Population Genetics

Question 1

Polygenic Inheritance

Answer 1

Many phenotypic differences are said to be due to allelic inconsistencies at a single locus.

However, polygenic inheritance is that which requires the participation of 2 or more genes to produce a phenotype.

IN REALITY there is no trait that only involves a single gene. However, when we look at mutants we are looking at the impact of the mutant allele. Some alleles at the individual loci can make major differences in phenotype.

Question 2

Discrete vs Continuous traits

Answer 2

Discrete - you don’t have to measure the phenotype; it is either there or it isn’t e.g. you are either a dwarf or not.

Quantitative - needs to be measured because it has a frequency distribution (with mean, range, standard deviation etc.) and precise measurement e.g. the heights of dwarves vary slightly and this can be measured.

Question 3

Traits

Answer 3

Same phenotype - many possible causes

Many genes:

Many genes contribute to phenotype and traits such as height rely on additive genes.

Those with more + wild type alleles will have more of the phenotype than those with less. Many traits arise as the product of biochemical pathways, and genes affect each part of the pathway.

One gene plus the variation induced by the environment produces a distribution and each genotype can be stacked to produce a bell curve with a single mode.

Environment:

Phenotypes are often different in different environments. This difference can be due to environment not genotype. Also, a genotype may be superior only in certain conditions which means the environment affects its expression.

Trait = due to genes and environment. What we want to know is how much input each factor has into the trait. You inherit genes from your parents, but you also grow up in a shared environment with them that makes you resemble them just as a much.

Heritability vs. familiality = Heritability arises from shared genotypes, however traits are familial if members of the same family share them, for any reason not just genotypic.

Question 4

Additive Genetic variation

Answer 4

• most valueable for breeding exponentially
• A1A1 = lowest yield
• A1A2 = intermediate yield = mean of A1 and A2, predictive
• A2A2 =highest yield
• can sum across loci, predictive
• can reliably select to change phenotypic distribution

Question 5

Dominance

Answer 5

Dominance unpredictable and not useful for breeding i.e. A1A2 same as A1A1 = A1 dominant

Overdominance = A1A2 higher yield that A1A1, good for breeder but unpredictable

Question 6

Total phenotypic variance

Answer 6

1. easily calculated
2. made up of components

Vphenotypic = Vgenetic + Venviro.

Vphenotypic = Vadditive + Vdominance + Venviro.

Question 7

Heritability

Answer 7

• narrow sense heritability
• h² = Vadditive/Vphenotypic
• proportion of phenotypic variance due to genetic variance
  1. Offspring-parent regression:

h² = 1, max heritability value

h² = 0, no relationship between offspring and parent

h² between 0 and 1

y = mean of offspring

x = mid parent = (mum+dad)/2

2. Response to selection

selection differential = strength of selection = mean_sp - mean_F

Response = mean₀ - mean_F

h² = response/selection differential

h²= (mean₀ - mean_F)/ (mean_sp - mean_F)

Heritablity only valid in environment in which it is measured, can be changed by environment >> cannot extrapolate, specific to the ‘population’ in which it is measured as it depends on available additive variation

Broad sense heritability

= Vgenotypic/Vphenotypic

Question 8

Population Genetics

Answer 8

Population genetics is a direct extension of Mendel’s laws, molecular genetics, and Darwin’s ideas.

Population genetics is the study concerned with measuring levels of variation, examining factors which influence these levels, and thus explain these levels.

The focus is on the population not the individual and only individuals that are reproductive really count since only they contribute to the gene pool.

Population = a group of individuals in the same species that are able to breed with one another. These large populations are usually composed of smaller groups called subpopulations.

Subpopulations are also known as local populations and/or demes and the individuals within them are far more likely to breed with each other than members of the general population. This is often due to geographic or ecological barriers. Populations can change and mathematical theories have been developed to predict how this will change the gene pool:

• size
• geographic location
• genetic composition (allele frequencies)

Question 9

Detecting and measuring variation

Answer 9

- Visible phenotype = although some alleles do affect the visible phenotype there are countless others that do not and thus you can’t detect them with visible phenotypes.

- Chromosomal rearrangements = large chromosomal rearrangements such as inversions can be seen down a microscope.

