Genetic features of Mycobacterium tuberculosis modern Beijing sublineage

Figures & data

Figure 1 Maximum-likelihood phylogeny of 1082 MTB Beijing isolates. Strains shown in gray shadow represent modern Beijing sublineage while others belong to ancient Beijing sublineage. The two dark circles represent the MRCA sequences of modern Beijing strains and the closest ancient branch, respectively. Ancient Beijing strain 1-6 that harbored mutT2 G58R mutation but not IS6110 insertion in NTF region is marked in the phylogeny.

Table 1 Genes with significant alterations in modern Beijing strains

Gene name	Genetic changes	Alteration	Cellular localization	Description
Rv1730c	19 bp deletion from codon 438 to 444	517–>418 amino acids	Cell wall and cell processes	Essential, possible penicillin-binding protein, involved in cell wall biosynthesis and may also act as a sensor of external penicillin
Rv2147c	1 bp deletion in start codon	241–>218 amino acids	Cell membrane	Essential, a core mycobacterial gene, conserved in mycobacterial strains
Rv2148c	1 bp deletion in codon 258	Frameshift of 5 amino acids	Cell membrane	Nonessential, conserved protein, function unknown
Rv2180c	A premature stop codon mutation	295–>249 amino acids	Cell wall and cell processes	Nonessential, probable conserved integral membrane protein, function unknown

Table 2 Modern Beijing-specific mutations that are enriched in the gene category of regulatory network and other mutations with potential functional effects

Categories	Gene	Codon change	Gene description
Regulatory network	pknA	Q370P	Transmembrane serine/threonine protein kinase A
		Q369R	Transmembrane serine/threonine protein kinase A
	Rv0452	H125D	Possible transcriptional regulatory protein
	Rv0890c	E234G	Probable LuxR family transcriptional regulatory protein
	Rv2488c	T265I	Transcriptional regulator, LuxR family
	Rv3173c	Promoter mutation	TetR/AcrR family transcriptional regulator
Other categories	secA2	V410M	Possible preprotein translocase ATPase SecA2
	sseA	E276K	Probable short-chain dehydrogenase/reductase
	glcB	G104S	Probable malate synthase G GlcB

Figure 2 Modern Beijing-specific SNPs alter the expression level of downstream genes. The promoters with modern Beijing-specific mutations have been tested for transcriptional activity against promoters without respective mutations through luciferase report system in M. smegmatis. Data presented are mean values from three independent experiments. Error bars, 95% confidence intervals.