in memory of john maynard smith
DESCRIPTION
In memory of John Maynard Smith. Phenotypic variability is omnipresent in nature. It takes all the running you can do to keep in the same place. If you want to get somewhere else, you must run at least twice as fast. Lewis Carroll, 1871. environmentally. intraspecific. induced adaptation. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/1.jpg)
In memory of
John Maynard Smith
![Page 2: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/2.jpg)
Phenotypic variability is omnipresent in nature
![Page 3: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/3.jpg)
It takes all the running you can do to keep in the same place
If you want to get somewhere else, you must run at least twice as fast
Lewis Carroll, 1871
![Page 4: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/4.jpg)
A B A B A B••••• •
intraspecific variability
environmentally induced adaptation
Lamarckian Paradigm
A B A B BA• • • • ••
Darwinian Paradigm
natural selection
natural selection
![Page 5: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/5.jpg)
Darwinian evolution : variability, selection, transmission
time
Num
ber
of c
opie
s
Adaptives mutations : 0 1 2 3 4 5 6
Can be applied to any «amplifiable information» (Dawkins, 1976, « the selfish gene »)
![Page 6: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/6.jpg)
Different types of MUTATIONS
Neutral
Lethal
Deleterious
Adaptives
10 -5
10 -4
10 -8
wildtype
mutS+
Mutator
mutS-
10 -3
10 -2
10 -6
Estimated total mutation rate for bacteria1 mutation / 300 genomes replicated
An invariant in evolution of DNA !? (Drake rule)
![Page 7: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/7.jpg)
Mechanisms controlling the maintenance of genetic information
nucleotide pool
DNA repair
Fidelity of synthesis
post-replication control
![Page 8: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/8.jpg)
Photoactivation Repair in E. coli
• Exposing UV treated cells to blue light results in a reversal of the thymine dimer formation
• Enzyme, photoactivation repair enzyme (PRE) absorbs a photon of light (from blue light) and is able to cleave the bond forming the thymine dimer.
• Once bond is cleaved, DNA is back to normal
![Page 9: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/9.jpg)
Like other repair systemIt is conserved throughout evolution, conserved from bacteria (where first discovered)to man where they are involved in a variety of disease
Excision Repair
![Page 10: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/10.jpg)
Xeroderma Pigmentosum & Nucleotide Excision Repair
• Xeroderma pigmentosum (XP)- is a rare genetic disorder that predisposes an individual to skin abnormalities
– Individuals lose the ability to undergo NER• UV radiation exposure leads to reactions from freckling and skin
ulceration to skin cancer
– Studies suggest many different genes may be involved in excision repair
– XP-variant is encoding a lesion by-pass DNA polymerase (SOS)
![Page 11: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/11.jpg)
By-pass polymerasescan lead to error free or error prone (mutagenic) synthesis depending on the lesion
![Page 12: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/12.jpg)
Oxidation of guanine lead to transversion
![Page 13: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/13.jpg)
The Mismatch Repair System
ExoI, ExoVII, RecJ, UvrD, PolIII, SSB, Ligase
CH3
MutSMutL
CH3
MutH
Mismatch repair system• corrects replication errors • ensures global genomic stability • prevent tumour formation
Mismatch site
GATC-site
![Page 14: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/14.jpg)
High polymorphism of mutation rates in commensal and pathogenic Escherichia coli natural isolates
7060 6550 5540 4530 3525201510501E-9
1E-8
1E-7
1E-6
1E-5
Frequency of mutations to Rif in mutator strains
Strain number
mutS-
mutS-
mutL-
mutL-
R
Commensals FranceCommensals MaliCommensals Croatia
UTIbacteremiapusneonatal meningitis
haemolytic-uremicsyndrome
I. Matic, M. Radman, F. Taddei, B. Picard, C. Doit, E. Bingen, E. Denamur and J. ElionScience (1997) vol. 277 p. 1833
mutS-
![Page 15: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/15.jpg)
The frequencies of mutator among E. coli vary
with the associated pathologies
Denamur J. bacteriol. 2002
![Page 16: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/16.jpg)
Number of virulence factors correlates with in vivo virulence
Picard Infect.Immun. 2001
only in non-mutator strains
![Page 17: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/17.jpg)
