Lecture 6: Sources of Genetic Variation: Mutation Flashcards
The genetic substrate for natural selection AND the Raw Material for Evolution
Mutation is the __ __ for natural selection and the __ __ for evolution
- genetic substrate
- raw material
If there is no __ __ neither genetic drift nor natural selection would be able to change allele frequencies, because there would be nothing to change
- genetic variation
Sources of Genetic Variation (2)
- Mutations (changes in the genetic code)
- Sex (Meiosis)
Shuffling of combinations of alleles along a chromosome
Genetic Recombination
Shuffling of combinations of haploid chromosomes into new genotypes
Random Mating
Sex: No novel alleles, only novel __
genotypes
Types of Mutations (4)
1) At the Nucleotide Level (Point mutations)
2) At the “Gene” Level
3) At the Chromosome Level
4) At the Genome Level
Types of mutations at the nucleotide level (point mutations) (3)
– Single nucleotide substitutions (transitions, transversions)
– Insertion (nucleotide insertion)
– Deletion (nucleotide deletion)
Types of mutations at the “gene” level (3)
– Gene Insertions (Gene Duplications, transposons, horizontal gene transfer)
– Gene Deletions (pseudogenization, transposons)
– Exon Shuffling
Types of mutations at the chromosome level (4)
- Chromosome duplications
- Chromosome deletions
- Chromosome inversions
- Chromosome fusions
Types of mutations at the genome level (2)
– autopolyploidization
– allopolyploidization
What are the two main types of mutations within functional coding regions of the genome?
- Structural mutations
- regulatory mutations
What does a structural mutation affect?
It changes the actual coding region of the gene.
A type of mutation within functional coding regions of the genome that changes the actual coding region of the gene.
Structural mutation
A type of mutation within functional coding regions of the genome that alters gene regulation processes, such as gene expression (transcription, RNA processing, translation, etc.).
Regulatory mutation
What are the primary effects of structural mutations? What are the secondary effects of structural mutations?
- Changes in amino acid composition (amino acid substitutions).
- Changes in the secondary, tertiary, and quaternary structure of proteins.
What does a regulatory mutation affect?
It alters gene regulation processes, such as gene expression (transcription, RNA processing, translation, etc.).
__ mutations = single nucleotide change
Point
How do point mutations occur during DNA replication?
Due to errors during mitosis or meiosis by DNA and RNA polymerases, or reverse transcriptase.
How can point mutations arise from repair processes?
Errors in the repair of sites damaged by mutagens, such as UV light or chemicals.
Which type of nucleotide mutations are more common?
Transitions
__ involve mutations between nucleotides of similar structure (purines to purines or pyrimidines to pyrimidines), while __ involve mutations between nucleotides of different structures.
- Transitions
- transversions
What is the difference between transitions and transversions?
Transitions involve mutations between nucleotides of similar structure (purines to purines or pyrimidines to pyrimidines), while transversions involve mutations between nucleotides of different structures.
Why are transitions hypothesized to be less disruptive to DNA structure?
Because transitions involve mutations between nucleotides of similar structure, they cause less disruption of the DNA helical structure and are less detectable by DNA polymerase or mismatch repair enzymes.
How do mutations in RNA codons affect amino acids?
Mutations in positions 1 and 2 often lead to amino acid changes, while mutations in position 3 often don’t matter.
Mutations in positions __ and __ often lead to amino acid changes, while mutations in position __ often don’t matter.
- 1 and 2
- 3
Mutations that lead to amino acid changes, usually occurring in positions 1 and 2 of the RNA codon.
Nonsynonymous Substitutions
What are nonsynonymous substitutions?
Mutations that lead to amino acid changes, usually occurring in positions 1 and 2 of the RNA codon.
What are synonymous substitutions?
Mutations that do not lead to amino acid changes, often occurring in position 3 of the RNA codon.
Mutations that do not lead to amino acid changes, often occurring in position 3 of the RNA codon.
synonymous substitutions
What type of mutations are common sources of new genes?
Gene duplications
A type of mutation that is followed by differentiation between the duplicates, leading to the emergence of new genes
Gene duplications
What term describes the outcome of gene duplications?
Gene family
What are examples of gene families? (3)
- Different opsin genes
- hemoglobin
- ATPases
How can gene duplications occur? (2)
1) “slippage” during DNA replication
2) unequal crossing over during genetic recombination in meiosis.
