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Questions and Answers
To investigate adaptive differences between two closely related species, which approach would be most effective in identifying genomic regions under selection?
To investigate adaptive differences between two closely related species, which approach would be most effective in identifying genomic regions under selection?
- Measuring rates of spontaneous mutations in a laboratory setting.
- Comparing patterns of DNA sequence divergence between the two species. (correct)
- Examining the distribution of phenotypic traits within a population.
- Analyzing allele frequency changes within a single population over a few generations.
In the context of the neutral theory of molecular evolution, what is the primary factor influencing the majority of genetic variation observed within populations?
In the context of the neutral theory of molecular evolution, what is the primary factor influencing the majority of genetic variation observed within populations?
- Migration and gene flow between populations.
- Natural selection favoring advantageous mutations.
- Balancing selection maintaining multiple alleles.
- Mutation and random genetic drift. (correct)
Which of the following best describes the concept of 'DNA polymorphisms' in population genetics?
Which of the following best describes the concept of 'DNA polymorphisms' in population genetics?
- Regions of the genome that do not code for proteins.
- Genetic variations present within a species' population. (correct)
- Fixed genetic differences observed when comparing different species.
- Mutations that always result in a phenotypic change.
What is the key distinction between 'DNA substitutions' and 'DNA polymorphisms'?
What is the key distinction between 'DNA substitutions' and 'DNA polymorphisms'?
Why are synonymous nucleotide substitutions often considered to be nearly neutral in protein-coding genes?
Why are synonymous nucleotide substitutions often considered to be nearly neutral in protein-coding genes?
If approximately 75% of random mutations in a protein-coding gene are nonsynonymous, why do comparisons between species often reveal a lower proportion of nonsynonymous substitutions in functional genes?
If approximately 75% of random mutations in a protein-coding gene are nonsynonymous, why do comparisons between species often reveal a lower proportion of nonsynonymous substitutions in functional genes?
Considering the codon table and genetic code redundancy, what is the approximate ratio of opportunities for nonsynonymous mutations compared to synonymous mutations?
Considering the codon table and genetic code redundancy, what is the approximate ratio of opportunities for nonsynonymous mutations compared to synonymous mutations?
In which genomic region would you expect the ratio of nonsynonymous to synonymous substitutions (Ka/Ks) to be closest to 1?
In which genomic region would you expect the ratio of nonsynonymous to synonymous substitutions (Ka/Ks) to be closest to 1?
The majority of the human genome is characterized as noncoding DNA. What is the implication of this fact for the neutral theory of molecular evolution?
The majority of the human genome is characterized as noncoding DNA. What is the implication of this fact for the neutral theory of molecular evolution?
What is the purpose of the neutral theory of molecular evolution in studies of natural selection?
What is the purpose of the neutral theory of molecular evolution in studies of natural selection?
If a gene has a Ka/Ks ratio significantly less than 1, what is the most likely interpretation regarding the evolutionary forces acting on this gene?
If a gene has a Ka/Ks ratio significantly less than 1, what is the most likely interpretation regarding the evolutionary forces acting on this gene?
In calculating the Ka/Ks ratio, why is the count of synonymous substitutions typically adjusted (e.g., multiplied by 3 in some simplified approaches)?
In calculating the Ka/Ks ratio, why is the count of synonymous substitutions typically adjusted (e.g., multiplied by 3 in some simplified approaches)?
Which of the following Ka/Ks ratios is most indicative of positive selection acting on a protein-coding gene?
Which of the following Ka/Ks ratios is most indicative of positive selection acting on a protein-coding gene?
What is 'purifying selection' and how does it relate to nonsynonymous mutations in functional genes?
What is 'purifying selection' and how does it relate to nonsynonymous mutations in functional genes?
Which statement accurately describes a common misconception about 'purifying selection'?
Which statement accurately describes a common misconception about 'purifying selection'?
Consider a gene with a Ka/Ks ratio of 0.3 in a human-chimpanzee comparison. What evolutionary process is most likely acting on this gene?
Consider a gene with a Ka/Ks ratio of 0.3 in a human-chimpanzee comparison. What evolutionary process is most likely acting on this gene?
What is a 'selective sweep' in population genetics?
What is a 'selective sweep' in population genetics?
What is 'genetic hitchhiking' and how does it contribute to a selective sweep?