Mutation rates are higher among strains with
intermediate virulence
Picard Infect.Immun. 2001
![Page 18: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/18.jpg)
![Page 19: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/19.jpg)
1E-05
1E-04
1E-03
1E-02
1E-01
1E+00
0 5000 10000 15000
Temps (générations)
Modélisation des mutateurs
Nature (1997) 387 700-702
Time (generations)
Mut
ator
fre
quen
cyModelling mutators frequencies during adaptation to a new environment
![Page 20: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/20.jpg)
Tenaillon Genetics (1999)
Selecting for mutators is easier in larger population
![Page 21: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/21.jpg)
Tenaillon Genetics (1999)
When mutation is rate limiting large population adapt much faster
log (population size)
![Page 22: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/22.jpg)
Tenaillon Genetics (1999)
Mutator can speed up adaptation (even when rare)
log (population size)
![Page 23: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/23.jpg)
Kiss meI ’m germ-
free
An in vivo model: an animal with a controled microbial flora
Giraud
![Page 24: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/24.jpg)
Evolution of population size
mutS+
days
log
(pop
ulat
ion
size
)8,8
9,0
9,2
9,4
9,6
9,8
10,0
10,2
0 5 10 15 20
mutS+
mutS- mutS-
Mutator bacteria adapt faster to a new environment
Giraud Science 2001
![Page 25: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/25.jpg)
Time (Days)
Mea
n lo
g(m
utat
or/w
ild t
ype)
0 1 2 3 4 5 6 7 8 9 10
-5
-4
-3
-2
-1
0
1
2
3
4
5
The initial population size influence the outcome of the competition
mutS-/mutS+
mutS-/ 50 mutS+
mutS-/ 50 000 mutS+
Giraud et al Science 2001
![Page 26: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/26.jpg)
The population threshold for mutator victory
is 1/(mutation rate)
Mutator victory threshold is frequency independentLe Chat
![Page 27: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/27.jpg)
The victory is stochastic with a constant expected gain
Le Chat
![Page 28: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/28.jpg)
Once adaptation is achieved the mutator advantage is reduced
Mea
n l
og
(mu
tato
r/w
ild
typ
e)
-1
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
0 1 2 3 4 5 6 7 8 9 10Time (Days)
Naive
adapted
Giraud et al Science 2001
![Page 29: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/29.jpg)
WT+Mut MutWT
Mutators & migration in vivo
-1
0
1
2
3
0 2 4 6 8 10Days
Log
(mut
S- / m
utS+
)
-1
0
1
2
3
0 2 4 6 8 10Days
Log
(mut
S- / m
utS+
)The benefit of the mutator is reduced in presence of migration
![Page 30: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/30.jpg)
Controlling migration timing in vitro
WT Mut
0 12 24
hours
migration
24 h
migration
24 h
media: LB + Spc
Mut : mutS-
15 18 21
V VV V
Le Chat
![Page 31: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/31.jpg)
55,5
66,5
77,5
88,5
99,510
9 12 15 18 21 24
log
(C
FU
)
Mutator population adapt faster
mutator
nonmutator
The benefit of the mutator disappears if adaptation is over before migration
"migration"
-0,5
0
0,5
1
1,5
2
2,5
3
9 12 15 18 21 24lo
g (
mu
tato
r/W
T)
![Page 32: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/32.jpg)
Mutator bacteria suffer from genetic amnesia
mutS- ancestormutS+ ancestor
Days post inoculum
Mean % of auxotrophs
100 150 200 250 3000
510
15
202530
ndnd
Emergingmutator
non mutator
Giraud et al Science 2001
![Page 33: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/33.jpg)
23456789
1011
0 5fos spc
4 mice
10 15
Impact of antibiotic treatments on mutation rates
Log
(po
pula
tion
size
)
20fos spc fos spc
23456789
1011
0 5 10 15 20
1 mouse
2023456789
1011
0 5 10 15
1 mouse
Rpopulation Rif
![Page 34: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/34.jpg)
fosspc
time
Day 0 : inoculation
Measures of population sizes
streptomycinNalidixic acid
23456789
1011
0 5 10 15 20
1 mouse
fos spc20
23456789
1011
0 5 10 15
1 mouse
fos spc
![Page 35: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/35.jpg)
str + nal
Impact of mutation rates on bacterial survival to antibiotic treatments
2
3
4
5
6
7
8
9
1011
0 5 10
Log
( p
opul
atio
n si
ze)
non mutator
mutator
![Page 36: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/36.jpg)
How many antibiotics should be used against mutator bacteria ?
Percentage of treatment failure
Number of antibiotics administered simultaneously
Ancestral genotype1 2 3
Antimutator (mutS+) 100 0 (+17*) n.d.
