Evolutionary Genetics Flashcards by Zaid Shadid

What is time to fixation dependent on?

Population size

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Define

Genetic load

the presence of unfavourable genetic material in the genes of a population

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What is the minimum population size at which an allele with a fitness effect of s = 0.0001 can be acted upon by natural selection

10000

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True or False:

Neutral alleles must eventually become fixed or lost

True

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What are the important factors when figuring out how long it will take for a beneficial mutation to fix?

Selection coefficient and current frequency in the population

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Define

Pseudogenes

segments of DNA that are related to real genes. They have lost at least some functionality, relative to the complete gene, in cellular gene expression or protein-coding ability

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Define

Parallel evolution

the similar development of a trait in distinct species which are not not closely related, but share a similar original trait in response to similar evolutionary pressure

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Definition

a measure of differences in relative fitness. They are central to the quantitative description of evolution, since fitness differences determine the change in genotype frequencies attributable to selection

Selection co-efficient

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Define

Molecular clock

figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleotide sequences for DNA or amino acid sequences for proteins

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How does genome sequence conservation prove that most of the human genome is not functional?

Functionally important DNA sequences are preserved by natural selection. Analysis of 29 Eutherian mammal genomes showed that genome sequences were conserved across only ~4.2% of the human genome

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Definition

the expected number of mutations to occur in each new offspring

Genomic mutation rate

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Define

Selection co-efficient

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What is a 2-fold synonymous site?

A synonynous site (the third site of a codon - GAA) where 2/4 possible substitutions at the third site are synonymous

GAA - Glutamate

GAG - Glutamate

GAU - Aspartate

GAC - Aspartate

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Definition

the process whereby organisms better adapted to their environment tend to survive and produce more offspring. The theory of its action was first fully expounded by Charles Darwin, and it is now regarded as be the main process that brings about evolution

Natural selection

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Definition

the similar development of a trait in distinct species which are not not closely related, but share a similar original trait in response to similar evolutionary pressure

Parallel evolution

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How do new genes evolve?

Errors during recombination and DNA repair can lead to genes (i.e. gene A) being duplicated resulting in two copies of that gene (i.e. gene A1 and A2). The duplicated gene can be lost via mutational degradation, retained by natural selection, or develop an entirely new function

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How do you work out the chance of a mutation going to fixation?

1/2N

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Which population size does genetic drift have a greater effect: 18 or 1800?

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Define

Wright-Fisher model

a discrete-time Markov chain that describes the evolution of the count of one of two alleles segregating at a locus over time

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How can genetic screening stop the spread of deleterious alleles?

Preimplantation genetic screening allows the selective removal of embryo’s that contain disease alleles that have already been identified in the parent and cause disease

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What are the assumptions of the Wright-Fisher model?

Haploid
Constant population size
No mating
Discrete generations (no overlap)
Genes are transmitted to the next generation by sampling with replacement
No selection or mutation

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True or False:

There is no recombination between cancer cell lineages

True

Cance is a somatic disease

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An allele has 100% lethality. What is the predicted equilibrium frequency (f_a) of this allele in the population?

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What is the probability of fixation of a neutral allele?

It’s current frequency in the population

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If N = 100, 1/N = 0.01 Therefore all alleles with a selective effect less than _____ will be seen as neutral by natural selection

0.01

# Definition a discrete-time Markov chain that describes the evolution of the count of one of two alleles segregating at a locus over time

Wright-Fisher model

# Definition variation in the relative frequency of different genotypes in a small population, owing to the chance disappearance of particular genes as individuals die or do not reproduce

Genetic drift

An allele has a selection coefficient of s = 0.04. Approximately how many more generations will this allele take to fix than another allele that has a fitness effect of s = 0.08?

Double

# Definition figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleotide sequences for DNA or amino acid sequences for proteins

Molecular clock

# Define Divergence

the process in which two or more populations of an ancestral species accumulate independent genetic changes (mutations) through time, often after the populations have become reproductively isolated for some period of time

What are the mutations that drive cancer evolution called?

Driver mutations

# Definition a mutation that increases an organism's ability to survive

Beneficial mutations

# Define Fixation

the change in a gene pool from a situation where there exists at least two variants of a particular gene (allele) in a given population to a situation where only one of the alleles remains

# Definition a type of hypoxia-inducible factor in humans, a group of transcription factors involved in body response to oxygen levels

EPAS1

What is the only directional force on evolution?