- Immunological markers = these are phenotypes we can recognise using antibodies. There are over 30 blood groups in humans which is all well and good except we still miss variation because there is allelic variation within these different phenotypes.

- Allozymes = variations in enzymes and proteins can be measured using electrophoresis. However, this only detects variation when the allele changes the amino acids and its charge and the DNA is in the coding region. Two ore more enzymes (encoded by the same gene) with alterations in aa sequence, may alter their mobility during gen electrohphoresis.

• Restriction site variation = cutting out parts of DNA. Limited to where you cut. RFLPs.
• DNA sequencing = the ultimate method that detects ALL variation.

Question 10

Factors involved in DNA sequencing

Answer 10

Single nucleotide polymorphisms - single nucleotide changes in the same location of the genomes of two naturally occurring individuals.

Microsatellite number (tandem repeats) = detecting variation in the amount of microsatellite copies. Very useful for identifying people in disasters, forensics etc.

Variation among homologous DNA sequences = sequences don’t always have to lie entirely within the genes.

Question 11

Haplotype Networks

Answer 11

A haploid genome, the DNA molecule within a single chromosome. These can be compared with one another using haplotype networks.

• look at variation within/outside genes
• look at variation across genes
• see evolution between haplotypes
• how variation within genes evolved

Question 12

Variation present in natural populations

Answer 12

Two parameters:

1. Heterozygosity - under HW law
2. Nucleotide diversity

Heterozygosity = the amount of individuals that are heterozygous for a gene in a population.

Heterozygosity is measured with expected heterozygosity and observed heterozygosity (for single loci).

For multiple loci = average heterozygosity

Gene diversity = expected heterozygosity.

H_exp = 2pq = 1-(p² + q²)

Gene diversity can be calculated for a single nucleotide site (H_exp for that nucleotide)

Nucleotide diversity is the average gene diversity across all nucleotide sites in a gene including the ones that vary and the ones that don’t.

Question 13

Gene pool

Answer 13

• individuals that contribute to gene pool of next generation

Question 14

Allele

Answer 14

• only 2 gene sequence that differ at all in any nucleotide, classified based on phenotypic differences
• if we recognise based on phenotype, many different sequences for that gene may yield the same phenotype

Question 15

Vertebrates

Answer 15

• low variation
• more variation in invertebrates and unicellular organism
• age of species relate to amount of variation
• small subset of variation is significant to phenotype (5 million nucleotide differences between individuals)
• common SNPs every 300 to 1000 bp in human genome
• common = if the less frequent variant occurs at a frequency of 5% or greater

Question 16

Polymorphism

Answer 16

Aside: There are two meanings of allele kind of - there is that in which we refer to sequences being alleles if they have any nucleotide difference. However, we can also define alleles as sequences that result in a different phenotype not necessarily just a different code.

Polymorphism:

Refers to when there are two or more alleles at a locus and the rarer allele has a frequency in the population higher than can be explained by mutation alone. Most genetic disorders in humans occur at frequencies too low to be considered polymorphisms.

Balanced (stable) polymorphism = allele and genotypic frequencies are maintained by balancing selection.

• mechanisms:
  1. environmental heterogeneity
  2. heterozygous advantage (hetero. has highest fitness)
  3. frequent dependent selection - the rare the genotype, the fitter

Transient polymorphisms = when allele and genotypic frequencies are changing and variation is decreasing due to genetic drift. Process may be very slow.

Question 17

HW Assumptions

Answer 17

1. • Random mating
2. • Infinite population size
3. • No selection
4. • No migration
5. • No mutation

• most populations conform to HW
• small net effect of non-assumptions i.e. non-random mating

Degrees of freedom for chi-squared = no. of phenotypes - no. of alleles.

Question 18

Consequences

Answer 18

When alleles are rare, they essentially never exist as homozygotes in a population. However, Heterozygotes aren’t uncommon and if these were homozygous it would be lethal or result in a debilitating disease.

Sex linked conditions are more common in males because the frequency is p vs. p^2 for females and if the allele frequency is small this is significant.

The ratio of males: females with colour blindness is 12.5:1. wow

Question 19

Mutations

Answer 19

Mutation is the source of all genetic variation. We have 1 billion base pairs in our DNA and amazingly very few errors occur and those that do are corrected immediately.

