Evolution of bacterial regulatory systems

1
Evolution of bacterial regulatory systems

• Mikhail Gelfand
• Institute for Information Transmission Problems,
  RAS
• BGRS-2004, Novosibirsk

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Early analyses (BGRS98, 00, 02)

• Making good predictions with bad rules
• Basic assumption regulons are conserved gt
• Consistency check sites upstream of orthologous
  genes are correct false positives are scattered
  at random
• Validation of individual sites
• Validation of signals candidate signals for
  orthologous factors are correct if similar

3
Multiple genomes taxon-specific
regulation multiple interacting systems
evolution of regulation

• Evolution of orthologous regulatory sites
• Co-evolution of transcription factors and their
  binding signals
• Evolution of regulons (sets of co-regulated
  genes)
• Evolution of regulatory systems

4
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• A list of some observations. In a corner, its
  warm.
• A glance leaves an imprint on anything its dwelt
  on.
• Water is glasss most public form.
• Man is more frightening than its skeleton.
• Joseph Brodsky

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Conservation of non-consensus positions in
orthologous sites
regulatory site LexA ? lexAconsensus nucleotides
are in caps
wrong consensus?
6
PurR ? purL
PurR ? purM
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Non-consensus positions are more conserved than
synonymous codon positions
8
Non-consensus positions may be more conserved
than consensus positions
9
Regulators and their signals

• Subtle changes at close evolutionary distances
• Changes in spacing / geometry of dimers
• Correlation between contacting nucleotides and
  amino acid residues
• Cases of conservation at surprisingly large
  distances

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Zinc repressors
nZUR-?
nZUR-?
GAAATGTTATANTATAACATTTC
GATATGTTATAACATATC
GTAATGTAATAACATTAC
TTAACYRGTTAA
AdcR
pZUR
TAAATCGTAATNATTACGATTTA
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Alignment of nZUR binding signals

• GTAATGTAA TAACATTAC (alpha most genera)
• GATATGTTA TAACATATC (alpha Rhodobacter)
• GAAATGTTATANTATAACATTTC (gamma)
• GaaATGTtA-----TAACATttC (consensus of consensi)

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CRP/FNR family of regulators
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Correlation between contacting nucleotides and
amino acid residues

• CooA in Desulfovibrio spp.
• CRP in Gamma-proteobacteria
• HcpR in Desulfovibrio spp.
• FNR in Gamma-proteobacteria

Contacting residues REnnnR TG 1st arginine GA
glutamate and 2nd arginine
DD COOA ALTTEQLSLHMGATRQTVSTLLNNLVR DV COOA
ELTMEQLAGLVGTTRQTASTLLNDMIR EC CRP
KITRQEIGQIVGCSRETVGRILKMLED YP CRP
KXTRQEIGQIVGCSRETVGRILKMLED VC CRP
KITRQEIGQIVGCSRETVGRILKMLEE DD HCPR
DVSKSLLAGVLGTARETLSRALAKLVE DV HCPR
DVTKGLLAGLLGTARETLSRCLSRMVE EC FNR
TMTRGDIGNYLGLTVETISRLLGRFQK YP FNR
TMTRGDIGNYLGLTVETISRLLGRFQK VC FNR
TMTRGDIGNYLGLTVETISRLLGRFQK
TGTCGGCnnGCCGACA
TTGTGAnnnnnnTCACAA
TTGTgAnnnnnnTcACAA
TTGATnnnnATCAA
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The correlation holds for other factors in the
family
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The LacI family of transcrip-tional regulators
(each branch represents a subfamily)
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and their signals
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BirA regulator of biotin biosynthesis and
transport in eubacteria and archaea
Profile 2 Gram-negative bacteria
Profile 1 Gram-positive bacteria, Archaea
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Evolution of regulons and regulatory systems

• conserved cores
• taxon-specific marginal members
• migration of genes between interacting regulatory
  systems
• taxon-specific cross-regulation
• genome-specific operons and genomic loci
• complete change of regulatory mechanisms

