42950.6176230.49541150.56630.75350.642SUCU1.6670.814

MAUG1012539777391017655TACA1.51.951

NAAC9515391501.16541.16900.6173721.108101.111381.01371.167360.571TACC10.864

NAAU68138321120.83460.83101.3827580.89280.889370.98750.833901.429TACG0.1670.222

PCCA4754201930.93231.13721.95791090.986210.988480.955121.412642.081TACU1.3330.963

PCCC7464621331.46421.25090.69471911.729502.353831.65250.588230.748VGUA1.22.159

PCCG241152780.47300.41330.1684470.42540.188190.37850.58820.065VGUC0.60.409

PCCU5764428561.13051.19861.1789950.86100.471511.015121.412341.106VGUG1.80.773

QCAA46330641140.51990.56131.09091200.945110.629681.015100.952861.117VGUU0.40.659

QCAG13187854951.48011.43870.90911341.055241.371660.985111.048680.883

RAGA43529901400.97321.01721.4433130.78841.14391201.5381031.461

RAGG4592889541.02680.98280.5567201.21230.8579160.462380.539

RCGA2091507170.75250.82322.2667310.93271.273160.979361.714

RCGC447247141.60941.34970.5333411.23371.273231.39410.33330.857

RCGG310215081.11611.17441.0667351.05330.545160.9720.66741.143

RCGU145119510.52210.65270.1333260.78250.909110.6670010.286

SAGC8264679531.40481.28631.0000411.28100271.38591.2340.872

SAGU3502596530.59520.71371.0000230.71942120.61560.8441.128

SUCA3712798460.79190.93512.1149440.81580.681300.98431322.169

SUCC7544382181.60941.46440.82761202.222252.128632.06631120.814

SUCG173106450.36930.35560.229980.14820.1750.16410.33330.203

SUCU5763725181.22951.24490.8276440.815121.021240.78751.667120.814

TACA56837511020.97051.09521.8802480.821110.733240.78791.5791.951

TACC10125099501.72921.48880.92171131.932412.733541.7761350.864

TACG2211446100.37760.42220.1843150.25640.26760.19710.16790.222

TACU5403404550.92270.99391.0138580.99140.267381.24681.333390.963

VGUA25015511150.38820.42182.0814210.58340.667130.63461.2952.159

VGUC6533822231.01401.03930.4163631.75101.667371.80530.6180.409

VGUG12466962491.93481.89310.8869310.86140.667170.82991.8340.773

VGUU4272375340.66300.64580.6154290.80661150.73220.4290.659

WUGG572339298721340881

YUAC7424116231.19481.17850.5055661.307221.833291.05561.091150.429

YUAU5002869680.80520.82151.4945350.69320.167260.94550.909551.571

*UAA44284240201

*UAG20197700034

*UGA68669122010

401672403783568

DiffMutationEarlyLate

AACodonRSCUHIV1LateRSCUHumHumGGroupSUMMARY OUTPUT

AGCA2.1220.742028985500

AGCC0.8051.740579710100Regression Statistics

AGCG0.1710.343478260900Multiple R0.2990972868

AGCU0.9021.173913043500R Square0.089459187

DGAC0.8871.170192307700Adjusted R Square0.0415359863

DGAU1.1130.829807692300Standard Error0.5284094753

EGAA1.4140.783460282900Observations41

EGAG0.5861.216539717100

GGGA2.1260.928176795600ANOVA

GGGC0.4211.54538279400dfSSMSFSignificance F

GGGG1.0110.871349644800Regression21.04243820520.52121910261.86671978660.1685345406

GGGU0.4420.655090765600Residual3810.61022979480.2792165735

HCAC0.731.186405767300Total4011.652668

HCAU1.270.813594232700

IAUA1.6430.35839160841.6431CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

IAUC0.4521.69055944060.4521Intercept1.03873697990.215347174.82354599670.00002300370.60278942941.47468453040.60278942941.4746845304

IAUU0.9050.9510489510.9051RSCUHum-0.11143043250.1864465213-0.5976535880.5536162996-0.4888716790.266010814-0.4888716790.266010814

KAAA1.3590.76137339061.3591HumG0.27094832330.15985659261.69494619420.0982666541-0.05266442710.5945610738-0.05266442710.5945610738

KAAG0.6411.23862660940.6411

LCUA1.1580.295850871900

LCUC0.7371.066746843100SUMMARY OUTPUT

LCUG1.3332.119061936300

LCUU0.7720.518340348800Regression Statistics

PCCA2.0810.932286555400Multiple R0.2844298639

PCCC0.7481.464180569200R Square0.0809003475

PCCG0.0650.473012757600Adjusted R Square0.0573336897

PCCU1.1061.130520117800Standard Error0.5240366769

QCAA1.1170.519932622100Observations41

QCAG0.8831.480067377900

RAGA1.4610.97315436241.4611ANOVA

RAGG0.5391.02684563760.5391dfSSMSFSignificance F

SAGC0.8721.404761904800Regression10.94270488990.94270488993.43283075120.0714906748

SAGU1.1280.595238095200Residual3910.70996311010.2746144387

TACA1.9510.970525416500Total4011.652668

TACC0.8641.72917556600

TACG0.2220.377616403200CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

TACU0.9630.922682614300Intercept0.9225583630.091896290610.03912515400.7366805721.10843615390.7366805721.1084361539

VGUA2.1590.38819875782.1591HumG0.28864610160.15578997241.85278999110.0714906748-0.02646885810.6037610612-0.02646885810.6037610612

VGUC0.4091.01397515530.4091

VGUG0.7731.93478260870.7731

VGUU0.6590.66304347830.6591

xxia:0: Codon families without documented selective packaging1: with selective packaging, i.e., those in Table 1 other than Thr and Gly.

SeqSeqLenCAICAI2t-Test: Two-Sample Assuming Unequal Variances

tat2610.668750.71957

rev3510.662110.72057Variable 1Variable 2

nef6210.675230.72625Mean0.66869666670.592736

gag-pol43080.591630.6524Variance0.00004303570.0035822537

vif5790.619410.68549Observations35

vpr2910.642720.69085Hypothesized Mean Difference0

vpu2490.490680.56748df4

env25710.619240.68272t Stat2.8098988703

P(T

Table 2. Frequency of A residues, length and codon adaptation index (CAI) for the three HIV-1 early (tat, rev and nef) and five late (gag-pol, vif, vpu, vpr, and env) coding sequences (CDS). Any problem with the mutation hypothesis?

GeneCDS (bp)CAItat2610.66875rev3510.66211nef6210.67523

gag15030.62784pol30120.58139vif5790.61941vpr2910.64272vpu2490.49068env25710.61924

You may be wondering about Cys codon family which has 4 tRNAs matching UGC, but none matching UGU. We would have predicted that UGC should be preferred, but the opposite is true. Why? One might think that, because Cys is rarely used, the codon family is not under selection, so that codon usage will be at the mercy of mutation bias. Because the yeast genome is AT-biased, we expect U-ending codon to be more than C-ending codon. Are you happy with this explanation? Unfortunately, the explanation is wrong, but the correct answer is still elusive.

codon usage bias ref: chapter 9 xuhua xia [email protected] http:// dambe.bio.uottawa.ca

Documents

differential codon usage

codon usage biasindices

genomic codon usage

codon usage biasobservation

elongationmet codon

biased codon usage

codon usage biasref

codon families