EVE 100 Midterm 2

Dominance

• describes the effect of an allele on a phenotypic character when it is paired with another allele in a heterozygote condition —> higher fitness

• takes longer to reach fixation since the recessive alleles hide in the background

• Advantageous dominant alleles increase in frequency more rapidly since it is expressed in both homozygous and heterozygous genotypes

Recessive alleles

• Hide behind the dominant allele even when advantageous

• advantageous recessive alleles take a long time to increase in frequency since when at lowe frequencies, it is present in the heterozygous form → invisible to selection

• Advantageous recessive alleles can reach fixation since they hide in the background

• After the advantageous dominant allele attains high frequency, the alternative disadvantageous recessive allele is slowly eliminated → rare recessive alleles occur mostly in heterozygous forms -→ invisible to selection

Fitness

• Measure of the “relative success of a population, genotype, and alleles

• measures how often thinsg reproduces

• defined by the probability of survival and the avergae number of offspring

• best applied to a set of entities → all individuals in a population or individuals with a given genotype

• MOST fit genotype = relative fitness of 1

• LEAST fit genotype = relative fitness of 1-s (s = selection coefficient)

• HETEROZYGOUS genotype = relative fitness of 1- hs (h - dominance coefficient) → determines how far the heterozygous genotype is from the homozygous phenotypes

  • h = 0 → A1 is dominant

  • h = 0.5 → A1 is additive

  • h = 1 → A2 would be dominant (A1 is recessive)

Finding relative fitness

• absolute fitness/the highest absolute fitness —> needs to be ain a decimal form less than or equal to 1

Selection coefficient

• finds how fit something is from the MOST fit organism

  • most fit h and s coefficients help us understand how dominance affects fitness

Decent of modification

genetic changes in populations over timeM

Mutations

• Mutation rates per base pair are low —> but the number of new mutations per individual may be large

• humans have a mutation rate of ~2.5 × 10^-8 mutations per generation → BUT the number of new mutations PER individual may be large

  • Humans have around 160 new mutations per transmission (each of us has 160 unique mutations that other people do not have)

• Mutations are random but common

• Mutation types:

  • single base pair mutations

  • translocations

  • deletions/duplications

  • whole genome duplications

  • inversions

  • transposable elements

  • retrovirus insertions

  • chromosome fission and futsion

• Mutations can either be beneficial, deleterious or neutral —> they can also have small or large effects —> they can also be dominant or recessive

• most mutations are directly selected out of a population

Distribution of fitness effects (DFE)

• this looks like a continuous ditribution

• most effects of mutations are small —> most new mutations reduce fitness ( a little)

• fitness effects of mutations —> less than 1 = deleterious and decrease fitness and fitness greater than 1 are probably beneficial mutations

  

Heterozygosiry = H

• this is the fraction of sites that are heterozygous → more heterozygous genotypes = higher heterozygosity

• humans have a heterozygosity of 0.1 → therefore diversity within humans are low

• higher heterozygosity = lower offspring (ex., hybrids survive but rarely reproduce)

3 reasons for how genetic and phenotypic polymorphism is maintained

→ polymorphism: different phenotypes = different genotypes

1. balancing selection: selection sometimes acts to maintainvariation

2. Mutation selection balance: the rate of mutation and the rate of selection are both similar emough that the mutations are not gotten rid of due to the rate of new mutations being too fast

3. mutation-drift balance ( neutral theory): genetic drift

Balancing seelction

• when selection can maintain balanced polymophism in a population

  1. overdominance or heterzygote advantage: Heterozygotes for an allele have a higher fitness than either homozygote

  2. negative frequency-dependent selection: selction favors rare morphs —> states that it is better to be different → this increases trait diversity

  3. spatially or temporally variable selection: variation in selection across space or time maintains genetic variation

Overdominance and Underdominance

• Best genotype = combination of 2 different types of alleles

• over mean fitness when there is an intermediate frequency of alleles → p is in the middle → this maintains polymorphism for more favorable genotypes → heterozygote is the BEST

  

• Underdominance: when the heterozygote individual is the worst → the AA or aa genotype is the best

• Example: sickle cell anemia → the patient is less susceptable to malaria when they have a heterozygous genotype for those with mild anemia (Ss = mild anemia) → (SS = sickle cell anemia) → thisis because the RBCs have shorter life spans → this gives the plasmodium less time to reproduce

  If a heterozygote has the HIGHEST fitness = heterozygote advantage = overdominance