How often do gene duplications occur per gene per million years? (Lynch and Connery (2000))
0.01 duplications per gene per million years.
What is the half-life for a gene? (Lynch and Connery (2000))
3-8 million years
chromosome segment present in multiple copies
duplication
- repeated segments are adjacent
- often result from unequal crossing-over due to mispairing of homologous chromosomes during meiotic recombination
tandem duplication
Duplicate genes may degenerate into __ (__ __), become __ __, or __ with an existing gene.
- pseudogenes (no function)
- new genes
- subfunctionalize
Fate of duplicated genes (3)
1) nonfunctionalization
2) neofunctionalization
3) subfunctionalization
Examples: Gene Families resulting from gene duplications (9)
- Olfactory receptors
- Steroid hormone receptors
- Heat shock proteins
- Ion uptake enzymes
- Hemoglobins
- Opsins
- Melanins
- Detoxification enzymes (cytochrome P450s)
- Hox genes
A type of mutation: different exons either within a gene or between two nonallelic genes are mixed (end up with new protein)
Exon Shuffling
- DNA sequences that can change their relative position (self-transpose) within the genome.
- “jumping genes”
transposable elements (transposons)
What is the mechanism of transposition for transposable elements? (2)
1) “copy and paste” (retrotransposons)
2) “cut and paste” (DNA transposons).
Who won a Nobel prize in 1983 for the discovery of transposable elements?
Barbara McClintock
What fraction of the genome do transposable elements make up in eukaryotic cells (maize and human genome)? They are often considered as?
They make up a large fraction, often considered “junk DNA,” comprising 85% of the maize genome and 44% of the human genome.
the generation of more than two pairs of homologous chromosomes due to failure of reduction of chromosomes during cell division (mitosis or meiosis).
Polyploidization
the most important and common mechanism of speciation in plants.
Polyploidization
vary among species and even among populations within a species
mutation rates
What causes variation in mutation rates?
Differences in the accuracy of DNA polymerase and the efficiency of DNA repair mechanisms.
Causes of variation in mutation rates: Differences in the accuracy of __ __ and the efficiency of __ __ __.
- DNA polymerase
- DNA repair mechanisms
What is the mutation rate of HIV?
~1 error per 10^4 - 10^5 base pairs per replication cycle
How many cells does HIV infect per day?
~10^9 cells per day
How frequently do all possible point mutations occur in an AIDS patient?
10^4 - 10^5 times per day
How many generations does the virus go through before infecting the next person?
~1000 generations
What is the mutation rate of bacteria?
~1 error per 10^8 - 10^10 base pairs per replication cycle
How many mutations occur per genome per generation in bacteria?
~0.0001 - 0.0002 mutations per genome per generation
What is the mutation rate of Drosophila?
~8 x 10^-11 mutations per base pair per replication cycle
How many mutations occur per genome per generation in Drosophila?
~0.93 mutations per genome per generation
What is the mutation rate of humans?
~ 2 x 10^-8 mutations per base pair per generation
How many new mutations occur per human genome per generation?
~120 new mutations per genome per generation
- Mutation rate varies among species, populations, and even individuals. Why? (3)
1) Genetic Factors - Variation in the accuracy of DNA replication machinery and DNA repair mechanisms among different species and populations.
2) Environmental Factors - Exposure to mutagens such as radiation, chemicals, pollutants, and certain lifestyle factors.
3) Evolutionary Factors - Mutation rates can evolve over time in response to selective pressures and ecological conditions, with natural selection favoring organisms with higher mutation rates under specific environmental conditions.
- How can high mutation rates benefit populations?
provide a constant supply of genetic variation:
- rapid adaptation to changing environmental conditions.
- What is one consequence of high mutation rates?
increase the likelihood of generating beneficial mutations:
- drive evolutionary innovation
- the emergence of novel adaptations.
- What is a drawback of high mutation rates?
increase the frequency of deleterious mutations:
- reduced individual fitness and population viability.
- How can high mutation rates impact genome stability?
may contribute to genomic instability:
- increase the risk of chromosomal aberrations, genetic disorders, and cancer.
- What benefit do low mutation rates provide? (2)
- help maintain genomic stability
- preserve beneficial alleles within populations.
