Table 2.

Regulatory Proteins with Predicted Functional SNPs and Indels in Lineages 1 and 2

Gene	Regulator Type	SNPa	Mutation	Lineage	SIFT Score	Domain	Protein Stabilityb
High predictive score
Rv0275	TetR	T 331588 C	L24S	Modern	0.00	HTH	−3.18
NarL	2-component regulator	G 940602 C	G169R	2	0.00	HTH	−4.66
KdpD	2-component sensor	Indel	H67 frameshift	1	n/a	2-component sensor	n/a
BlaI	penicillinase repressor	T 2096430 G	L57R	1	0.05	HTH	−8.72
SirR	Fe-dependent repressor	C 3097349	Q131X	1	n/a	Fe-dependent repressor	n/a
VirS	AraC	T 3447480 G	L316R	1	0.01	HTH	−2.03
Rv3167c	TetR	C 3536008 A	P17Q	1	0.02	HTH	-1.21
Rv3830c	TetR	Indel	S208 frameshift fusion	2	n/a	Low complexity	n/a
Low predictive score
RamB	HTH-XRE	A 555945 G	Q121R	1	0.02	Low complexity	n/a
Rv0377	LysR	G 455325 C	R302P	2	0.00	Low complexity	n/a
MprA	2-component regulator	A 1097023 G	S70G	Modern	0.04	cheY	+2.83
TcrS	2-component sensor	C 1157771 G	S62C	1	0.01	Low complexity	n/a
Zur	Fur	G 2641840 A	R64H	Modern	0.02	HTH	+0.47
Rv3736	AraC	G 4187063 A	G144R	1	0.01	Arabinose-binding	n/a

Note.—High predictive score: SNPs map to HTH DNA-binding domains of regulator and predicted to cause a loss of protein stability. Low predictive score: SNPs outside of HTH domain or in low-complexity regions and no loss of protein stability.

^aAlleles are the ancestral and mutant with genomic position based on H37Rv.

^bn/a: change in stability not possible due to stop codon or indel mutation or no protein structure over position.