What is 'genetic hitchhiking' and how does it contribute to a selective sweep?
What is the expected pattern of genetic diversity in the region surrounding a locus that has recently undergone a selective sweep?
What is the expected pattern of genetic diversity in the region surrounding a locus that has recently undergone a selective sweep?
How does recombination affect the 'footprint' of a selective sweep over time?
How does recombination affect the 'footprint' of a selective sweep over time?
In a genomic scan for selective sweeps, what would be a key signature to look for in population genetic data?
In a genomic scan for selective sweeps, what would be a key signature to look for in population genetic data?
What is the primary difference between a 'hard sweep' and a 'soft sweep'?
What is the primary difference between a 'hard sweep' and a 'soft sweep'?
Why are 'soft sweeps' considered to be potentially more common than 'hard sweeps' in humans?
Why are 'soft sweeps' considered to be potentially more common than 'hard sweeps' in humans?
Which type of selective sweep, hard or soft, typically results in a more pronounced reduction in genetic diversity in the swept region?
Which type of selective sweep, hard or soft, typically results in a more pronounced reduction in genetic diversity in the swept region?
Why might 'soft sweeps' be more challenging to detect in population genomic data compared to 'hard sweeps'?
Why might 'soft sweeps' be more challenging to detect in population genomic data compared to 'hard sweeps'?
Lactase persistence in some human populations is an example of a trait that has likely spread due to a selective sweep. What is lactase persistence?
Lactase persistence in some human populations is an example of a trait that has likely spread due to a selective sweep. What is lactase persistence?
In populations with lactase persistence, what is the typical pattern of homozygosity around the lactase (LCT) gene compared to non-lactase persistent populations?
In populations with lactase persistence, what is the typical pattern of homozygosity around the lactase (LCT) gene compared to non-lactase persistent populations?
The geographic distribution of lactase persistence shows 'hot spots' in certain regions of the world. Which environmental or cultural factor is most strongly associated with the evolution of lactase persistence?
The geographic distribution of lactase persistence shows 'hot spots' in certain regions of the world. Which environmental or cultural factor is most strongly associated with the evolution of lactase persistence?
Regulatory mutations are often implicated in adaptive evolution. In the case of lactase persistence, where are the selective sweep signatures primarily found?
Regulatory mutations are often implicated in adaptive evolution. In the case of lactase persistence, where are the selective sweep signatures primarily found?
A new beneficial allele has recently reached fixation in a population due to a selective sweep. What is your expectation for the level of genetic diversity in the genomic region surrounding this allele?
A new beneficial allele has recently reached fixation in a population due to a selective sweep. What is your expectation for the level of genetic diversity in the genomic region surrounding this allele?
The reduction of genetic diversity near a recently fixed beneficial allele is primarily a consequence of which evolutionary process?
The reduction of genetic diversity near a recently fixed beneficial allele is primarily a consequence of which evolutionary process?
What is the effect of genetic hitchhiking on local genetic variation?
What is the effect of genetic hitchhiking on local genetic variation?
Which of the following is a limitation of using the Ka/Ks ratio to detect selection?
Which of the following is a limitation of using the Ka/Ks ratio to detect selection?
The effectiveness of detecting selective sweeps based on diversity patterns is limited by the time since the sweep event. Why?
The effectiveness of detecting selective sweeps based on diversity patterns is limited by the time since the sweep event. Why?
You are studying a gene and find a Ka/Ks ratio significantly greater than 1. What type of selection is most likely operating on this gene?
You are studying a gene and find a Ka/Ks ratio significantly greater than 1. What type of selection is most likely operating on this gene?
If you hypothesize that a non-coding regulatory region is under positive selection for disease resistance in a human population, which approach would be most appropriate to test this?
If you hypothesize that a non-coding regulatory region is under positive selection for disease resistance in a human population, which approach would be most appropriate to test this?
A strain of bacteria evolves resistance to an antibiotic due to a new mutation. This mutation is strongly beneficial in the presence of the antibiotic. What type of selective sweep is the resistance allele most likely to undergo?
A strain of bacteria evolves resistance to an antibiotic due to a new mutation. This mutation is strongly beneficial in the presence of the antibiotic. What type of selective sweep is the resistance allele most likely to undergo?