However, if this damage is not repaired then a mutation results. This can happen in:

• Germ line = somewhere in the production line of the gametes a mutation occurs and thus this is transferred to the offspring. These cells are haploid. Mutation lost if that germline not fertilised.
• Somatic mutation = mutations that occur in the somatic cell division of an adult resulting in a changed phenotype in that cell line. This can cause genetic mosaics and is not passed onto the offspring.

Case study: Cancer = cancer is always genetic (results from crazzzy cell division) however it is not always transferred genetically. It can arise in the germ line or the somatic cell.

u = mutation rate

N = number of individuals produced in a generation

N = diploid inviduals produced with 2N gametes

2Nu = new mutations per generation at a locus

Question 20

Fate of new mutations

Answer 20

Mutations are extremely rare and cannot solely explain high frequencies of alleles. However, populations and genomes are very large so it’s not surprising that we do observe some new mutations.

If new mutations make it past the obstacles and into the population, they face more hurdles:

• natural selection acts to remove most mutations because they’re usually not beneficial
• most new alleles are lost by chance, genetic drift despite selection.
• some alleles do survive to contribute to polymorphism however this is due to other factors not mutation alone.

BUT recurrent mutations cannot make an allele polymorphic

whilst mutation is the sole cause of variation it does very little alone in terms of changing allele frequencies over time.

Question 21

Unidirectional Mutation

Answer 21

Mutation that occurs in one direction: A1→A2 at the rate of u.

p_o = the initial frequency of A1
p_t = the frequency of A1 after t generations

u = mutation rate

p_t = p_o(1-u)^t

Assumptions:

• infinite population size
• there’s no selection
• mutations are recurrent, at a constant rate, and not reversible (no back mutation).

Question 22

Forward and back mutation

Answer 22

When both forward and backward mutations can occur. A1←→A2

p = the frequency of the A1 allele

q = the frequency of the A2 allele

u = frequency of p→q mutation

v = frequency of q→p mutation

The frequency change over generations is shown by:

Δp=p₁ -p_o =vq_o -up_{<strong>o</strong>}
The rate of this change is shown by a fancy formula shown on the formula sheet.

allele frequencies change very slowly through mutation and forward and back mutation can often be mistaken for unidirectional mutation.

if allele freq. >1%, mutation is not the only contributing factor

Question 23

Genetic drift

Answer 23

Random, non-directional

Genetic drift is the changing of allele frequencies through random sampling error that occurs through the sampling of alleles from sperm and eggs.

The sampling error is inversely proportional to the amount of samples taken (gametes in the population reproducing). Thus genetic drift is weakest in larger populations.

Genetic drift often results in the fixation of alleles where an allele is eradicated so no more change can occur. Time of fixation related to population size.

Allele frequencies float aimlessly due to the sampling error of genetic drift. When they bounce around aimlessly for long enough they hit a wall and become fixated. It’s not a force, it’s just random and it occurs in all finite populations in combination with the other hardy Weinberg factors.

Pronounced in:

• small population
• founder events
• bottlenecks

Question 24

Effective Population Size

Answer 24

the number of reproductive individuals in a population. Represented by Ne.

You must take into account the respective numbers of males and females when calculating effective population size (depends on which gender is in excess). We do this with the formula:

Ne = 4NfNm/Nf + Nm

if Nf=Nm, Ne = Nf+Nm

Question 25

Bottleneck

Answer 25

when a population is reduced dramatically in size by a disaster, seasonal change etc.

This randomly eliminates individuals, regardless of genotype causing a drastic change in allele frequency.

period of bottleneck may be influenced by genetic drift

Question 26

Consequences of genetic drift

Answer 26

• Small populations have larger deviations from parents
• Genetic drift always accumulates to lead to fixation of one allele - ALWAYS
• The time to fixation depends on the effective population size.
• The probability that an allele will become fixed is equal to its frequency.
• mean allele freq. will not change
• heterozygosity decreases in all populations
• different alleles fixed in different populations (genetic differentiation)

Question 27

Genetic Drift - Maths

Answer 27

Predicting the range of allele frequencies after one generation = we first calculate the standard deviation by finding the variance and square rooting it.

