Table 1 GWAS and computational analyses results of SNPs associated with drug resistance phenotype

From: Genome wide analyses reveal the role of mutator phenotypes in Mycobacterium tuberculosis drug resistance emergence

DNA Repair Systems

Protein

SNP

Nb. (strains)Fr. (%)

Lineage

Association with resistance (P-value)

TreeWAS (Ter./Sub. P-values)

CL

Mutation effect score

ER

DNA replication

DnaE1

Ser898Leu

782 (1.46)

L2

< 2.2e-16

0/0

E.R (4)

−6.423

26.55

PolD2

Asp132Asn

80 (0.15)

L4

< 2.2e-16

0/0

E.R (5)

−5.765

1.203

BER

MutM

Glu256Asp

295 (0.55)

L4

< 2.2e-16

0/0

E.R (5)

−5.961

10.064

Fpg2

Tyr50His

782 (1.46)

L2

< 2.2e-16

0/0

S.R (9)

−7.554

13.098

XthA

Trp85Arg

445 0.83

L2

< 2.2e-16

0/0

F.R (8)

−6.442

16.615

MutY

Arg262Gln

268 (0.50)

L4

< 2.2e-16

0/0

E.R (4)

−3.123

4.073

Nei1

Ala99Thr

241 (0.45)

L4

< 2.2e-16

0/0

E.R (1)

−2.49

32.141

MutT3

Trp196Gly

27 (0.05)

L4

< 2.2e-16

0/0

S.R (9)

−7.423

1.782

NER

UvrA

Gln135Lys

241 (0.45)

L4

< 2.2e-16

0/0

E.R (7)

−3.456

0.879

UvrB

Leu177Arg

204 (0.38)

L2

< 2.2e-16

0/0

E.R (4)

−10.161

5.431

UvrD2

Glu331Gly

1066 (1.99)

L2

< 2.2e-16

0/0

E.R (1)

−1.92

1.987

HR

RecA

Ile395Val

482 (0.90)

L2

< 2.2e-16

0/0

E.R (3)

−2.22

28.668

SSBb

Pro121Ala

113 (0.21)

L4

< 2.2e-16

0/0

F.R (6)

−3.561

56.521

RuvA

Arg39Trp

461 (0.86)

L2

< 2.2e-16

0/0

E.R (5)

−9.399

74.956

RuvB

Glu344Gly

54 (0.10)

L4

< 2.2e-16

0/0

E.R (6)

−3.345

6.067

Other proteins

RecC

Arg484Ser

579 (1.08)

L2

< 2.2e-16

0/0

E.R (4)

−1.804

6.866

RecN

Glu130Gly

155 (0.29)

L2

< 2.2e-16

0/0

E.R (3)

−0.406

1.02

RecGwed

Ile39Val

429 (0.80)

L4

< 2.2e-16

0/0

E.R (3)

−4.658

1.021

  1. P-Values from two TreeWAS scores are provided, Terminal (Ter) and Subsequent (Sub) scores respectively. P-value = 0 for TreeWAS output indicates a P-value < 10-6. We computed the amino acid conservation level (CL) using the ConSurf tool (E.R. Exposed Residue, F.R. functional residue, S.R. structural residue). We computed the Evolutionary Coupling between sites (EcS) and using the EVcouplings server. We predicted the effect mutation strength using the EVmutation server ( < 0: damaging effect). We used Busted to estimate the proportion of sites under positive selection and the strength of selection at each site (ER Evidence rate ≥ 10 for positive selection). The proteins and SNPs highlighted in bold represent those selected for the experimental phase.
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