In the context of molecular evolution, what does a 'null expectation' typically refer to?
In the context of molecular evolution, what does a 'null expectation' typically refer to?
Which of the following is NOT a limitation of using Ka/Ks ratios to infer natural selection?
Which of the following is NOT a limitation of using Ka/Ks ratios to infer natural selection?
For detecting selection within a species, which approach is generally more informative: divergence-based approaches or population genetic approaches?
For detecting selection within a species, which approach is generally more informative: divergence-based approaches or population genetic approaches?
According to the neutral theory of molecular evolution, what is the expected fate of most new mutations in a population?
According to the neutral theory of molecular evolution, what is the expected fate of most new mutations in a population?
What is the fundamental difference between 'DNA polymorphisms' and 'DNA substitutions' in evolutionary genetics?
What is the fundamental difference between 'DNA polymorphisms' and 'DNA substitutions' in evolutionary genetics?
Why are synonymous mutations considered 'nearly neutral' in the context of protein-coding genes?
Why are synonymous mutations considered 'nearly neutral' in the context of protein-coding genes?
If random mutations are more likely to be nonsynonymous than synonymous, why do we often observe a lower proportion of nonsynonymous substitutions when comparing functional genes between species?
If random mutations are more likely to be nonsynonymous than synonymous, why do we often observe a lower proportion of nonsynonymous substitutions when comparing functional genes between species?
In which type of genomic region would you expect the ratio of nonsynonymous to synonymous substitutions (Ka/Ks) to be closest to 1?
In which type of genomic region would you expect the ratio of nonsynonymous to synonymous substitutions (Ka/Ks) to be closest to 1?
A gene exhibits a Ka/Ks ratio significantly less than 1. What is the most likely evolutionary interpretation?
A gene exhibits a Ka/Ks ratio significantly less than 1. What is the most likely evolutionary interpretation?
When calculating the Ka/Ks ratio, why is the count of synonymous substitutions often adjusted upwards (e.g., multiplied by 3 in simplified methods)?
When calculating the Ka/Ks ratio, why is the count of synonymous substitutions often adjusted upwards (e.g., multiplied by 3 in simplified methods)?
What is 'purifying selection' in the context of molecular evolution?
What is 'purifying selection' in the context of molecular evolution?
How does 'genetic hitchhiking' contribute to a selective sweep?
How does 'genetic hitchhiking' contribute to a selective sweep?
Why are 'soft sweeps' considered potentially more common than 'hard sweeps', especially in humans?
Why are 'soft sweeps' considered potentially more common than 'hard sweeps', especially in humans?
Lactase persistence in human populations is an example of a trait that likely spread due to a selective sweep. What is lactase persistence?
Lactase persistence in human populations is an example of a trait that likely spread due to a selective sweep. What is lactase persistence?
Flashcards
Divergence based approaches
Divergence based approaches
Divergence based approaches look at genetic differences between species, comparing divergence between and within species.
Population genetic approaches
Population genetic approaches
Population genetic approaches analyze genetic variation within a single species to identify selection signatures.
Substitutions
Substitutions
Substitutions are fixed genetic differences observed between different species.
Polymorphisms
Polymorphisms
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Null expectation in evolution
Null expectation in evolution
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Synonymous substitutions
Synonymous substitutions
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Nonsynonymous substitutions
Nonsynonymous substitutions
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Noncoding DNA
Noncoding DNA
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Purifying selection
Purifying selection
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KA
KA
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KS
KS
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KA/KS = 1
KA/KS = 1
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KA/KS < 1
KA/KS < 1
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KA/KS > 1
KA/KS > 1
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Genetic hitchhiking
Genetic hitchhiking
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Selective sweep
Selective sweep
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Genetic diversity during a sweep
Genetic diversity during a sweep
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Classic (hard) sweep
Classic (hard) sweep
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Soft sweeps
Soft sweeps
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Study Notes
- How to detect selection at a locus in the genome involves divergence-based and population genetic approaches.
- Divergence based approaches are between species, and between vs. within species.
- Population genetic approaches are within species.
- Humans and chimpanzees have ~98.77% identical DNA sequences genome-wide.
- In humans and chimpanzees there are ~47 million nucleotide sites that differ.
- Most of the genetic variation in populations results from mutation and genetic drift and not selection, this is The neutral theory
Neutrality
- Most variation within a species is neutral in the form of DNA polymorphisms.