Mutator (mutS-) n.d. 70 0
*emerging mutator (2 mutS-)
Giraud AAC (2002)
![Page 37: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/37.jpg)
Denamur J. bacteriol. 2002
Mutator bacteria are more likely to become antibiotic resistant
![Page 38: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/38.jpg)
Non mutator (A) and mutator (B) phenotypes on antibiograms
Denamur et al J. bacteriol 2002
![Page 39: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/39.jpg)
Mutators are abundant and more antibiotic resistant among P. aeruginosa infecting Cystic Fibrosis patients
Oliver Science (2000)
Mutator (CF)
Non-mutator (CF)
Non-CF
![Page 40: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/40.jpg)
Resistance accumulate 3 times faster in patients colonised by mutators
MutatorNon mutator
delay (days)
Pro
babi
lity
of
incr
ease
d re
sist
ance
Moumile
![Page 41: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/41.jpg)
Mutator can speed up cellular evolution
time
Cel
l num
ber
time
Cel
l num
ber Mutator sub-population
Adaptives mutations
0 1 2 3 4 5 6
![Page 42: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/42.jpg)
The bacterial Red Queen
![Page 43: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/43.jpg)
Why change ?Population geneticsGodelle Gouyon Brown Maynard-Smith
Change where ?Microbial ecology Fons
Who changes ?Molecular epidemiologyBinguen Denamur Picard Brisabois Berche
A network approach of bacterial variability
GiraudLechatBambou
B. ToupanceO. TenaillonJ-B André
Duriez
Change what?Bio-informaticsRocha
Who has changed ?Molecular PhylogenyLecointre Darlu
How to change ? Molecular biology Matic Radman Vulic Dionisio BjedovBregeon Leroy Hayakawa Sekiguchi Dukan
Change when ?transcriptome analysis Knudsen Cerf
Phenotypic variabilityLife History Stewart Madden Lindner Paul Gabriel Fontaine Depaepe Bredèche Mosser
Moumile
Diard
![Page 44: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/44.jpg)
www.necker.fr/tamara/
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
Join Fun & Science
in Paris
![Page 45: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/45.jpg)
Hyper-recombination phenotypes of
mismatch repair mutants
Denamur Cell (2000)
![Page 46: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/46.jpg)
BB
A
A
Holliday junction
Splice
Patch
+
+
Homologous Recombination
• exchange of DNA 1strands to form heteroduplex DNA
• cleavage of Holliday junction at A or B
• religation to recombinant products
A: splice products B: patch products
![Page 47: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/47.jpg)
The barrier to recombination is DNA sequence divergence
Vulic PNAS (1997)
![Page 48: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/48.jpg)
Holliday junction
Splice
Patch
+
+
Homeologous Recombination
• divergent sequences do not recombine efficiently
• mismatch repair prevents formation of recombination intermediates
• in mismatch repair deficient background homeologous recombination proceeds to generate mosaic genes and genomes
mismatch +mismatch -
![Page 49: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/49.jpg)
Effect of Mismatch Repair System on InterspeciesRecombination
![Page 50: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/50.jpg)
Inhibition of Mismatch Repair System
• increases homeologous recombination to the level of homologous recombination and thus allows interspecies recombination
• allows broadest genetic variability in vivo
• broad area of applications• generation of novel low molecular weight entities• generation of modified and optimised macromolecules• generation of (micro)organisms with desired properties
![Page 51: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/51.jpg)
Homeologous Recombination In Vivo
Mosaic Genes Mosaic Genomes
Mosaic Proteins Mosaic Pathways
A´
D´
B´
C´
A
D
B
CC´´
D´´
Novel Products
![Page 52: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/52.jpg)
The bacterial Red Queen
![Page 53: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/53.jpg)
Why change ?Population geneticsGodelle Gouyon Brown Maynard-Smith
Change where ?Microbial ecology Fons
Who changes ?Molecular epidemiologyBinguen Denamur Picard Brisabois Berche
A network approach of bacterial variability
GiraudLechatBambou
B. ToupanceO. TenaillonJ-B André
Duriez
Change what?Bio-informaticsRocha
Who has changed ?Molecular PhylogenyLecointre Darlu
How to change ? Molecular biology Matic Radman Vulic Dionisio BjedovBregeon Leroy Hayakawa Sekiguchi Dukan
Change when ?transcriptome analysis Knudsen Cerf
Phenotypic variabilityLife History Stewart Madden Lindner Paul Gabriel Fontaine Depaepe Bredèche Mosser