Negative frequency-dependent selection

• genotype/phenotype has a fitness advantage when it is rare, but its fitness decreases as it becomes more common

• fitness is negatively correlated with frequency → lower frequency = higher fitness

• rarity is an advantage

Spatially and temporally variable selection

• variation in a phenotype of genotype is maintained by variation in selection patterns across environments → one allele has a fitness advantage in one environment while another allele has a fitness advantage in another environment

• e.g. Bird beak shapes → change yearly based on drought → smaller or bigger → adapt to time and environmental conditions

• spatial and temporal selection can occur at the same time

• local adaptation = a form of variable selection

Things that determine the amount of variation in a population

• mutation selection balance

• mutation and inbreeding (gene flow) between populations

Ge

Gene flow

• homogenizes allele frequencies UNLESS selection prevents it → if it does then we get a migration selection balance → how gene flow (migration) and natural selection interact → equilibrium that forms when:

  • Migration brings alleles into a population → continuously introduces new variants to a population

  • Selection works against those alleles

  • two forces balance out so the allele stays at an intermediate frequency instead of being lost or fixed

• If selection eliminates deleterious variants, variation can be maintained

  

Mutation selection balance

• mutations continuously introduces new variants to a population → if selection eliminates the deleterious mutations → variation can be maintained

• mutation = MAIN SOURCE or genetic variation

• stronger selection = rate of taking away deleterious variatns in the population is faster

• Weaker selection = rate of taking away deleterious variants in the population is slower

Mutation selection equilibrium

• Deleterious alleles that dont have a too strong of an effect in the heterozygote can be maintained at low frequenes in the population → recessive deleterious alleles

1. Mutation introduces new variation into a population

2. Random genetic drift determines heather a neutral allele will be fixed or (usually) lost

3. At equilibrium, there is a balance between mutation and genetic drift

Inbreeding depression

• reduces fitness of inbred individuals due to deleterious mutations

• reduced fitness in offspring that results from mating between relatives.

• more recessive mutations should segregate at high frequencies under mutation-selection balance

1. Expression of deleterious recessive alleles

   • Normally, recessive harmful mutations are “hidden” in heterozygotes.

   • Inbreeding makes offspring more homozygous, so these bad alleles get expressed.

   • Example: genetic disorders in royal families with lots of cousin marriages.

2. Loss of heterozygote advantage (overdominance)

   • Some genotypes (heterozygotes) are fitter than either homozygote

   • nbreeding reduces heterozygosity, lowering this benefit

• The closer the parents are to each other (genetically) → the lower of the mean lifespan of children → this is due to everyone having these recessive negative deleterious mutations hiding in our genomes under our dominant alleles

Polymorphism

1. Overdominance 

   1.  Having A2 always better than A1 → directional selection

   2. Overdominance: heterozygous genotype is the most fit → aka heterozygous advantage

   3. Eg. sickle cell anemia → maintains variation of an allele in a population

2.  Mutation - selection balance → reasons we might see variation in a population

   1. “Giant sink of all of our alleles in a population” 

      1. → lots of allele variation = full sink

      2. → little allele variation = empty sink

      3. Need to induce mutations (faucet → fills the sink up)

      4. New alleles → everyone looks more different

      5. Selection: can remove alleles in our population (drain) → “directional selection” that is natural selection

      6. We can get an equilibrium of our variation → called the Mutation Selection Equilibrium

      7. We need to know μ: rate of mutation

      8. s = selection coefficient

      9. h = dominance coefficient

3. q(eq) = mutation rate (μ)/ ((selection rate(s) * dominance coefficient (h)))

4. Balance between mutation → Genetic drift

• we dont believe in selection → we believe in a more random process where we take variance outside of the population

• instead of selection we get drift

• mutation drift equilibrium

  • Ne = (N = number of things we see → E = means effective)

  • Ne = effective population size → if mutations add things to a small population → “size of an idealized population (one that follows Hardy–Weinberg assumptions perfectly) that would experience the same amount of genetic drift, inbreeding, or loss of diversity as the real population”

  • larger population size = more even probability of allele frequency

  • genetic drift → more effective in smaller populations

• neutral alleles are alleles that don’t impacts fitness → synonymous mutations and codons → change in third codon doesn’t change the fitness of an organism

• selection

Neutral theory of molecular evolution

• most mutations are deleterious and are lost immediately

• Most observed molecular polymorphism and genetic substitutions are neutral → consistent with high levels of genetic polymorphism and molecular clock

• Frequency of neutral alleles are controlled by:

  • Mutation rate

  • Genetic rate