. 2019 Feb 11;11(3):814–831. doi: 10.1093/gbe/evz031

Table 1.

List of Genes Mutated in Five or More Populations at Generation 1000

Mutated gene		Antibiotic	Gene Version			Amino Acid Change or Mutation; Protein Length (p.l.)	Protein Function
Mutated gene		Antibiotic	AT	GC	OPT	Amino Acid Change or Mutation; Protein Length (p.l.)	Protein Function
Significant effect of antibiotic	adhE	AMP				A392V(3), L571V, F583L(3), A626V, A626T, D672N; p.l.: 891 aa	Fused acetaldehyde-CoA dehydrogenase and iron-dependent alcohol dehydrogenase—inhibited by chloramphenicol
	adhE	CAM
	arcA	AMP				I55V, R67C, N85D, N85H, V87A, E94G, E86G, D99G(3), N106T, T126A; p.l.: 239 aa	Global regulator. Regulates genes involved in redox metabolism
	arcA	CAM
	acrB	AMP				IS10 2, ins 1 bp 73(2), A286D, IS1 3049; p.l.: 1,050 aa	Component of a multidrug efflux pump
	acrB	CAM				IS10 2, ins 1 bp 73(2), A286D, IS1 3049; p.l.: 1,050 aa	Component of a multidrug efflux pump
	sucC	AMP				W248R, V263V, G292A, E350G(3), Q247R, A354V, L255R, I259S; p.l.: 388 aa	Succinyl CoA synthase beta-subunit
	sucC	CAM					Succinyl CoA synthase beta-subunit
	fabR	AMP				T46A, insT 534, IS2 42, IS10 124(2), IS2 366, IS150 557; p.l.: 216 aa	Fatty acid biosynthesis regulator
	fabR	CAM					Fatty acid biosynthesis regulator
Significant effect of gene version	spoT	AMP				S103P, H179R, Y286H, G314S, Y391C, N456H; p.l. 702 aa	Guanosine-3′,5′-bis(diphosphate) 3′-pyrophosphohydrolase (both synthesizes and hydrolyzes the alarmone [p]ppGpp)
	spoT	CAM				S103P, H179R, Y286H, G314S, Y391C, N456H; p.l. 702 aa
	fadE	AMP				Y158H, E323K(2), Y713H; p.l.: 814 aa	Fatty acid degradation, starvation inducible
	fadE	CAM				Y158H, E323K(2), Y713H; p.l.: 814 aa	Fatty acid degradation, starvation inducible
	fruA	AMP				S86P, A431V, C472R, Y548D, IS10 1387, del 1bp 829, ins 1 bp 1382, IS10 1387, del 1bp 1492; p.l.: 564 aa	Fructose permease (membrane spanning protein)
	fruA	CAM					Fructose permease (membrane spanning protein)
	mdoB	AMP				IS10 1870(4), T > C 317; pseudogene length: 2,009 nt	Pseudogene
	mdoB	CAM				IS10 1870(4), T > C 317; pseudogene length: 2,009 nt	Pseudogene
	putP slt	AMP				putP (D55G[2], I254V, I435F; p.l.: 502 aa), slt (G198D, ins 1 bp 275, ins 1 bp 1223; p.l.: 646 aa)	PutP: Na+/l-proline transporter; Slt: soluble lytic transglycosylase, cleaves murein residues
	putP slt	CAM
^a	rpsG	AMP				Y154C, L157*(2); p.l.: 179 aa	30S ribosomal subunit protein S7
^a	rpsG	CAM				Y154C, L157*(2); p.l.: 179 aa	30S ribosomal subunit protein S7
	mutL	AMP				IS10 977(3), IS10 1423(2); p.l.: 616 aa	Methyl-directed mismatch repair protein
	mutL	CAM				IS10 977(3), IS10 1423(2); p.l.: 616 aa	Methyl-directed mismatch repair protein
	cytR	AMP				Y53D, del 1 bp 138, IS4 142(2), L204P, A257P, IS10 292, IS10 624 (2); p.l.: 342 aa	Antiactivator (TF) for nucleoside utilization regulon. Controls genes involved in (deoxy)nucleoside uptake and metabolism
	cytR	CAM
	mutS	AMP				IS10 1552(2), IS10 1999(2), IS10 2463(2); p.l.: 854 aa	Methyl-directed mismatch repair protein
	mutS	CAM				IS10 1552(2), IS10 1999(2), IS10 2463(2); p.l.: 854 aa	Methyl-directed mismatch repair protein
	clpX ydeK	AMP				clpX (T199A[2], A210V, I301V, Y385C; p.l.: 424 aa), ydeK (insC 781, del 1 bp 3298, del 1 bp 3962, insC 3839; p.l.: 1326 aa)	ClpX: ATPase subunit of ClpXP protease, molecular chaperone; ydeK: reconstructed pseudogene
	clpX ydeK	CAM
	yejG	AMP				S25P, D89G(2), L61P, ins 8 bp 64(2); p.l.: 115 aa	Unknown function
	yejG	CAM				S25P, D89G(2), L61P, ins 8 bp 64(2); p.l.: 115 aa	Unknown function

Note.—The first column indicates the result of the nominal logistic regression (see Material and Methods). Shades of blue in the third column reflect whether 0, 1, 2, or 3 of the replicate populations in each gene version × antibiotic combination were mutated. The fourth column gives the position of the mutations within the protein, with either the corresponding amino acid change, the small indel, or the IS insertion event. Numbers in parentheses/brackets indicate the number of bacterial populations in which the indicated mutation was found. The fifth column describes the function of the protein. “p.l.,” protein length.

^{^a}

Significant effect of the interaction “gene version × antibiotic.”