BIO260 Final

What is population genetics?

Study of genetic variation within individuals and populations

What are some examples of population characteristics?

Population structure
Breeding system
Demography

What are the evolutionary forces studied in class?

Mutation
Migration
Natural Selection
Genetic Drift
Recombination

What are SNVs?

Stands for single nucleotide variant
Varies at a single nucleotide

What are SNPs?

Single Nucleotide polymorphism
Single nucleotide variants that exist at a certain % in the population

What is a Synonymous mutation?

AKA a silent mutation
A mutation that does not change the amino acid sequence

What is a non synonymous mutation?

AKA missense mutation
A mutation that changes the amino acid sequence

What is a nonsense mutation?

A mutation that results in a premature stop codon
Eg. mutation changes a regular codon to a stop codon

What is a frameshift mutation?

A deletion that results in a premature stop codon
Base is gone, changes “unit” being read

What is a Locus?

A specific area in the genome

What is monomorphic loci

A locus with no variation

What is polymorphic loci

A locus with multiple variants

What is an allele

Different forms of the same locus

What is a major allele

The allele at the highest frequency

What is a minor allele?

A low frequency allele

What is polymorphism?

Co-occurrence of 2 or more alleles at a locus within a population

What is heterozygosity?

FRACTION OF INDIVIDUALS in a population expected to be heterozygous at a particular locus GIVEN THE ALLELE FREQUENCIES at that locus
A POPULATION STATISTIC, not statement of genotype

How can a locus be polymorphic, have no heterozygous individuals, and still have heterozygosity?

Heterozygosity is just a population statistic, not a statement of genotype, so all the polymorphic individuals might be homozygous for the trait, but they’re in the population, so it makes the population as a whole heterozygous

What is the maximum heterozygosity for two alleles in a population?

0.5

What happens to heterozygosity when you improve the balance between alleles in a population?

The heterozygosity increases

What happens to heterozygosity if you increase the number of alleles and balance their frequencies?

Heterozygosity approaches 1

What happens to diversity every time humans migrate?

Decrease in diversity due to bottlenecks

What is observed in terms of population diversity where humans first originated?

Larger population diversity

What happens to heterozygosity when you reduce population size?

The heterozygosity decreases

What is effective heterozygosity?

The probability of sampling two different alleles from a haploid population
Basically the number of times we would go into population and expect to find heterozygotes

What is the difference between heterozygosity and effective heterozygosity?

Heterozygosity is not an individual measure, and is more about the population and its diversity as a whole
Effective heterozygosity, on the other hand, is more about how many individuals in the population are heterozygotes

What are the assumptions needed for hardy weinberg?

Random mating population
Infinite population size
No mutation
No selection
No migration
Some assumptions about our specific genetic model (eg. diploid, 2 alleles)

What does it tell us if something other that mendelian genetics is going on (ie. if we cannot fulfill hardy Weinberg assumptions)?

There’s evolution happening

Describe a population in hardy weinberg equilibrium

Null hypothesis
Has not violated any of our assumptions
Therefore, genetic diversity at that locus is not being strongly or immediately influences by the forces of evolution

Describe a population not in hardy weinberg equilibrium

Alternative hypothesis
Violates our assumptions
Therefore, genetic diversity at that locus is being strongly or immediately influences by the forces of evolution

What formula do we use to calculate allele frequencies in hardy weinberg equilibrium?

p+q\=1

What formula do we use to calculate genotype frequencies in hardy Weinberg equilibrium?

p^2+2pq+q^2\=1

Why don’t we calculate heterozygosity as 2pq?

Because our other formula for heterozygosity can be used with multiple alleles at multiple loci and is less complicated

What are the implications of the Hardy Weinberg equilibrium?

Can be observed after just one generation irrespective of genotype frequencies if HWE assumptions are upheld
Genotype frequencies in successive generations are determined only by random mating and by the properties of probability (Mendel’s laws)
No change in genotypic frequencies over time, and therefore no loss of genetic variation over time

Why do we use Hardy Weinberg, if there are so many assumptions? Are they ever true?

Yes, because they only apply to the specific locus under study
So if you’re looking at a “neutral” locus (eg. silent substitution), you might find it under HWE

What is population structure?

Spacial Structure or organization of genetic variation

Differences in allele frequencies  between different populations of a species

Eg. humans show major differences where few genetic differences exist (very little structure in human population)

Butterflies have few perceived differences where major genetic differences exist

SAME GENES, DIFFERENT ALLELES

Unrecognized population structure can cause a \_____ in heterozygosity

Reduction

What are the three levels of genetic structure?

