Role of mutator in adaptive evolution

Inferred horizontal transfers in mutS gene

Denamur Cell (2000)

Taddei PNAS 1995Bjedov Science 2003

Taddei Nature 1997Matic Science 1997Giraud Science 2001

Conflicts between replicators as causes of individuals death

Molecules vs cellule eg prion, aggregate Cellular vs multi-cellular eg cancer Individual vs society eg nihilism, wars Idea vs individual eg suicide

vertical transmission --> mutualism/interests aligned

horizontal transmission --> parasitism/conflict

For phenotype to depend only genotype and environment

One must take into account DNA extended environment

intracellular environment is

dynamic, & local & heritable

The extended phenotype allows the organisms to modify their niche,adapting their environmentrather than adapting to it

Via ecological inheritancetheir offspring can inheritthe modified niche

Cultural inheritance in animals

Science July 23 2004

Ideas can propagate like epidemics(suicide, collective hysteria, rumors, fashion, cooperation…)

Their propagation is mediated by contacts(oral, print, radio, TV, internet…)

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Do ideas change by darwinian-like dynamics ?

Variability re-combination, mutation, migrationOptimal rates ?

Selectioncoherence with the intellectual ecosystemPasteur : « chance favors the prepared mind »

Transmission stability, emission / reception

Knowledge about the environment can be

learned by 4 Darwinian heuristics

1 genetic2 individual learning3 social learning / culture4 science

Common characteritics

variabilityselection retention/transmission

Conservatism: the tragedy of Semmelweis

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The difficulties of Pasteur & Fleming

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From parasitic cuckoos to vaccination : Jenner

Evolutionary fate of ideas Properties of ideas

Simplicity, genericity, predictibility, compatibility, robustness, stability (what are their optimal characterisitics to appear and propagate ?)

Properties of their environmentWhat are the constraints that affect idea generation and propagation ? (social/genetical/historical/ emotional/ individual/media…)

Interactions ideas / environmentSymbiosis between individuals, societies, genes, ideas (Conflicts and alliances may lead to exploitation or mutualism)

Sym-bio-sisAssociation of entities of interests that Diverge (exploitation eg parasites) Converge (mutualism)

vertical transmission favors mutualism/control horizontal transmission favors parasitism/no control

Dangerous liaisons passage from one to the other via

Mutationenvironmental contextthird party (eg the enemy of my enemy…)

The Smallpox Wars

1519: Cortez & 5000 soldiers plus unintentional smallpox

(Destroyed Aztec Empire in 2 years, reduced native population from 30 to 3M in a half century) From Historia De Las Casas de Nueva Espana, Volume

4, Book 12, Lam. cliii, plate 114.

Smallpox attacks on Native Americans

1763: Lord Amherst and the smallpox blankets(ordered blankets to be taken from smallpox patients and given to Delaware Indians at a peace-making parley)

1957-65: Brazilian speculators & the Indian Protective Service(introduced smallpox via infected fabrics, and measles, flu and TB via contact with ill whites)

Bacteriophage lambda life cycle

99 %

100 / infected bacteria 10-4 without external stress

1%

Lysogenic strains are immune against surinfection

High frequency of lambdoids within E. coli genomes

Causes of spontaneous deaths in E. coli

stochastic effects(e.g. membrane disruption)

clonal death (e.g. the 4 grand-daughters of one cell)

aging-associated deaths(old pole effect)

Accumulation of intra-cellular parasite ?(e.g. autocatalytic protein aggregates, prions ?)

Programmed deaths(e.g. colicin or prophage induction in sick cells)

Can death of individuals be selected for ?

Death can benefit kins if it frees them of

> parasites (suicide of infected cells)Cells infected by viruses kill themselves preventing the release of viruses that could kill their kins

> accumulated defects (aged components segregated to old poles)The mother cells keeping all the problem for itself to give its progeny a fresh start (~ germ line)

> The cost of perfect maintenanceMaintenance has diminishing returns

> competitors if the dying cells release chemical or biological weapon that kill the competitor while sparing the kins

Can parasite induced death be beneficial ?

Lysogenic phage effects :

Prophage presence is costly for hosts (pleiotropic effects on all + death of induced cells)

Classical Parasitic effects (direct)

Biological weapons against competitors (mutualistic indirect effects) ?

