Mikhail Gelfand Research and Training Center “Bioinformatics”
Post on 13-Jan-2016
26 Views
Preview:
DESCRIPTION
Transcript
Comparative genomic analysis of T-box regulation:
identification of new structural classes and reconstruction of
evolution
Mikhail GelfandResearch and Training Center “Bioinformatics”
Institute for Information Transmission ProblemsMoscow, Russia
Burnham Institute, October 2008To Andrei Osterman
on the occasioin of his Nth birthday
T-boxes: the mechanism (Grundy & Henkin; Putzer & Grunberg-
Manago)
Terminator(underlined) ===========> <===========
Antiterminator ==> ===> <===<== SA serS -> 26 CGTTA 51 AAATAGGGTGGCAACGCGTAGAC------------CACGTCCCTTGTAGGGATGTGGTCTTTTTTTA DHA tyrZ -> 47 CGTTA 65 AGGTAAGGTGGTAACACGGGAGCA-------TACTCTCGTCCTTCTGGCAATGAAGGACGGGAGTTTTTTGTTTT ST trpS -> 37 CCTTA 61 AATTGAGGTGGTACCGCGTATTACTT----GTAATAACGCCCTCACGTTTTAATAGCGTGGGGACTTTTTGCTAT CA aspS -> 39 CGTTA 34 ATAAAGGATGGCACCGTGAAAA----------GCCTTCACTCCTTACTGGAGTGGAGGCTTTTTTTATTTTAAATAAA DF valS -> 41 CGTTA 77 AATTAAGGTGGTAACGCGAGC------------TTTTCGTCCTTTTTAAAGAGGATGAAGAGCTCTTTTTTATTTCT PN thrS -> 30 CGTTA 38 AATGAAGGTGGAACCACGTTG-------------CGACGTCCTTTCGAGGATGTCGCATTTTTTTATTAG MN ileS -> 89 CGTTA 68 AATTAAGGTGGTACCACGAGC-------------TTTCGTCCTTTGATGAAAGTTCTTTTTTATTGAT DF leuS -> 28 AGCTA 29 AATTAGGGTGGTACCGCGAAGATT-------TATCCTCGTCCCTAAACGTAAGTTTAGTGACGAGGATTTTTTATTTTCA HD argS -> 41 CGTTA 27 AACGAGAGTGGTACCGCGGGTAA---------AAGCTCGCCTCTTTTTAGAAGAGGCGGGTTTTTTATTTT DF proS -> 33 CGTTA 30 AACTAGAGTGGTACCGCGGAAAT-----TAAACCTTTCGTCTCTATACTTGTATAGAGATGAGAGGTTTTTTATATTTTCAGGA ZC lysS -> 46 CGTTA 63 AACTGAGGTGGTACCGCGAAGCTAA-----CAACTCTCGTCCTCAAGATGAATAATCTTGGGGGTGGGAGTTTTTTTGTTGCAT BQ metS -> 55 CGTTA 66 AAATAAGGTGGTACCGCGACTGTTTA---TACAGCCCCGCCCTTATCTTTTTTAGATAAGGGCGGGGCTTTTTATATTTAA MN pheS -> 14 AATTA 20 AAAACGGATGGTACCGCGTGTC-------------AACGCTCCGCTTAAGGAGTTTTGGCACTTTTTTTGTTTT MN glyQ -> 14 AGCTA 23 AATTAGGGTGGAACCGCGTTT------------CAAACGCCCCTATGTCAGTTGGCATGGGAGTGATTGAGCGTGGCTCTTTT