Variance = pq/2N (use Ne – effective population size - instead if it’s available)

Using the empirical rule this means that 95% of populations will have an allele frequency within two standard deviations of the mean.

This gives us the range and corroborates the idea that sampling variation decreases with population size increase.

The fate of new mutations with regard to genetic drift:

The number of mutations that arise is 2Nu as we know.

The probability of any given becoming fixed is 1/2N (probability of elimination is 1-1/2N). The number of mutations fixed per generation per locus is:

2Nu * 1/2N which equals u.

Time to fixation: given by t = 4N where t is the average number of generation to achieve fixation and N is the number of individuals in the population assuming males and females contribute equally.

Question 28

2 levels of sampling error when small population moves out of a big population

Answer 28

• the founder effect where the sample taken out is not a true representation of the larger gene pool
• the increasing in sampling error that occurs over time because the new population is so small in number.

Question 29

Founder Effect

Answer 29

The Amish population of 12,000 in Pennsylvania is derived from about 400 settlers that came from Europe. This is a great example of the founder effect where a few individuals give rise to a large population and contribute much more to the gene pool than in regular populations.

• not all founders contributed equally
• inbreeding common

Question 30

Natural Selection

Answer 30

The opposite of genetic drift for it is most definitely NOT random. Changes average allele frequency.

Evolutionary theory was proposed almost simultaneously by Darwin and Wallace.

Darwin’s propositions:

• A population includes individuals that have varying phenotype
• Some of these phenotypes will be more successful at surviving and reproducing
• These phenotypes will increase in frequency as long as their selective advantage is maintained.

A modern proposition:

• Within a population there is genetic variation that arises from differing DNA sequences. Some of these differences encode different proteins that have different function.
• Some alleles code for proteins that enhance an individual’s survival or reproductive capacity.
• Individuals with these alleles are more likely to survive and reproduce
• Thus over the course of many generations allele frequencies will change through natural selection. This will significantly alter the characteristics of species and the net result is a population that is better adapted to its environment.

Advantages:

• *Promotes adaption** - selective agents cause adaptations
• *Buffers the species** - protects the species against the randomising influence of migration, mutation, and genetic drift.

Explains diversity - promotes the adaptation of different phenotypes depending on what environment they’re in.

Question 31

Relative Fitness

Answer 31

The capacity to survive and reproduce. It has these components:

• Mating success = how successful is one genotype at mating
• Fertility = how many gametes are produced and how well they work
• Fecundity = the capacity to fertilise eggs
• Viability = the percentage of fertilised eggs that complete development time
• Development time = the speed of development
• Longevity = often not important for fitness.

Selective agents - physical or biological factors in the environment that cause certain phenotypes or genotypes to have advantages. Directional. Discriminates between phenotype/genotype.

Question 32

Algebra

Answer 32

w = the relative fitness value

s = selection coefficient

w=1-s
s=1-w
0<w></w>0

everything scales to 1

Question 33

Estimating fitness

Answer 33

2 methods:

1. using components of fitness
2. departure from mendelian expectations in lab crosses
   - assume all genotype equally fit e.g. 1:2:1 ratio expected

Question 34

General Selection Model

Answer 34

1. large pop. size
2. random mating
3. no new alleles introduced by mutation
4. no migration
5. 2 alleles at 1 locus
6. relative fitness values constant
7. fitness effects due to genes at other loci impact upon all 3 genotypes equally

Question 35

Directional Selection

Answer 35

• Where one of the homozygotes has a relative fitness of 1 and in order to maximise fitness selection will increase the frequency of the genotype.
• Equilibrium occurs when allele becomes fixed and variation is lost.
• This selection leaves a distinct signature because the favoured genotype carries some of the surrounding alleles with it (selective sweep)

directional selection = q^hat = 1

balancing selection = q^hat = between 0 and 1

Question 36

Migration or independent origin

Answer 36

• look at chromosomes and associated mutations e.g. SNPs, same pheno but different geno?
• same SNP = migration
• different SNP = independent origin
• more associated SNP suggests more recent origin (less time for recom.)