C S

1 phage production induced in a sub-population of dying carrier C

P1 3

3 New phages P are released upon competitors death

2

2 Infection of susceptible cells S

Amplification of phage ‘weapon’

X

models of weapon-mediated competition

dC/dt = r(1-(C+S)/k)C dS/dt = r(1-(C+S)/k)S

+ y a V Sy

SC r,k

Design model of parasite-mediated competitionMeasure direct-effect parameters in the labSimulate indirect competitive consequencesReturn to lab to conduct competition experimentsContrast with colicin-competition

- x C- a V S

Vx

adV/dt = x y C - V (u +aN )

Biological weapons allow victories of their hoststhat are even faster with carrier’s rarity

Experiments Simulations

Competition between phage carriers ( C ) and susceptibles (S) (with different initial ratio 1/100, 1/1, 100/1)

Brown & Le chat

Contrary to colicin-carrier, in unstructured EPhage carrier can invade even when rare

0 2́ 107 4́ 107 6́ 107 8́ 107 1́ 1080

5

10

15

20

Carrying capacity, k

Burst

size,

y

S wins

C and CS

win (phage)C or S win(colicin)

11%

100%

15%

25%

45%

COLICIN: C and S are both stable against invasion when aky > u

The winner depends on intial conditions (in a well-mixed system)

C cannot invade when rare

PHAGE: carriers ALWAYS win when aky > u

Aky=u

k

y

public goods dilemmas

Public goods are collectively constructed resources of use to all - Microbes, like humans, struggle with public goods.

Defining elements of societies – shelter, accesible resources, defence, information

Public goods present dilemmas because of the temptation to cheat

Time

Colicin = linear weaponCarrier win in structured environment

Invaders arrivalamong residents

Local changeLocal deathLocal invader expansion

Invader victory

but cannot invade unstructured environment when rare as effort is diluted

Time

Invader expansion inempty niche

Invader arrivalTrigger change

AutocatalyticchangeLead to fastNiche emptyingwave

Invader expansion inempty niche

Virus = fireAutocatalytic weaponallow invasion in all environments even if carrier is rare

Fast and globalenvironment modification

Invader arrivalTrigger change

unstructuredstructured

Phages as motor of genomic diversity in E. coli O157

Ohnishi PNAS. 2002

Hendrix Trends Microbiol. 2000

Lambdoids carry a variety of genes affecting bacterial phenotypes

Shiga-toxin induction in vivo

Zhang J. Infect. Dis. 2000

Waldor Trends Microbiol. 1998

Shiga-like toxins expression is controled by lambdoid phages

1 phage production induced in a sub-population of carrier C

2 Infection of susceptible cells S.

3 New phages P are released upon competitors death

4 Toxins are released together with phages

5 Toxins trigger non specific host immune response

6 Host response empty the niche from other competitors (while phage carrier C are protected by virulence factors)

Niche emptying by virus and toxin :or why commensals should carry virulence factors

C S

P1 2

3

Toxin

Host response

Competitors

4

5

6

Deteriorating ones environment (us!) can pay to eliminate competitors

Changing the rule of the game

C

E > 0

R?

E = 0

Unmodified Environment (E = 0) favours the residents, R Modified Environment (E >0) can favour invaders, C

Thus C can only invade R by modifying the shared environment

C = “proactive invaders”

R = susceptible residents

E = environmental dimension (virus/toxin/fire…)

Public goods can be good or bad

• The absolute effect of modified can favour both C and R (b>0), or neither (b<0)

• When g=0, R is resistant to invasion by rare C

• When g=q, R invasible by rare C if d j < x, ie if

• the cost of innovation (x) is small• the market for innovation (j) is large• the differential of adaptation (d) is

large

• DOESN’T MATTER IF THE INNOVATION IS GOOD OR BAD!

• (unless so bad that neither C nor R can survive)

RC

Ex

r,k

g,q,j

b,d b

dC/dt = r(1-N/k)C- x C + (b+d) C EdR/dt = r(1-N/k)R + b R EdE/dt = x C + g E – q (E/j) E

When genotypes adapt their environment

Invaders not preadapted to an environment can succeed if

1) They can modify the environment at low enough cost

2) the modification benefit them more than the resident

This can happen if

- the invaders are numerous enough

- the environment is structured (slow)

- or if the environmental change is autocatalytic (fast)

Examples of autocatalytical change include the spread of

bioweapon, fire, farming, cultural or technological innovations

From lucky invaders to proactive invadersCoevolution of genotype & environmental perturbation

then it pays to select for genes (symbionts) increasing EP(eg manipulating host response or increasing fire),Thus creating a positive feedback loop leading to selection for

proactive invaders = niche modifiers

If by chance a genotype is better adapted toenvironmental perturbation (EP) = lucky invader

If EP are frequent, selection for more EP resistant genes(eg resist inflammation or fire resistance) = recurrent invader

DNA extended phenotype & niche construction

Genes extended phenotype (eg spider web) are not limited to the organism boundary

Genes can modify not only the environment of DNA and cells but also of organisms

As via development DNA lead to organism construction, it can also lead to niche construction

Through its environmental, technological and cultural modifications,

niche can be heritable (eg nest, beaver dam, tool use) leading to

ecological inheritance and extended heritability

How do genes, environment and ideas co-evolve ?(eg lactose tolerance, domestic mammals, indo european languages and farming)

Rare proactive invaders initiate self-propagating environmental change to replace fit residents

Sam Brown, Ludo Le Chat, François Taddei