ST alaS -> 20 AATTA 18 AATAGAGGTGGTACCGCGGTT--------------TTCGCCCTCTGTGAGATGGACTTGTTTTGTATGGAGGACTATTTGAAA SA trpE -> 32 AATTA 4 AACTAAGGTGGCACCACGGTA-------------ACGCGTCCTTACAGGTATATGCGTTATGTGGTGTCTTTTT BS ilvB -> 50 CGTTA 47 AACAAGGGTGGTACCGCGGAAAGAAA---AGCCTTTTCGCCCCTTTTAGCTATCGCAGTTACTGCGCGGCTGATTGT CA ilvC -> 40 CGTTA 14 AATTTGGGTGGTACCGCGCGACCAAA-----AATTCTCGCCCCAAGCAGGGAATTTTGGCCGTTTTTTTATATAAATAAAT BQ asnA -> 51 CGTTA 62 AATTTGGGTGGTACCGCGGAACC-----AAAGCCTTTCGTCCCAGTTTTTTGGGAAAGAAGGGCTTTTTTTGTTGGCTT BS proB -> 33 CGTTA 30 AATCAAGGTGGTACCACGGAAAC--------CCATTTCGTCCTTATGAATCAGGATGAAATGGGTTTTTTTATTGTAGA SA cysE -> 33 CATTA 62 ATTCAGAGTGGAACCGTGCGG-------------AAGCGCCTCTAACAATACAATTTGTATGTTAGTGGTGCTTTTTTG MN hisC -> 46 CGTTA 50 AATGAAGGTGGAACCACGTGTGT---------GTCAGCGTCCTTGCAAGTTTTTTGCAAGGGCGCTTTTTTGAATAGT DHA pheA -> 41 CGTTA 50 AAAAAGGGTGGTACCGCGTGAC---------TTAACTCGTCCCTTATTTGGGGGTGAGGTAAGTCTTTTTTTATTTA HD serA -> 42 cgtta 57 AATGAGGGTGGCACCGCGGTATG-------AACCTTCCGCCCCTCACGACAGTCGTCGTGTGGGCAGAAGGTTTTTTTACTATCA BQ phhA -> 51 CGTTA 34 AAATAGGGTGGTACCGCGATTC------------TTTCGCCCCTATCGGATTTTCCGATAGGGGCTTTTTCTATTTC EF yxjH -> 40 CGTTA 51 AAAAAAGGTGGTACCGCGATAA-----------TAATCGCCCTTTTACTAGTTACGGCTAGTAAAAGGGCGTTTTTTTATAAA CA yckK -> 38 CGTTA 57 AATTAGAGTGGTACCGTGGAATT-------CAACTTCTGCCTCTAACTATGAGGATAGAAGTTTTTTGTTTTTAT DF yqiX -> 41 CCTTA 30 AAAAAGAGTGGTAACGCGGATAT----------AATTCGTCTCTTAGCTGTAAAGCTAAGGGACTTTTTTGATTTA HD BH0807->74 TGTTA 56 AACTGGGGTGGCACCACGACAAG----------TGATCGTCCCCAAGACTTTTATCAGTCTTGGGGACGTTTTTTTGTTCAT EF yheL -> 8 AATTA 33 AATTAAGGTGGTACCGCGGAGA-----------GATTCGTCCTTATTCTTTAAGGATGAATCTCTCTTTTTATGTAGC BQ ykbA -> 46 CGTTA 45 AACAAGGGTGGAACCACGAATAT--------AACACTCGTCCCTTTTTTAGGGAGGAGTGTTTTTTTATT BQ sdt2 -> 40 CGTTA 56 AATTGAGGTGGTACCACGGTATTAACATTACATATATCGTCCTCTACATGCATATTTGCGTGTAGGGGACTTTTTTATTTTC EF yusC -> 42 CGTTA 60 AATTAAGGTGGTATCACGAAATGA-----CAAACTTTCGTCCTTTTTGCTGTAATAGCAAAAGGATGGAAGTTTTTTTGTTT CA yhaG -> 48 CGTTA 