Natural selection

True or False: The capacity for selection to discern between the fitness effects of alleles do not depend on population size

False It does

# Definition the change in a gene pool from a situation where there exists at least two variants of a particular gene (allele) in a given population to a situation where only one of the alleles remains

Fixation

A screening procedure can eliminate 20% of all the deleterious allele (with a 1% fitness effect) in the population. How does genetic screening change the equilibrium frequency of the disease?

s_d = -0.01 s_screen = -0.21 Results in a 21 fold reduction

How is the selection coefficient (s) calculated?

The starting frequency of a variant, and how its frequency changes over time

# Definition a chromosomal segment that can undergo transposition, especially a segment of bacterial DNA that can be translocated as a whole between chromosomal, phage, and plasmid DNA in the absence of a complementary sequence in the host DNA

Transposon

Label this diagram

An allele has a much higher frequency than expected (lethal in males but rarely lethal in females), why could this be?

X-linkage

# Definition the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified

Synonymous substitution

# Definition the presence of unfavourable genetic material in the genes of a population

Genetic load

# Define Eugenics

the science of improving a population by controlled breeding to increase the occurrence of desirable heritable characteristics

True or False: Probability of fixation of a neutral allele is dependent on population size

False It is independent of population size

What other factors can contribute to genetic load?

Older fathers produce offspring with more *de novo* mutations

What does preimplantation genetic screening miss?

How do you use a molecular clock?

1. Get DNA sequences of the species that you want to compare 2. Count the number of differences between the two DNA sequences 3. Find a way to calibrate the number of mutations with time

# Definition segments of DNA that are related to real genes. They have lost at least some functionality, relative to the complete gene, in cellular gene expression or protein-coding ability

Pseudogenes

What is the expected number of mutations that we expect to fix every generation?

1/2N x 2NU = U (mutation rate)

How long will a mutation take to fix if it has 2s compared to s?

Half the time

Why do *E. coli* have a much smaller genomic mutation rate than humans?

They have a much smaller genome

# Define Genetic screening

the study of a person's DNA in order to identify genetic differences or susceptibility to particular diseases or abnormalities

We know that: * ~20% (10-40%) of mutations in functional regions are deleterious * We can only handle a deleterious mutation rate of ~1 (0.8-1.5) per genome * We have 100 mutations occurring in every individual Why does this prove that far less than 80% of the genome is functional?

16 of the 100 (0.2x 80) mutations would be deleterious. That is far more than the acceptable deleterious mutation rate of 1

# Definition Describes the fact that different organisms having the same general level of biochemical, organic, and morphological complexity and even organisms belonging to the same genus, nevertheless often have widely different C-values - the amount of nuclear DNA in the unreplicated gametic nucleus, irrespective of the ploidy level of the species

Genome size (C-value) paradox

We know that: * ~20% (10-40%) of mutations in functional regions are deleterious * We can only handle a deleterious mutation rate of ~1 (0.8-1.5) per genome * We have 100 mutations occurring in every individual In reality, what proportion of the human genome encodes functional DNA?

How does the C-value paradox prove that most of the human genome is not functional?

Eukaryotic genome size fails to correlate well with apparent complexity (i.e. single-celled amoeba have some of the largest genomes; 100x larger than humans)

# Definition the conservation of functionally important DNA sequences by natural selection

Genome sequence conservation

# Definition an equilibrium in the number of deleterious alleles in a population that occurs when the rate at which deleterious alleles are created by mutation equals the rate at which deleterious alleles are eliminated by selection

Mutation-selection balance

# Define Junk DNA

DNA that does not code for a protein, usually occurs in repetitive sequences of nucleotides, and does not seem to serve any useful purpose

What is the predicted frequency of the blue and orange alleles in the next generation?

# Define Beneficial mutations

a mutation that increases an organism's ability to survive

# Define Natural selection

# Define Neofunctionalization

an adaptive mutation process; meaning one of the gene copies must mutate to develop a function that was not present in the ancestral gene

# Definition a neutral mutation process in which each paralog retains a subset of its original ancestral function

Subfunctionalization

# Define Genomic mutation rate

the expected number of mutations to occur in each new offspring

How does cancer evolve?