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Genome loci for hyaluronate utilization in
invasive Streptococcus spp.
S. pyogenes, S. agalactiae
S. equi
S. pneumoniae TIGR4
S. pneumoniae R6
S. suis
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Respiration in gamma-proteobacteria1. Three
regulators, different regulatory cascades
Escherichia coli(experimental data)
Haemophilus influenzae, Pasteurella multocida,
A. actinomycetemcomitans
Haemophilus ducreyi, Vibrio spp.
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Respiration in gamma-proteobacteria2. New
genome/taxon-specific regulon members
Escherichia coli (known)
New, non-homologous regulon member
Yersinia pestis Fnr ArcA Yersinia
entercolitica Fnr Pasteurella
multocida Fnr ArcA NarP Actinobacillus
actinomycetemcomitans ArcA NarP Haemophilus
influenzae Fnr ArcA Haemophilus
ducreyi Fnr ArcA NarP Vibrio vulnificus
ArcA Vibrio parahaemolyticus ArcA
Vibrio cholerae Fnr ArcA Vibrio
fischeri ArcA
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Respiration in gamma-proteobacteria3. New
genome/taxon-specific regulon members, contd
Synthesis of molybdate cofactor
Yersinia pestis Fnr Yersinia
entercolitica Fnr ArcA Pasteurella
multocida Fnr ArcA Actinobacillus
actinomycetemcomitans Fnr NarP Haemophilus
influenzae Fnr NarP Haemophilus
ducreyi Fnr ArcA NarP Vibrio vulnificus
NarP Vibrio parahaemolyticus NarP
Vibrio cholerae NarP Vibrio
fischeri ArcA NarP
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Zinc repressors - recapitulation
nZUR-?
nZUR-?
GAAATGTTATANTATAACATTTC
GATATGTTATAACATATC
GTAATGTAATAACATTAC
TTAACYRGTTAA
AdcR
pZUR
TAAATCGTAATNATTACGATTTA
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Five regulatory systems for methionine
biosynthesis

• SAM-dependent RNA riboswitch
• Met-tRNA-dependent T-box (RNA)
• C,D,E. repressors of transcription

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Three methionine regulatory systems in
Gram-positive bacteria loss of S-box regulons

• S-boxes (riboswitch)
• Bacillales
• Clostridiales
• the Zoo
• Petrotoga
• actinobacteria (Streptomyces, Thermobifida)
• Chlorobium, Chloroflexus, Cytophaga
• Fusobacterium
• Deinococcus
• proteobacteria (Xanthomonas, Geobacter)
• Met-T-boxes (Met-tRNA-dependent attenuator)
• Lactobacillales
• MET-boxes (candidate transcription signal)
• Streptococcales

ZOO
Lact.
Strep.
Bac.
Clostr.
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Catabolism of gluconate in proteobacteria
27
Three regulatory systemsone global (FruR), two
taxon-specific (GntR, PtxS)
ß
?1
Pseudomonas spp.
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Instead of conclusions

• Andrei A. Mironov (BGRS98,00,02,04)
• Anna Gerasimova (BGRS02,04)
• Olga Kalinina (BGRS02,04)
• Alexei Kazakov (BGRS02,04)
• Ekaterina Kotelnikova (BGRS02,04)
• Galina Kovaleva (BGRS04)
• Pavel Novichkov (BGRS00,02,04)
• Olga Laikova (BGRS02,04)
• Ekaterina Panina (BGRS00)(now at UCLA, USA)
• Elizabeth Permina (BGRS02,04)
• Dmitry Ravcheev (BGRS02,04)
• Alexandra B. Rakhmaninova (BGRS00)
• Dmitry Rodionov (BGRS00)
• Alexey Vitreschak (BGRS00,04)(visiting LORIA,
  France)

• Howard Hughes Medical Institute
• Ludwig Institute of Cancer Research
• Russian Fund of Basic Research
• Programs Origin and Evolution of the Biosphere
  and Molecular and Cellular Biology, Russian
  Academy of Sciences