51 AATTTAGGTGGTACCGCGGAAGT---------ATCTCCGTCCTAATTAATAAGATTAGGGCGGAGTTTTTTATTTGC BQ brnQ -> 44 CGTTA 66 AATTAGGGTGGTATCGCGGGTAAA------TATAACTCGTCCCTTTCTTTAGGGACGAGTTTTTTGTGTTCTT REF01723 -> 44 CGTTA 55 AATTGAGGTGGCACCACGAATGC----------GATTCGTCCTCTTGGCTCACAGCCAAGAGGCTTTTTTGTTTTTTTAATA BS yvbW -> 56 CGTTA 32 AACAAGAGTGGTACCGCGGTCAGC--CGAAGGCTCGTCGTCTCTTTATCTATTAGATTAGGTAGGAGACGGCGGGCTTTTTT
Aminoacyl-tRNA synthetases
Amino acid biosynthetic genes
Amino acid transporters
TGG: T-box
Partial alignment of predicted T-boxes
specifier hairpin ===> ==> ===> <=== <== SC<=== SA SERS SER ---GTAGGACAAGTA 19 AGAGAGCTTGTGGTT---AGTGTGAACAAG--- 15 GAA--TCTACCTACTT -> DHA tyrZ Tyr ----AAGAACAAGTA 18 AGAAAGTTGCCGGCT---GATGAGAGGCGCTT 18 GAA--TACCTCTTTGA -> ST trpS Trp ---ATTAGAAGAGTA 16 AGAGAGTTAGTGGTT---GGTGCAAGCTAAC- 12 GAAA-TGGACTAATGA -> CA ASPS ASP -----GAGAAAAGTA 18 AGCGAATTGGGAAAT---GGTGTGAGCCCAA- 15 GAAA-GACATCTCGGA -> DF VALS VAL -GAAGAAGAGGAGTA 16 AGAGAGGAAAATTCACTGGCTGTAAGATTTTC 17 GAAT-GTAGCTTTGGA -> PN THRS THR ----AGAGACAAGTC 18 AGAGAGTGCGTGGTT---GCTGGAAACGCAT- 14 GAT--ACTACTCTTGA -> MN ileS Ile ----CAAAAACACAA 17 AGCGAATAGGTGAT----GGTGTAAGACCTATT 18 -----ATCATTTTGTT -> DF leuS Leu ----CTAGAGCAGTA 19 AGAGGAAGTGGAA-----GGTGAGAACTAATATT 10 GAA--CTTACTAGATT -> HD ARGS ARG -----TGGGAGAGTA 20 AGCGAGTCGGGAT-----GGTGGGAGCCGAT- 14 GAAA-CGCACCCATGA -> DF proS Pro ---AAAGAAATAGTA 18 AGAGAGAAAACGGT----GGTGAGAGTTTTC-- 14 GAA--CCTGTCTTTTA -> ZC lysS Lys ---AAGAGAAGAGTA 19 AGAGAGCTCTGGTA----GCTGAGAAAGAGC-- 15 GAAAAAAGACTTGGAG -> BQ metS Met ---AAAGGAAAAGTA 19 AGAGAGCTTCGGTA----GCTGAGAAGAAGC-- 14 GAACAATGGCCTTTGA -> MN pheS Phe ----TGAGATTAGTA 18 AGGGAATGCGGGGCGTG-ACTGGAAACCCGC- 16 GAA--TTCACTCAGAA -> MN glyQ Gly ---AGAAAGAGAGTT 15 AGCGAACCTGAGAG----AGTGTAAGTCAGGT 14 GACT-GGCACTTTCTC -> ST alaS Ala -AGTTAAGAATTGTT 17 AGAAAAGTGACGGTT---GCTGCGAGTCATT- 17 -----GCTACTTAACT ->