I (individual)
S (subpopulation)
T (Total population)

What are Heterozygosity indices?

Heterozygosity calcul;ated at different levels of the population structure

What is HI?

The observed heterozygosity for an individual in a randomly mating global population

What is HT?

The expected heterozygosity for an individual in an randomly mating global population

What is HS?

The expected heterozygosity for an individual in a randomly mating subpopulation, averaged over subpopulations

How do we calculate Average Expected Heterozygosity (HS)?

We add up all of the expected heterozygote frequencies from all of the subpopulations, and then divide by the number of subpopulations

What is F statistics?

Fixation Indices
Developed to study inbreeding (homozygosity)

What is FIT?

Total homozygosity (homozygosity \= 1-heterozygosity)
Mean deficiency of observed heterozygotes among individuals with respect to that expected for the total population
(individuals vs total)

What is FIS?

Inbreeding coefficient (probability of identity by descent)
Mean deficiency of observed heterozygotes among individuals with respect to that expected expected across subpopulations
Observed correlation of uniting gametes relative to gametes drawn at random from within a subpopulation
Expected percentage of homozygosity arising from a given system of breeding

What is FST?

Population substructure
Primary statistic used to quantify population differentiation or structure (tells us if we actually have it in our population)
Mean deficiency of expected heterozygotes among subpopulations with respect to that expected for the total population
Observed correlation of gametes within subpopulations relative to gametes drawn at random from the entire population
Proportion of the total genetic variance contained in a subpopulation relative to the total genetic variance

What is mutation?

Any (non repaired) alteration in the nucleic acid sequence of an organism’s genome
The ultimate source of all genetic variability \>>> how variants arise; occur at “clocklike” rate (steady rate over time)

What allows us to use mutations to put a timescale on evolution?

The fact that they occur at a steady rate over time (even though there is a very high variance)
Therefore, the number of mutations that have accumulated is proportional to the time that they have been accumulating

What is genetic drift?

Change in allele frequencies due to random sampling variation between generations
Stochastic sampling process
Relaxation of infinite population sizes (only significant in finite populations, magnitude is inversely and entirely related to population size)

The larger the population, the (more/less) often than not that there remains variability

More

Smaller populations end up fixed (more/less) often

More

Why do we care about genetic drift?

The stochastic changes in allele frequencies occur without respect to the fitness of the individuals or alleles, and there's no way to predict the outcome based on starting conditions
It decreases heterozygosity and increases homozygosity by chance, therefore increasing likelihood of exposing deleterious recessive alleles (which are more likely to rise up in smaller populations)

What is identity by descent?

A locus in two or more individuals that have been inherited from a common ancestor without recombination

Genetic drift is dependent on \_____

Population size

What are the two measures of population size?

Census population size(N) and effective population size(Ne)

What is census population size?

N
The number of individuals in a population

What is effective population size?

Ne
“Genetic size” of the population
Number of individuals in an ideal population that would lose heterozygosity at the same rate as the actual population
Reflects the decrease in a population’s heterozygosity due to violations of HW assumptions

What is π?

nucleotide diversity
A measure of heterozygosity
Number of nucleotide differences per site between two DNA sequences in all possible pairs in the sample population

What is μ?

A measure of heterozygosity
The mutation rate per nucleotide per generation in a population

What happens to the effective population size as the pairwise nucleotide diversity increases?

The effective population size also increases (lecture 3 slide 49)

What are some ways genetic drift reduces heterozygosity?

Inbreeding
Assortative (non random) mating)
Breeding systems
Unequal sex ratios
Unequal number of offspring
Fluctuations in population size
Population bottlenecks and founder effects

What is inbreeding?

Mating between relatives
Increases probability of identity by descent (IBD)

What does inbreeding result in in terms of homozygosity/heterozygosity?

Builds up homozygosity, loses heterozygosity

More distance between mates means (more/less) time to lose heterozygosity

More

How homozygous was Charles II of Spain?

~25% of his genome
More homozygous than that of a child whose parents were siblings

What is assortative (non random) mating?

Mate choice influenced by shared trait(s), not random chance
Can be either positive (more frequent) or negative (less frequent) than experienced by chance

What are some examples of positive assortative mating in humans?

Age
Ethnicity
Religion
Height and weight
Education
Socioeconomic status
“Disability”
Facial appearance

What are some examples of negative assortative mating in humans?

HLA and scent
Red hair

Describe why Genghis Khan is a good example of a drift event

1 person had lots of offspring

Describe the link between huntington’s disease and genetic drift

Very prevalent in Barranquitas, Venezuela
History traced back to a single woman who carried the Huntington’s allele and had lots of kids, therefore passing trait on
First instance of genetic trait being mapped

Ne is estimated by the \_____ of the actual population, and is sensitive to \____ numbers

Harmonic mean; small

What is natural selection?

