Kassen 2: Selection and Adaptation

Fuck my chungus life

Why does natural selection happen?

Replication on hereditary material is imprecise and so generates genetic variation

Some genetic variants replicate faster than others

Faster replicating lineages contribute more to the next generation

Evolution through selection

Dynamics of an allele under selection

Change in frequency (p) is slowest when p ~0 or 1

Dynamics of substitution (going from from p~0 to 1) follows an S-shaped curve

Time scale of changes on the order of hundreds of generations

Small fitness differences can have a big impact

Selective sweep

A beneficial allele rising from rare and coming to dominate the entire population

Genetic hitchhiking

In asexual populations, a selective sweep will carry linked mutations along with it

Implications of hitchhiking

We cannot be sure that any give mutation we uncover is the cause of selection

• We need additional information

Evolutionary parameters for macrobes

N ~ 10² - 10⁵

Often diploid

Obligatory sexual reproduction

Multicellular

Long generation times

High standing variation

Negligible mutation

Large genome (<1 Gb) with complicated architecture

Evolutionary parameters for microbes

N ~ 10⁵ - 10⁹

Usually haploid

Asexual or facultative sexual reproduction

Unicellular

Short generation times

Low standing variation

High mutation

Smaller genomes (Kb-Mb) with simpler architecture

4 mechanisms that govern the fate of variation in mutation-driven adaptation

1. Mutation supply rate

2. Drift

3. Clonal interference

4. Selection

Mutation supply rate

How many mutations are introduced to the population each generation

NU_b

• U_b = genome-wide mutation rate to beneficial mutation

• The larger the population (N) the more mutations

Drift

Random fluctuations in allele frequencies in finite populations

A beneficial mutation is rare, so could be lost to drift

Probability a beneficial mutation does escape drift

~2s

s= selection coefficient

Clonal interference

Competition from independently arising beneficial mutations

Happens in large populations (NU_b »»»1)

“Wastes” beneficial mutations and slows the rate of adaptations

Also known as the traveling wave

SSSM (Strong Selection, Strong Mutation)

Periodic selection

When NU_b < 1

SSWM (Strong Selection, Weak Mutation)

Selection

Causes fixation or loss of variation

Rate of substitution depends on s and N

Only selection can generate adaptation

Rate of substitution formula

t_fix ~ ½NU_bs + 2lnN/S

What happens to mutations after they arise?

Initially rare, so fate is determined by fitnes

What happens to deleterious mutations after they arise?

Will be lost

What happens to neutral mutations after they arise?

Subject to drift

What happens to beneficial mutations after they arise?

Initial drift (N < 1/s) until selection can take over (N>1/s)

Mutations in large populations

Tend to fix in cohorts

Some neutral or deleterious mutations may hitchhike

How does recombination impact mutations on the same genome?

Unlinks them

Sexual lineages can evolve more quickly as a result

Adaptation

“Fit” between an organism and its environment

Fitness

Genetic contribution of a lineage to the next generation

Absolute fitness

W_i

Rate of replication

Proxies for absolute fitness

Growth rate, number of offspring produced, survival

Relative fitness

w_i

W_i scaled by some standard

In experimental evolution, w_i = W_i/ W_ancestor

Large w_i means more adaptation occurs relative to the common ancestor

Direct measure of fitness using microbes

Complete ancestral and evolved phenotype that have been genetically marked to distinguish phenotype

p = frequency of evolved type

q = 1- p = frequency of ancestral type

Two steps of the unit process of adaptation

1. Genetic variation in introduced or redistributed (via recombination)

2. Selection sorts among extant variants, preserving the type with the highest rate of replication

Genetic variation is the“fuel” and selection is the “engine”

This unit process is repeated many times - adaptations evolve through successive changes

Protein space is a representation of a fitness landscape

Multiple paths to one peak

Can get stuck on one peak even if it’s not the best

• Contingencies (i.e. the human eye)

Mutations - general vibes

Changes to genetic sequence resulting from errors in replication

Undirected, just happen because

Mutation accumulation experiment

Allow us to study the properties of mutation

Repeated bottlenecking to a single individual prevents selection and allows mutations to accumulate

Genome-wide mutation rate

U = # of mutations / # of generations

Per base pair mutation rate

u = U_genome / genome size

Mutation rate in Pseudomonas aeruginosa

1.29 base pair mutations (BPMs) on average in each evolved population

• U = 5.18 × 10 ^-4 BPMs per genome per generation

• u = 7.92 × 10^-11 BPMs per nucleotide per generation

Distribution of fitness effects among mutations

Most mutations are deleterious

A few are neutral or nearly neutral

Even fewer are beneficial

U_b= ~ 8 × 10^-11 mutations per genome per mutation

• U_all = 5 × 10^-4 mutations per genome per generation