SA trpE Trp TCTAAAGAAATAGTA 22 AGAAAGCTAATGGGT---GATGGGAATTAGC-- 14 GAAT-TGGACTTTGGA -> BS ilvB Leu ---TGAGGATAAGTA 20 AGAGAACCGGGTTA----GCTGAGAACCGG--- 16 GAA--CTCGCCTCAGA -> CA ilvC Val -----AGGAAGAGTA 17 AGAGAGTGAGATACT---GGTGGGAACTCAT-- 13 GAAG-GTAGCCTTTGA -> BQ asnA Asn --AGGACGAGTAGTA 15 AGCGAGTCAGGGGT----GGTGTGAGCCTGA-- 15 GAAG-AACCTCCTGGA -> BS proB Pro -----AGGATTAGTA 18 AGAGAGCAAAATGAACC-GCTGAAACATTTTGC 15 GAA--CCTGCCTTGGA -> SA cysE Cys --CGAAGGATTAGTA 18 AGAGAGTGTACGGTT---GCTGTGAGTACA--- 14 GAA--TGCACCTTCGT -> MN hisC His -----AGAGAAAAAA 16 AGAGAGTATGGGAA----GCTGAAAACATAC-- 15 -----CACATTCTTGA -> DHA pheA Phe -----AAAGAGAGCA 19 AGGGAACTAAAGTCGGAGACTGAAAGCTTTAGT 14 GAGA-TTCACTCTGGA -> HD serA Ser ----GAAGATGAGGA 17 AGAGAGCTGGTGGTT---GCTGTGAACCAGCT- 18 -----AGCCCTTCTGA -> BQ phhA Tyr AGAATCGCAGTAGTA 17 AGAGAGCTAATGGTC---GGTGGAAATTGGC-- 14 GAAT-TACAATTCTGG -> EF yxjH Met -----TAGGAAAGTA 17 AGAGAGACTTTGGTT---GGTGAAAAAAGTT-- 13 GAAAAATGGCCTAGGA ->
CA yckK Cys ----AAGAACCAGTA 17 AGAGAAAAATCTCCAAG-GCTGAAAGGGATTTT 15 GAA--TGCATCTTTGA -> DF yqiX Arg -----AGAGAAAGTA 16 AGCGAGTTAGGGGTT---GGTGTAAGCCTAGC- 14 GAAG-AGAGCTCTGGA -> HD BH0807 Lys ----AGAGAAGAGTA 19 AGAAAGCCTGTAGTT---GCTGAGAACGGGT-- 14 GAAGCAAGACTCTGAG -> EF yheL Tyr -TTATTAGCCCAGTA 19 AGAAAGTCGATGGTT---GCTGCGAATCGAT-- 13 GAAT-TACACTAATAA -> BQ ykbA Thr --GAGGACACGATCA 16 AGAGAGGGAAGCCTTTG-GCTGTGAGCTTCCT- 14 GATT-ACCACCTCTGA -> BQ sdt2 Trp ---GCAAGAAGAGTA 18 AGAGAGCTGGGGGAA---GGTGTGAGCCCGGT- 15 GAA--TGGGCTTGCGA -> EF yusC Met ----AAAGAAGAGTA 18 AGAGAGCCCTGTTT----GCTGAGAATGGG--- 16 GAAG-ATGGTCTTTGA -> CA yhaG Trp ----AAGGAAGAGTA 18 AGAGAGCTGAGGGT----GGTGTGATCTCAGT- 15 GAA--TGGACCTTTTA -> BQ brnQ Ile ----GAGAACGAGTA 19 AGAGAGTTGGCGATTT--GCTGAAAGCCAAC-- 15 GAAA-ATCATCTCCGA -> REF01723 His --TTAGGACATAGTA 18 AGAGACTTTTTCATTG--GCTGAAAGAAAAAG- 17 -----CACACCTAAAA -> BS yvbW Leu -----GGGAGCAGTA 18 AGAGAGCTGCGGGGT---GGTGCGACGCAGC-- 13 GAA--CTCGCCCGGGA ->
Aminoacyl-tRNA synthetases
Amino acid biosynthetic genes
Amino acid transporters
… continued (in the 5’ direction) anti-anti (specifier) codon
Why T-boxes?