Differential reproductive success of genotypes
Deterministic force that promotes adaptation
Can predict the outcome given knowledge of the starting conditions and parameters of the process, as opposed to genetic drift, which is a stochastic force that gives unpredictable outcomes
Dependant on fitness differences between genotypes

Describe fitness (darwinian)?

Relative reproductive success of a genotype
Probability of survival and rate or reproduction of an average individual of a specified genotype

What is environment dependant fitness?

Same genotype will have different fitness in different environments

What is relative fitness?

Fitness of one genotype relative to a reference genotype

What is directional selection?

Selection acting on a single allele
Most prevalent type of selection
Often decreases genetic diversity

What are the two types of directional selection?

Positive selection (increase)
Negative (purifying) selection (reduce prevalence of allele)

What is balancing selection?

Selection acting to maintain multiple alleles in a population
Maintains genetic diversity (because you’re acting on multiple alleles)

What are the types of balancing selection

Heterozygote advantage
Heterozygote disadvantage
Negative frequency dependant selection

What is positive selection

Selection for a beneficial allele

What is negative selection

Selection against a detrimental allele

What is MSC

Minimal selective concentration
The fitness cost of resistance equals antibiotic conferred selection for the resistant mutant
The abiotic concentration where only the susceptible strain starts to suffer/die off but resistant strain continues to vibe

What is MIC

Minimal inhibitory concentration
Lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism
Basically where the strain dies off (different MICs for susceptible and resistant strains)

Why is natural selection so ineffective at removing deleterious recessive alleles(eg. Allele a) from populations?

The rate at which allele a decreases is correlated with its frequency
As the allele a becomes rare, it spends more time in the heterozygous state
Selection can only act on a recessive allele when homozygous
Therefore, recessive alleles are “protected” when heterozygous
Can never get rid of a alleles unless you had a way of detecting heterozygotes

What is stable polymorphism?

A stable equilibrium between alleles
Both alleles are being maintained in population

What is the relationship between positive selection and non synonymous mutations?

In positive selection, there is an excess of non synonymous mutations relative to synonymous substitutions
Implies that these extra non synonymous mutations are beneficial
Beneficial non synonymous mutations rise in frequency due to positive selection

What is the relationship between negative selection and non synonymous mutations?

In negative selection, there is an deficit of non synonymous mutations relative to synonymous substitutions

Implies that these missing non synonymous  mutations are detrimental

detrimental non synonymous mutations removed due to negative selection

In an infinite population the probability of fixation of a new allele is (greater than/less than/equal to_ the selection coefficient on that allele

Equal to

\______ alleles have effectively no chance of being fixed in a large population

Deleterious

Deleterious alleles (do have/do not have) a chance of fixation in a small population

Do have (bc of genetic drift)

What is phylogenetics?

The study of evolutionary history and relationships between organisms

Conversion of comparative data (ie. data collected from multiple organisms) into a tree like branching diagram that indicates the relationship among organisms and the patterns of evolutionary descent

Can be built with many types of data, but we are focused on molecular phylogenies built from nucleotide or protein sequences

What is a clade?

A nested section of a phylogenetic tree
Consists of a node and all its descendants

Describe a cladogram

Just shows branching clade structure
Branch lengths do not represent evolutionary distance or time
Depicts similarity and patterns of relatedness between groups of organisms

Describe a phylogram

Shows branching order AND amount of evolutionary divergence
Branch lengths represent evolutionary divergence and are proportional to time
Depicts evolutionary relationships among organisms or sequences and the amount of change that has occurred over time (different constraints, possibly different mutation rate, but unlikely)

Did humans evolve from monkeys or apes?

Neither!
We share a COMMON ANCESTOR with monkeys, and we ARE apes!

Describe the classical school of population genetics

Polymorphisms are rare and transient
Natural selection primarily removes deleterious alleles via purifying selection (most important form)
Promotes homozygosity
Little genetic diversity

Describe the balanced school of population genetics

Polymorphisms are common and long lived
Natural selection primarily maintains polymorphisms via balancing selection
Promotes heterozygosity
Thought populations had lots of genetic diversity

What did we know pre 1960s about genetics?

Knew about DNA, but did not know structure/how to work with it, therefore had to use phenotypes

What marked the mid 1960s as special?

First molecular techniques
Protein variants \= allozymes
Protein electrophoresis studies of enzyme polymorphisms
Allozyme electrophoresis studies consistently showed very large amounts of variation