- What is a drawback of low mutation rates?
limit the generation of genetic variation:
- constrains the adaptive capacity of populations.
- How do low mutation rates impact evolutionary dynamics?
slow down the rate of evolutionary change:
- hinders population diversification and speciation processes.
What factors contribute to variation in mutation rates among species and populations?
(1) the accuracy of DNA replication
(2) their abilities to recognize and repair DNA damage
DNA damage and errors occur daily in cells due to occurrences of __ __, __-__ __ __, and __ in DNA replication and meiosis.
- base damage
- single-strand DNA breaks
- errors
Cells utilize DNA repair pathways, such as __ __ of base damage by enzymes (___) and __ of double-strand DNA breaks, to counter the load of DNA damage experienced by the genome.
- direct reversal
- photolyase
- repair
__ __ __ are advantageous when faced with novel or stressful environments, especially in bacteria, as they provide new genetic variation for natural selection to act upon in response to environmental challenges.
Elevated mutation rates
Some bacterial species may evolve “__” __ with elevated mutation rates to cope with environmental stress.
- “mutator” strains
In viruses like HIV, selection may favor __ __ DNA replication systems to elevate the mutation rate, allowing for rapid adaptation to changing environments.
less accurate
The mutation rate is much higher in organelle genomes (mitochondria, chloroplasts) due to the lack of __ __ __.
DNA repair enzymes
parts of the genome where the mutation rate is elevated.
Mutational “hot spots”
Evolutionary causes of mutation rate variation
Hypotheses on mutation rate variation among lineages (not mutually exclusive) (4)
- Generation-time hypothesis
- Metabolic-rate hypothesis
- DNA repair hypothesis
- Genetic drift interfere with selection
What hypothesis? Groups with shorter generations evolve faster due to experiencing more rounds of germ-cell divisions, leading to additional DNA synthesis and more opportunities for mutations.
Generation-time hypothesis
What hypothesis?
- Mutation rate that is due to endogenous or
exogenous mutagens, such as oxygen radicals.
- This hypothesis argues that groups with higher metabolic rates produce more free radicals, which leads to greater DNA damage and faster mutation and evolutionary rates.
Metabolic-rate hypothesis
What hypothesis?
In groups with better DNA repair systems, more mutations are corrected before transmission, which reduces mutational output
DNA repair hypothesis
What hypothesis?
- In smaller populations, selection is less efficient, so fewer deleterious mutations are removed from the genome.
- The end result is an increased presence of deleterious mutations in smaller populations.
Genetic drift interfere with selection
What is the predominant effect of mutations in multicellular eukaryotes?
‘neutral’ with no effect on fitness, as much of the genome is nonfunctional.
What is the typical effect of mutations that affect functional genes?
harmful
Why do mildly deleterious mutations persist longer in a population?
it takes longer for natural selection to remove them from the population.
Why do recessive mutations remain longer in the population?
- they are eliminated when homozygous, not when heterozygous;
- when they are heterozygotes, they are ‘masked’ from selection.
What percentage of the human genome is non-coding sequence?
Up to 95%
Mutations that matter, in an evolutionary sense, are
those that get passed on to the next generation: for example, those that occur in the cells that produce __, known as the “__ __.”
- gametes
- germ line
What happens to mutations that occur in somatic cells?
do not get passed on to the next generation.
How many new mutations occur per individual in humans?
~ 100 or more
How many new deleterious mutations occur per generation in protein-coding sequences?
~1.6
What happens to more harmful, dominant mutations?
get selected out quickly
Would you expect sex differences in mutation rate in the germ line? Why?
Yes. According to the generation-time hypothesis, groups with shorter generations experience more rounds of germ-cell divisions, leading to additional DNA synthesis and more opportunities for mutations due to DNA replication errors. This predicts that the mutation rate for males should be greater than for females due to their greater number of germ-line divisions per generation.
__ __ __, or __-__ __, is the phenomenon where the mutation rate for males is greater than for females due to their greater number of germ-line divisions per generation.
- Male mutation bias
- male-driven evolution
Who discussed the exponential growth of mutations in the male germ line?
James Crow
What is the consequence of males accumulating more mutations?
Males are more likely to pass on genetic diseases, especially with increasing age.