• May be easily identified• In most cases functional specificity
may be reliably predicted by the analysis of the specifier codons (anti-anti-codons)
• Sufficiently long to retain phylogenetic signal
=> T-boxes are a good model of regulatory evolution
805 T-boxes in 96 bacteria• Firmicutes
– aa-tRNA synthetases– enzymes– transporters– all amino acids excluding glutamate
• Actinobacteria (regulation of translation – predicted) – branched chain (ileS)– aromatic (Atopobium minutum)
• Delta-proteobacteria – branched chain (leu – enzymes)
• Thermus/Deinococcus group (aa-tRNA synthases)– branched chain (ileS, valS)– glycine
• Chloroflexi, Dictyoglomi– aromatic (trp – enzymes)– branched chain (ileS)– threonine
Double and partially double T-boxes
• TRP: trp operon (Bacillales, C. beijerincki, D. hafniense)
• TYR: pah (B. cereus)• THR: thrZ (Bacillales);
hom (C. difficile)• ILE: ilv operon (B. cereus)• LEU: leuA (C. thermocellum)
• ILE-LEU: ilvDBNCB-leuACDBA (Desulfotomaculum reducens)
• TRP: trp operon (T. tengcongensis)• PHE: arpLA-pheA (D. reducens, S. wolfei) • PHE: trpXY2 (D. reducens) • PHE: yngI (D. reducens) • TYR: yheL (B. cereus) • SER: serCA (D. hafniense)• THR: thrZ (S. uberis)• THR: brnQ-braB1 (C. thermocellum)• HIS: hisXYZ (Lactobacillales)• ARG: yqiXYZ (C. difficile)
Predicted regulation of translation:
ileS in many Actinobacteria• Instead of the terminator, the sequester
hairpin (hides the translation initiation site)• Same mechanism regulates different
processes – cf. riboswitches
A new type of translational T-boxes in Actinobacteria
• Shorter specifier hairpin• Anti-anti-codon in the “head”
loop, not a bulge loop• A majority of cases (all
except Streptomyces spp.)
Same enzymes – different regulators (common part of the aromatic amino acids biosynthesis pathway)
P H E T Y R
trpE
P E P E 4 P
D A H P
S H IK IM AT E
C H O R IS M AT E
trpDCFBA
tyrA hisC aspB
phhA
aroF
aroI aroE
aroA
aroD
aroB
aroC
aroA pheB aroH
yhaG
T R P
T R P
k in u ren in e p a th w ay
A N T H R A N IL AT E
F O L AT E
pabA pabB
A D C
trpG
TRP trpXYZ
TRP\PHE yocR fam ily
TYR yheL
aro:Regulated by TYR (BC)Regulated by PHE (SW O, DRE, HMO, CH, MTH, CTH)Regulated by TRP (DE, DEH)
cf. E.coli: aroF,G,H: feedback inhibition by TRP, TYR, PHE; transcriptional regulation by TrpR, TyrR
Recent duplications and bursts: ARG-T-box in Clostridium difficile
LJ_ARGS
LME_ARGS
LR_ARGS
LP_ARGS
CBE_ARGS
