What is the evidence

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What is the evidence for horizontal transmission
of host genes by viruses?
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dUTPase
dUTP
dUMP

2 Pi

• What is dUTPase?
• Deoxyuridine triphosphatase converts dUTP into
  dUMP.
• Why is dUTPase important?
• Excessive amounts of dUTP cause the incorporation
  of uracil into growing DNA chains.
• All organisms examined to date possess a UNG to
  excise dUTP misincorporated into DNA.
• In the presence of a large dUTP pool UNG repair
  causes DNA strand breakage, which can lead to
  cell death.

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Questions regarding dUTPase

• What is the relationship, and distribution of
  dUTPase in viruses, eukaryotes, eubacteria, and
  archaea?
• Is the genome location of dUTPase conserved?
• What kinds of motif arrangements exist?
• How might these arrangements assemble?

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Three observed types of Motif Arrangements
single gene copy one ordered-series-of-motifs five
conserved motifs
I II III IV V
amino carboxyl
tandem duplication two ordered-series-of-motifs fi
ve conserved motifs
I II ? IV V
? ? III ? -
amino
middle
carboxyl
tandem triplication three ordered-series-of-motifs
15 conserved motifs
I II III IV V
I II III IV V
I II III IV V
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Representative Sample of dUTPase HMM Alignment
Eukaryotes Eubacteria Archaea Retroviruses Herpesv
iruses Other DNA Viruses
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Retroviruses
pol gene
gag gene
HTLV-like viruses
RSV
PR
other retroviruses
MMTV-like viruses
dUTP
PR
Non-primate Lentiviruses
dUTP
PR
RT
RH
IN
HIV
PR
Herpesviruses ???alpha ???gamma
dUTP
dUTP
RRRP
PMASE
dUTP
dUTP
RRRP
PMASE
Poxviruses Vacinnia Suid Pox
dUTP
TIF
RR
?
?
?
?
?
UH
dUTP
RR
TIF
?
?
UH
Bacteria E. coli P. aeruginosa C.
burnetti
dUTP
?
DSF
dUTP
DSF
PPMM
?
dUTP
PIB
PPMM
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100
81
100
Additive Distance Tree for 90 dUTPase sequences
HSAP
ORFV
VARI
CPOX
100
67
VACW
VACL
SPOX
60
AVAD
CELA
100
CELM
66
CELC
99
LESC
74
CALB
SCER
PBCV
BPT5
69
92
100
Eukaryotes Eubacteria Archaea Retroviruses Herpesv
iruses Other DNA Viruses
96
CTRA
CDIF
100
MTUB
BPRT
100
100
BPSP
MJAN
100
SIRV
DAMB
IHER
SHER
100
97
95
100
80
100
100
100
100
98
MIAP
JSRV
75
100
SARV
83
100
HER1
100
MMTC
100
94
77
100
100
60
100
75
ASFV
ONPH
59
61
HH8A
AH1A
100
EH4A
75
SH1A
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Assembly and Active Site location in H. sapiens
dUTPase
Clifford D. Mol et al (1996) Structure 4(9)
1077-1092
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Hypothesized dUTPase folding and assembly
H. sapiens (single)
Herpes (double)
C. elegans (triple)
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Summary

• dUTPase is found in
• 8 virus families (Retroviruses and DNA viruses)
• Eukaryotes (multicellular and unicellular)
• Eubacteria (Proteobacteria, Firmicutes,
  Chlamydiales, Spirochaetales)
• Archaea
• Three kinds of motif arrangements exist
• (Single, Double, and Triple)
• It is hypothesized these arrangements assemble
• ?, ? Herpesvirus dUTPases (Double) as trimers
• C. elegans dUTPases (Triple) as monomers.
• The genome location of dUTPase is not conserved
  in viruses and eubacteria.
• 6 virus groups have dUTPases similar to those of
  hosts.