1. Initially, the growth of cells is repressed. A driver mutation occurs in one cell that allows escape from the growth repressors 2. Secondary mutations occur, a few will drive further adaptation (increase growth rate or capacity to spread) 3. If chemotherapy is applied to the cancer, the population size is drastically reduced 4. Finally, one cell likely gains a mutation that confers resistance to the drug used for chemotherapy allowing the population size to increase

# Definition an adaptive mutation process; meaning one of the gene copies must mutate to develop a function that was not present in the ancestral gene

Neofunctionalization

# Definition The conversion of a gene into a pseudogene

Pseudogenization

# Definition DNA that does not code for a protein, usually occurs in repetitive sequences of nucleotides, and does not seem to serve any useful purpose

Junk DNA

# Definition the study of a person's DNA in order to identify genetic differences or susceptibility to particular diseases or abnormalities

Genetic screening

# Define Synonymous substitution

the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified

# Define Deleterious mutation

a mutation that decreases the fitness of the organism

What is junk DNA mainly comprised of?

Transposons Pseudogenes

The equilibrium frequency (f_a) of a deleterious mutation in a population depends on what?

The mutation rate to the deleterious allele (μ) f_a = \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ The selection coefficient of the deleterious allele (s)

# Definition a mutation that decreases the fitness of the organism

Deleterious mutation

If 7% divergence between macaques and humans accumulated over 25 million years and Chimpanzee were diverged from humans by 1.2% at neutral sites. Use the molecular clock to figure out the divergence time of Chimpanzees and humans.

# Define Mutation-selection balance

an equilibrium in the number of deleterious alleles in a population that occurs when the rate at which deleterious alleles are created by mutation equals the rate at which deleterious alleles are eliminated by selection

# Definition the science of improving a population by controlled breeding to increase the occurrence of desirable heritable characteristics

Eugenics

# Define Neutral allele

a form of a gene that when carried in an organism in no way alters the fitness of that individual to survive and reproduce

When you sequence Tibetans, 40% of them have the EPAS1 allele, but only 1-2% of Han Chinese have it. Why do you think the EPAS1 allele is at low frequency in the Han Chinese population?

The same genotype can have different fitness effects in different environments. It may reduce fitness in the environment of the Han Chinese

What is the genomic mutation rate (U) of humans?

~100

# Definition a form of a gene that when carried in an organism in no way alters the fitness of that individual to survive and reproduce

Neutral allele

How do beneficial mutations take over a population?

It starts at a frequency of 1/N. Since it is beneficial, it will increase in frequency with every generation. Eventually, the frequency will hit 1 when it becomes fixed in that population

# Define EPAS1

a type of hypoxia-inducible factor in humans, a group of transcription factors involved in body response to oxygen levels

What is the general equation for the probability of fixation of a new neutral allele?

1/N

# Define Transposon

a chromosomal segment that can undergo transposition, especially a segment of bacterial DNA that can be translocated as a whole between chromosomal, phage, and plasmid DNA in the absence of a complementary sequence in the host DNA

# Define Pseudogenization

The conversion of a gene into a pseudogene

Using a molecular clock, the last common ancestor between humans and chimpanzee is calculated to be 4.28 million years but in reality it is 4.4 million years. Why is there a difference?

* Mutation rates could have changed * Generation times - the per generation mutation rate might be the same, but since humans and chimps have longer generation times, the clock would slow down

What gene do Tibetans have that upregulates genes involved in dealing with hypoxia?

EPAS1

# Definition the process in which two or more populations of an ancestral species accumulate independent genetic changes (mutations) through time, often after the populations have become reproductively isolated for some period of time

Divergence

# Define Genome size (C-value) paradox

Describes the fact that different organisms having the same general level of biochemical, organic, and morphological complexity and even organisms belonging to the same genus, nevertheless often have widely different C-values - the amount of nuclear DNA in the unreplicated gametic nucleus, irrespective of the ploidy level of the species

# Define Genome sequence conservation

the conservation of functionally important DNA sequences by natural selection

Why are we pretty sure that most of the genome is not functional?

1. Genetic load 2. Genome size paradox 3. Genome conservation

# Define Genetic drift

variation in the relative frequency of different genotypes in a small population, owing to the chance disappearance of particular genes as individuals die or do not reproduce

How do you calculate the number of mutations entering a diploid population?

2NU

# Define Subfunctionalization

a neutral mutation process in which each paralog retains a subset of its original ancestral function

In what ways do humans modify their environment to reduce the action of selection?

* Enzyme replacement (i.e. insulin) * Antibiotics * Sanitary living conditions * Detection of heart and vascular defects * Surgery * Fixing of optical disorders

How is parallel evolution related to cancer?

If you look at many tumours that have been treated with the same drug, we see the same mutations arising at rates more often than expected by chance suggesting that they drive resistance

Time to fixation is inversely proportional to what?

Strength of selection