CPE_ARGSCB_ARGS
CTC_ARGS
CAC_ARGS
CDF_YQIXYZ
RDF02391
СDF_ARGC
CDF_ARGH
BC_ARGS2EF_ARGS
BH_ARGS
LSA_ARGSPPE_ARGS
LGA_ARGS
Bacillales
argSyqiXYZ
RDF02391
argCJBDF
predictedamino acidtransporters
NEW
argG
argH
Clostridiumdifficile
amino acidbiosynthetic genes
: ARG-specific T-box regulatory site
aminoacyl-tRNA synthetase
biosynthetic genes
amino acid transporters
NEW
Lactobacillales Clostridiales
argS argS
others
… caused by loss of transcription factor AhrC
Expansion of T-box regulon
regulation of expression of arginine biosynthetic and transport genes by T-box antitermination
: ARG-specific T-box regulatory site
Binding to 5’ UTR gene region regulation of gene expression
Other clostridia spp. (CA, CTC, CTH, CPE, CB, CPE)
yqiXYZ
argC
argH
yqiXYZ
argC
argG
argH
AhrC regulatory protein (negative regulation of arginine metabolism positive regulation of arginine catabolism)
...AhrC site
: AhrC binding site
Gram+ bacteria: Clostridiumdifficile:
AhrC is lost
5’
Duplications and changes in specificity: ASN/ASP/HIS T-boxes
CB_ASNS2
CDF_ASNA
EF_HISS
EX_HISS
BCL_HISSBH_HISS
OB_HISS
BC_HISS
TTE_HISS
DRE_HISS
CH_HISSCTH_HISS
PL_HISS
BE_HISSBL_HISS
BS_HISS
LME_HISXYZCDF_HISZX
LRE_HISXYZLSA_HISXYZ
OOE_HISXYZ
LP_HISXYZ
SGO_HISC
SMU_HISC
EF_HISXYZ
LMO_HISXYZ
EF_HISXYZ
LME_HIS(Z G\ )
LL_HISCLP_HISZ
LCA_HISZCB_ASNS3
CAC_ASNS32
BC_ASNS2
PPE_HISXYZ
PPE_ASNS
LB_ASNA
LD_ASNALJ_ QHMPgln
LJ_ASNA
PPE_ASNALP_ASNA
EX_ASNA
LB_ASNS2
CTC_ASNS2
PPE_HISSLP_HISS
LB_HISS
LJ_HISS
LRE_HISS
LRE_ASPS
LCA_HISS
CPE_ASNA
BC_ASNACBE_ASNS2
CTC_ASNACDF_ASNS2
CPE_ASNS2
his operon
his XYZ
Lactobacilla les
NEW
hisS
Other Gram +
ASP\ASN
HIS
Bacillales
HIS
aspS
SMU_ASPS2SG_ASPS2glnQHMP
L. johnsoniiasnA
ASP
ASN
asnAASN
Lac acillalestobasnS
ASN
aspS
hisXYZ
P. pentosaceus
asnS
HIS
ASP
Clostridiales
asnAASN
ASN
asnA
asnS
asnA
ASP
Rapid m utation of regulatory codons
ASN
AACGAC
hisSASP
Lac acillalestob
HIS
ASPhisS
L. reuteriaspS
ASN
ASN
ASN
ASN
Blow-up 1
PPE_ASNS2
LB_ASNA
LD_ASNALJ_GLNQHMP
LJ_ASNA
PPE_ASNALP_ASNA
PPE_HISSLP_HISS
LB_HISS
LJ_HISS
LRE_HISS
LRE_ASPS
LCA_HISS
aspShisSASP
Lac acillalestob
HIS ASPhisS
L. reuteri
aspS
ASP HIS
CACGAC
asnAASN
Lac acillalestob
disruption of hisS-aspS operonmutation of regulatory codon
L. johnsonii
asnA
ASP
ASN
glnQHMP
PPE_HISXYZ
ASN
AAC
P. pentosaceus
HIS
ASPhisXYZ
asnS
HIS
CAC
ASPASN
AAC GAC
Blow-up 2. Prediction
Regulators lost in lineages with expanded HIS-T-box regulon??