Moumile
Diard
![Page 54: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/54.jpg)
www.necker.fr/tamara/
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
Join Fun & Science
in Paris
![Page 55: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/55.jpg)
Most genes in E. coli genome have a common history
Denamur Cell (2000)
![Page 56: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/56.jpg)
Phylogenetic trees of mismatch repair genes show horizontal transfers
Denamur Cell (2000)
![Page 57: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/57.jpg)
Inferred horizontal transfers in mutU gene
Denamur Cell (2000)
![Page 58: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/58.jpg)
Inferred horizontal transfers in mutS gene
Denamur Cell (2000)
![Page 59: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/59.jpg)
Horizontal transfers are more abundant in mismatch repair genes
Denamur Cell (2000)
![Page 60: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/60.jpg)
Hyper-recombination phenotypes of
mismatch repair mutants
Denamur Cell (2000)
![Page 61: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/61.jpg)
Hyper-rec phenotypes of mutator genes correlate with their sequence mosaicisms
Denamur Cell (2000)
![Page 62: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/62.jpg)
Mutator bacteria suffer from genetic amnesia
mutS- ancestormutS+ ancestor
Days post inoculum
Mean % of auxotrophs
100 150 200 250 3000
510
15
202530
ndnd
Emergingmutator
non mutator
Giraud et al Science 2001
![Page 63: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/63.jpg)
Role of mutator in adaptive evolution
![Page 64: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/64.jpg)
The bacterial Red Queen
![Page 65: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/65.jpg)
Why change ?Population geneticsGodelle Gouyon Brown Maynard-Smith
Change where ?Microbial ecology Fons
Who changes ?Molecular epidemiologyBinguen Denamur Picard Brisabois Berche
A network approach of bacterial variability
GiraudLechatBambou
B. ToupanceO. TenaillonJ-B André
Duriez
Change what?Bio-informaticsRocha
Who has changed ?Molecular PhylogenyLecointre Darlu
How to change ? Molecular biology Matic Radman Vulic Dionisio BjedovBregeon Leroy Hayakawa Sekiguchi Dukan
Change when ?transcriptome analysis Knudsen Cerf
Phenotypic variabilityLife History Stewart Madden Lindner Paul Gabriel Fontaine Depaepe Bredèche Mosser
Moumile
Diard
![Page 66: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/66.jpg)
www.necker.fr/tamara/
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
Join Fun & Science
in Paris
![Page 67: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/67.jpg)
How to adapt to predictable
impredictability ?
![Page 68: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/68.jpg)
start stop
ORF
duplication
deletionconversion
Recombination between close repeats
Recombination between SSR
st art stop
ORF
XXXXXX XXXXXXXX
delet ion
XXXX
duplicat ion
Localized mutators
Rocha Nucleic Acid Research (2002)
x y
x x x
x x y
![Page 69: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/69.jpg)
Close direct repeats
gene500 bp 500 bp
1 2
1 2
1 2
L < 1000 ntObserved
Observed in 1000 random sequences
of equal length and 3-tuple composition
ObservedExpected = 1.9Over-represented classes:
• Recombination, repair• Transcription, RNA degradation
• Translation• Transport proteins
![Page 70: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/70.jpg)
Close direct repeats.
5
10
0 10 20 30Number of close repeats in gene
0
gene500 bp 500 bp
1 2
1 2
1 2
L < 1000 ntStress response
genes
All E. coli K12genes
Rocha NAR (2002)
![Page 71: In memory of John Maynard Smith](https://reader036.vdocuments.net/reader036/viewer/2022081519/568143d5550346895db061b1/html5/thumbnails/71.jpg)
aab
bcccc
dddd e
eff
gg h
hh
hhh
iii
i
jjkk ll
dnaA
position (kb)
a ab b b
b
c c c
cd
d
e
eg
g
h hi
ij
j
k k
l l
m
mn n
o
op p
q
qr rf
f
betB
b
b
c
c c c
c
c
c d de ef
f f
g g
h
h hm m
n
n oop pl
l
k kj
ji
i a a
mutS
a
abb
cc c
d dd d d
d
d de e
csgA
a
a
b
b
c c
d d e ef
f g gh
h
i
i
i
j j
k
k
k
n n n n n q q
p
p
o
o m m l
lmutL
a
a
a
a
a a
a
a
f
f
g g
h
he e
ee
ee
e e
e
e
e
e
e e
e
ed
d
d d dc c b
b baceF
a
a b b b bc
c
c c
c
c
c
c c
f
f g
gm m
p
p p
q
qr rs
su u
v v t t
o oo
n
n
n n
n
ll l lkj j
i
ih
h
e
ed dsbcC
a a
b
b
bc c
c
e e
e
f
f
i iik kl ln no op p
lamB
a a
bc cd dfg h il mnj e
b bcd d df gh i l mo o k kje
cyoE
a
ab
b bc c c c
c
d
d
f fj ji ih hg g
e e
cyoC
a
ab b bc c d d
e
ef fg g
g
i i
h
h
sodB
0
0
0
0
00
0 0
0 0
1
2 4
3
position (kb)0 3
gene
occurrence of the repeat
b repeat label
21 21
21
21
21
21
21 31
1
1
Rocha NAR (2002)