How does egg/sperm production differ between females and males?
Females produce only one set of eggs, while males have ongoing sperm production
Why is the male germline more prone to replication errors?
Due to continuous cell division in sperm production, mutations accumulate exponentially, making the male germline more prone to replication errors.
In __, the mutation rate is constant with age. In __, the mutation rate increases exponentially with age.
- females
- males
Diseases with a strong paternal age effect (12) just give some examples
1) acrodysostosis
*2) achondroplasia
3) Apert syndrome
4) basal cell nevus
5) cleidocranial dysostosis
6) Crouzon syndrome
7) fibrodysplasia ossificans progressive
*8) Marfan syndrome
9) oculodentodigital syndrome
10) Pfeiffer syndrome
*11) Progeria
12) Waardenburg syndrome
How does selection affect allele frequencies? How does selection affect genotype frequencies?
- Selection increases the frequency of advantageous alleles and decreases the frequency of deleterious alleles over time.
- genotype frequencies may shift towards individuals with specific trait combinations favored by selection.
How does genetic drift affect allele frequencies? What is the effect of inbreeding on genotype frequencies?
- Genetic drift can lead to the loss or fixation of alleles over generations, particularly in smaller populations.
- Inbreeding increases the frequency of homozygosity in a population, leading to the expression of recessive alleles and increased prevalence of genetic disorders.
What is the role of recombination in genotype frequencies?
creates new combinations of alleles:
- increase genetic diversity within a population and influencing genotype frequencies.
How does random mating affect allele frequencies?
- maintains allele frequencies constant over generations in the absence of other evolutionary forces.
What is the impact of mutations on allele frequencies?
introduce new alleles into a population:
- increase in genetic variation and potentially leading to changes in allele frequencies over time.
How does migration affect allele frequencies?
results in the transfer of alleles between populations:
- changes in allele frequencies in both source and recipient populations.
What is epigenetic inheritance’s influence on allele frequencies?
can influence gene expression patterns and phenotypic traits without directly altering allele frequencies, but it can affect the response of populations to selection and environmental changes.
What are the sources of genetic variation?
- mutations
- genetic recombination
- gene flow (migration)
- epigenetic modifications
What are the costs and benefits of Sex? Down-side?
the generation of genetic diversity:
- enhances the adaptive potential of populations
- purging of deleterious mutations
down-side:
- energetic investment required for mating
- the risk of sexually transmitted diseases
- loss of genetic material through recombination.
What is the relationship between Genetic Variation and Natural Selection?
Genetic variation provides the raw material upon which natural selection acts. Natural selection acts on heritable variation within populations, favoring individuals with traits that confer higher fitness in a given environment. Genetic variation allows populations to adapt to changing environmental conditions over time through the process of natural selection.
refers to a type of mutation that occurs during DNA replication when the DNA polymerase slips or stutters, resulting in the insertion or deletion of a small number of nucleotides.
slippage
a type of genetic mutation where the addition or deletion of nucleotides in a DNA sequence disrupts the normal reading frame during translation. In simpler terms, it shifts the way the genetic code is read, resulting in a completely different amino acid sequence downstream of the mutation.
frameshift mutation
a type of mutation in DNA that does not result in a change to the amino acid sequence of a protein. This can occur because of the redundancy of the genetic code, where multiple codons can code for the same amino acid.
silent mutation
if a mutation changes one nucleotide in a codon, but the new codon still codes for the same amino acid, then the mutation is silent. Since the amino acid sequence remains unchanged, the resulting protein will likely function normally.
silent mutation
a type of mutation in DNA where a single nucleotide change results in a codon that codes for a different amino acid in the corresponding protein. It can lead to changes in the amino acid sequence of the protein, potentially altering its structure and function.
Missense mutation
This mutation is are implicated in a wide range of genetic disorders and diseases, including inherited conditions like sickle cell anemia and cystic fibrosis, as well as various forms of cancer and neurological disorders. The severity of the effects often depends on factors such as the importance of the affected protein and the specific role of the altered amino acid within its structure or function.
missense mutation
a point mutation that changes a codon that encodes an amino acid into a stop codon, leading to premature termination of protein synthesis.
nonsense mutation
A type of mutation that occurs when one or more nucleotide bases are added into the DNA sequence.
insertion mutation