… and validation• conserved motifs upstream of HIS biosynthesis genes
• candidate transcription factor yerC co-localized with the his genes• present only in genomes with the motifs upstream of the his genes• genomes with neither YerC motif nor HIS-T-boxes: attenuators
Bacillales (his operon)
Clostridiales
Thermoanaerobacteriales
Halanaerobiales
Bacillales
New histidine transporters
hisXYZ (The ATP-binding Cassette (ABC) Superfamily)Firmicutes
yuiF (Na+/H+ antiporter, NahC family)Bacillales, some Clostridiales(regulated by his-attenuator in Haemophilus inlfuenzae)
Cphy_3090 (SSS sodium solute transporter superfamily)Clostridiales, Thermoanaerobacteriales, Halanaerobiales
The evolutionary history of the his genes regulation in the Firmicutes
More duplications: THR-T-box in C. difficile and B. cereus
MMY_THRS
OOE_THRS
HMO_YNGICAC_THRZ
BC_THRZ*
BC_THRZ
BC_HOM
BH_THRS
BE_THRSBCE_BRNQ2
BC_THRS
BL_THRZ
BCL_THRZ*
BS_THRZ*
BCL_THRZ
BS_THRZ
BL_THRSBS_THRS
BCL_THRSLMO_THRS
LB_THRSPPE_THRS
LJ_THRS
LP_THRS
TR_THRZ
EX_THRS
CBE_THRZ CTH_THRZCPE_THRS
TTE_THRZ
CDF_THRZ
CDF_HOMCDF_THRC
CDF_HOM*
С _THRZBCTE_THRZ
CBE_THRS
CTC_BRNQ1
LL_THRS
SUI_THRS
STH_THRS
SG_THRS
SMI_THRSSPN_THRS
SMU_THRSSAG_THRSSUB_THRS
SEQ_THRSSPY_THRS
SA_THRS
LME_THRS
MFL_THRS
: THR-specific T-box regulatory site
Bacillales
Clostridiales
LactobacillaceaeLeuconostocaceae
thrS
hom
thrS
thrZ
hom
thrS
thrZ
thrCB
С. difficile
hom
thrS
thrZ
brnQ
hom
thrS
thrZ
brnQB. cereus
brnQ
thrS
thrZ
thrS
thrZ
others
aminoacyl-tRNA synthetase
biosynthetic genes
amino acid transporters
Streptococcaecae
thrCB
Duplications and changes in specificity: branched-chain amino acids
DG_VALS EX_VALS BCL_VALS
CTH_VALS
BC_VALS
BH_VALSBE_VALS
CH_VALS LMO_VALS
CA_ILVC
SA_VALS
OOE_LEUS
PPE_LEUS
LB_LEUS EF_LEUS
LJ_LEUSLGA_LEUS
OB_ILVB
LP_LEUS
LSA_LEUS
OB_LEUSSW O_029_0008
SWO_LEUS BS_YVBW
BL_YVBW
DRE_070_0004CH_LEUS
LM
O_L
EU
S
BL_LEUS
BS_LEUS
BE_LEUSBH_LEUS
BC_LEUS
BCL_LEUS
DTH_ILVB
BS_ILVB
PL_ILVB
BH_ILVB
BE_ILVBBL_ILVB
BCL_ILVB
GSU_LEUA
DH
A_L
EU
A
TTE_LEUS
CTH_148_0001
DF_LEUS
CDF_LEUA
CPE_LEUS
CBE_LEUS
CTC_LEUS
CB_LEUSCA_LEUS
EX_LEUS
DAC_LEUA
BC_YOCR3
OB1271
LP3666
STH_ILES
LP_BRNQ1_ile
SUB_ILES
LL_ILES
LCR_ILES
SPY_ILES
SZ_ILES
SEQ_ILES
SAG_ILES
SMU_ILES
SOB_ILES SMI_ILESSP_ILES
SG_ILES
EF_ILES LME_ILES
LJ_ILES
LD_ILES SA_ILES
LB_ILES
OOE_LP3666LRE_PANE
LP_BRNQ2_val
LCA_BRNQ1_val
LCA_BRNQ2_ileLRE_BRNQ _ile
LJ_BRNQ _ile
LSA_ILES
LJ_OPP