- Most variation between species is neutral in the form of DNA substitutions.
- It is important to find the changes in DNA that are under selection between species
- Substitutions are fixed differences between species. They are a DNA substitution.
- Polymorphisms are within species variation, and are DNA polymorphisms.
Synonymous Substitutions
- Many nucleotide substitutions are synonymous due to the redundancy in the genetic code.
- Many nonsynonymous substitutions have little effect on function or fitness.
- Much of the genome is noncoding, and does not directly encode proteins.
Null Expectation
- The neutral/nearly-neutral theory provides a null expectation for evolutionary patterns present in DNA substitutions between species
- Make predictions under a null model of what types of substitutions might accumulate between species
Positive/Negative Selection
- Neutral/nearly-neutral experiences genetic drift
- Beneficial experiences positive selection
- Deleterious experiences purifying selection
Nonsynonymous Mutations
- About 75% of all mutations are predicted to be nonsynonymous from the codon table.
- All possible mutations in the codon table are about 3x more non-synonymous than synonymous.
- The opportunity for non-synonymous is 3x the opportunity for synonymous substitutions.
- Most functional genes tend to be under purifying selection.
- Purifying selection removes deleterious alleles from the population as well as deleterious nonsynonymous mutations from functional genes to preserve function.
Synonymous vs Non-Synonymous
- At most loci, synonymous substitutions are more common than nonsynonymous substitutions.
- Ka = number of nonsynonymous substitutions
- Ks = number of synonymous substitutions
- The Kₐ/K ratio indicates whether a gene is undergoing positive selection, negative selection, or neutral evolution.
- To calculate the Ka/Ks ratio, you must count the number of synonymous substitutions and multiple them by 3. Why? because approximately 1/3 the opportunity for synonymous mutations to arise compared to nonsynonymous mutations
Kₐ/K ratio
- Kₐ/K = 1 is consistent with purely neutral evolution, and no purifying selection
- Kₐ/K < 1 is consistent with purifying selection, where many amino acid changes are removed by selection
- Kₐ/K > 1 is consistent with positive selection, where multiple amino acid changes favored/fixed by selection
- Purifying selection does not mean that the gene is being purified/removed from the genome, but deleterious alleles are being removed from the population
Limitations of the Kₐ/K ratio
- Using synonymous mutations as neutral sites means that sites are less likely to be adaptive/deleterious on average, but are not truly silent
- Demographic factors can influence power and results
- These are not traditionally used to detect selection on non-coding DNA
Conclusion For Kₐ/K tests
- Tests like Kₐ/K capitalize on comparisons between species to identify coding regions that have evidence of selection.
- Population genetic approaches utilize population level variation (within species) to identify signatures of selection.
Selective Sweep
- Selective sweep is the process through which a new beneficial mutation that increases its frequency and becomes fixed leads to reduction or elimination of genetic variation among nucleotide sequences that are near the mutation
- Genetic hitchhiking is when alleles rise in frequency due to selection at nearby or linked loci under selection.
- Post- selective sweep diversity close to the beneficial mutation is reduced due to hitchhiking.
Lactose Persistence
- Lactase is the enzyme responsible for the digestion of the milk sugar lactose
- Lactase production decreases after the weaning phase in most mammals.
- Regulatory mutations affecting lactase transcription show evidence for a selective sweep
- If not a persistent individual, the average length of the homozygous region is <2000 kb
Selection
- Selective sweeps can be detected through patterns of diversity due to hitchhiking.
- Recent adaptive events leave "footprints” of a sweep because recombination and new mutations break up linkage between alleles over time
- The footprint depends on the strength of selection because stronger selection will lead to faster increase in frequency of beneficial allele, with less time for recombination to break up long haplotypes
Selective Forces
- Classic selective sweeps involve a new, strongly beneficial mutation that increases in frequency to fixation.
- Classic sweeps are rare in humans, but potentially more common in other systems such as Drosophila
- Instead “soft sweeps" appear to be more common, where a previously neutral mutation becomes beneficial due to change in the environment
- The beneficial mutation becomes fixed, and there is still some genetic variation left because the beneficial allele was associated with multiple haplotypes.
- Harder to detect soft sweeps through population genomic data.
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