Question 37

Selection and mutation

Answer 37

• for deleterious alleles, selection and mutation oppose each other
• at low equil. allele freq. maintained

“water in (mutation), water drained out (selection)”

• natural selection eliminates homozygotes (recessive lethal, w=0), reduces chance of child bearing for hetero (w=0.2)
  e. g. Dwarfism

4/5 dwarves have unaffected parents

new mutation = u = 1/20,000 gametes, if new mutation is the only reason, there’d be many different alleles

Question 38

Medical Intervention

Answer 38

• influence alllele frequency
• medicine increases the fitness and equil. freq.
• prenatal testing and abortion decreases fitness and equilibrium freq.

Question 39

Four classes of variation based on freq. and persistence

Answer 39

1. variation lost soon after it arises (freq. extremely low)
2. variation held at low freq. by mutation-selection balance (freq. proportional to u/s)
3. transient polymorphism (genetic drift)
4. balancing polymorphism (balancing selection)

Question 40

Environmental Heterogeneity

Answer 40

• selective agents are always some component of the environment
• affect reproductive output and relative fitness
• selection pressures and relative fitness vary
• enviro. heterogeneity for a selective agent means that relative fitness values vary
• enviro. heterogeneity can maintain variation in pop., can also mean different pop. have different allele freq.
  1. climatic factors: temp., rainfall, humidity
  2. substrate: food/nutrition, host plant, host animal, soil type, water, toxins
  3. Biotic factors: parasites, competitors, preditors
  4. time (temporal)
  5. space (spatially/geographically)

Thus:

• selection coefficient vary temporally/spatially therefore, allele freq. will vary temporally/spatially
• allele freq. will be correlated with variation in selective agent (environmental factor)

Question 41

Selection Mechanism

Answer 41

• how selection via environment works at the molecular level? Environmental heterogeneity
• e.g. Dieldrin resistance
  1. Genetic variation must be shown to exist
  2. Allele frequencies must be described over time in one population or through space across populations
  3. Demonstrate phenotypic diversity among genotypes for an aspect of molecular function
  4. Knowing
• Function of the gene product
• Nature of the functional differences between the products of the alleles
• The ecology of the organism

Postulate a relevant, discriminatory selective agent

5. Differences in molecular function must be reflected in fitness differences in postulated selective regime
6. Natural populations must be re-examined to seek a comprehensive explanation for observed allele frequency distributions in space and time

Question 42

Heterozygous Advantage

Answer 42

• hetero advantage, candidate for explanation for many of polymorphisms observed in pop. of all organisms
• hetero ad. and freq. dependent selection maintain variation in pop.

Question 43

All genotypes equally fit?

Answer 43

• selective neutrality
• variation at DNA level does not impact gene function at all or to a degree that selection discriminates
• variation will be subject to genetic drift
• polymorphism will be transient - lost at a rate that is dependent on Ne
• variation in some regions of genome more likely to be selectively neutral
• variation may be selectively neutral in some enviro. and not in others

Question 44

Non-random mating

Answer 44

Assortive mating:

• individual of geno. mate more/less frequently with individual of given geno. than expected from their respective freq.

Question 45

Inbreeding

Answer 45

• higher freq. of mating between relatives than expected for randomness
• inbreeding coefficient = F = probability that an individual receives, at a given locus, 2 alleles that are identical by decent (comes from one individual earlier in family tree)
• F values in notebook
• F high in isolated populations e.g. religious communities - Dunkers

Question 46

Properties of inbreeding

Answer 46

• allele freq. DO NOT change BUT genotype freq. changes
• increase homozygosity
• decrease heterozygosity
• lose heterozygosity in proportion to F, gain homozygosity in proportion to loss of heterozygosity
• consistent inbreeding leads to cumulative increase in F
• often occur in small populations
• may occur in parallel with genetic drift e.g. Amish
• inbreeding homozygotes rare deleterious recessive alleles producing reduction in fitness - reproducing with relateive increases chance of deleterious allele meeting

Question 47

Gene flow and migration

Answer 47

• exchange of genes between 2 populations (uni/bidirectional) following migraton (individuals that reproduce)
• source pop. = freq. of A1 = P (constant)
• recipient pop. = freq. of A1 = p^bar
• gene flow = m
• gene freq. will change until:

pt^bar = P

m = 0