CTC_ILES
CB_ILES
CPE_ILES
TTE_ILES
PPE_ILES
LRE_3666_1
LMO_ILES
DF_ILES
EX_ILES
BC_ILES
BS_ILESBL_ILES
BH_ILES
BCL_ILES
OOE_ILES
DRE_ILVD*_leu
DRE_ILVD _ile
CH_YBGE
BC_ILVB
BE_ILES
DRE_ILES
HMO_ILES
CH_ILES
LRE_3666_2
DHA_ILES
OB_ILES
CTC_BRNQ2CPE_BRNQ
CDF_ILVCCTC_BRNQ1
CAC_BRNQ
BC_ILES2
BCE_BRNQ1
LP_ILES
CTH_ILESLR_LEUS
HMO_ILVB
BC_YBGE*BC_YBGE
DF_VALS
CB_VALS
CBE_VALS
CAC_VALS
CTC_VALS
LL_VALSLCR_VALS LR_VALS
LP_VALS
LSA_VALS
LME_VALS
EF_VALS
PPE_VALS
LD_VALS
LJ_VALS
CPE_VALS
DHA_VALS
BS_VALS
BL_VALS
DRE_VALS
TTE_VALS
HMO_VALS
LEU
VAL ILE
valSVAL
leuSLEU
Firmicutes
Ilv operon
LEU
Bacillales
.......
leu operon
LEU
δ-proteobacteriaClostridium difficileDesulfitobacteriumhafniense
.......
148_0001
LEU
C therm ocellum.
029_0008
LEU
Syntrophom onaswolfei
yvbW
LEU
B. Subtilis.B licheniform is
YOCR3
LEU
B. cereus
OB1271
LEU
Oceanobacillusiheyensis
C acetobutylicum .ilvC
VAL
FirmicutesileS
ILE
LactobacillaceaeClostridiaceaeBacillus cereus
brnQILE
Firmicutes
Lactobacillus casei Lactobacillus plantarum
brnQ
VAL
Ilv operon
LEU
Desulfotomaculum reducens
.......
IlvBN
ILE
Heliobacillus mobilis
Ilv operon2
ILE.......
Ilv operon
ILE
Carboxydothermushydrogenoformans
.......
IlvCB
ILE
.C difficile
ILE
ILE
Recent T-box duplication and mutation of regulatory codon
LEU
ATCCTC
lp3666
ILE
Lactobacillales
opp
ILE
Lactobacillus johnsonii
panE
ILE
Lactobacillus reuteri
Ilv operon2
ILE.......
B. cereus
ILE VAL
GTCCTC
T-box duplication and mutation of regulatory codon
ATC
ATC CTC
Blow-up
transporter:
dual regulation of common enzymes:
ATC CTC
ATC GTC
Three regulator
y systems for the
methionine bio-
synthesis
A. SAM-dependent riboswitch
B. Met-T-boxC. MtaR:
repressor of transcription
MtaR
Methionine regulatory systems: loss of S-box regulons
• S-boxes (SAM-1 riboswitch)– Bacillales– Clostridiales– the Zoo:
• Petrotoga
• actinobacteria (Streptomyces, Thermobifida)
• Chlorobium, Chloroflexus, Cytophaga
• Fusobacterium
• Deinococcus
• proteobacteria (Xanthomonas, Geobacter)
• Met-T-boxes (Met-tRNA-dependent attenuator) + SAM-2 riboswitch for metK– Lactobacillales
• candidate TF-binding motif: MtaR– Streptococcales
Lact. Strep. Bac. Clostr.
ZOO
Summary / History
Acknowledgements
• Alexei Vitreschak
• Andrei Mironov (software)
• Galina Kovaleva (methionine)
• Dmitry Rodionov, Burnham (early work on methionine and S-boxes)
• HHMI• RFBR• RAS (program
“Molecular and Cellular Biology”)
top related