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Questions and Answers
What is a significant distinction between germ-line and somatic cells in terms of mutation?
What is a significant distinction between germ-line and somatic cells in terms of mutation?
Which type of mutation is least likely to change the phenotype of an organism?
Which type of mutation is least likely to change the phenotype of an organism?
Which type of mutation is characterized by the insertion or deletion of bases that alters the reading frame?
Which type of mutation is characterized by the insertion or deletion of bases that alters the reading frame?
How does the mutation rate in somatic cells compare to that in germ-line cells?
How does the mutation rate in somatic cells compare to that in germ-line cells?
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What percentage of the genome is affected by important mutations that alter gene function?
What percentage of the genome is affected by important mutations that alter gene function?
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Which type of mutation can result from a coding sequence change leading to a premature stop codon?
Which type of mutation can result from a coding sequence change leading to a premature stop codon?
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What role does xeroderma pigmentosum play in mutation rates?
What role does xeroderma pigmentosum play in mutation rates?
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In what context are most mutations likely to occur within the human genome?
In what context are most mutations likely to occur within the human genome?
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What distinguishes germline mutations from somatic mutations?
What distinguishes germline mutations from somatic mutations?
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What type of mutation is generally considered to be more detrimental?
What type of mutation is generally considered to be more detrimental?
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Which type of mutation introduces a premature stop codon in a protein?
Which type of mutation introduces a premature stop codon in a protein?
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What must occur for a recessive mutation to manifest in an individual's phenotype?
What must occur for a recessive mutation to manifest in an individual's phenotype?
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What is the average rate of spontaneous mutation in the human germ line?
What is the average rate of spontaneous mutation in the human germ line?
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Why are recessive mutations suggested to require inbreeding for expression?
Why are recessive mutations suggested to require inbreeding for expression?
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How do dominant mutations differ from recessive mutations in inheritance?
How do dominant mutations differ from recessive mutations in inheritance?
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Which of the following statements about missense mutations is true?
Which of the following statements about missense mutations is true?
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How many new mutations typically occur in each human child?
How many new mutations typically occur in each human child?
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What is the behavior of a wild type homozygous individual regarding mutations?
What is the behavior of a wild type homozygous individual regarding mutations?
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What is considered a primary effect of mutations on gene expression?
What is considered a primary effect of mutations on gene expression?
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How can a frameshift mutation affect a protein compared to a missense mutation?
How can a frameshift mutation affect a protein compared to a missense mutation?
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Which factor is most influencing the net mutation rate?
Which factor is most influencing the net mutation rate?
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Which of the following scenarios illustrates a homozygous recessive condition?
Which of the following scenarios illustrates a homozygous recessive condition?
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What is the typical cause of frameshift mutations?
What is the typical cause of frameshift mutations?
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What is a common misconception about recessive mutations?
What is a common misconception about recessive mutations?
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Study Notes
Lecture Title and Details
- Lecture 2 of Fundamental Topics in Biology 2X: Molecular Biology I: Mutations
- Given by Prof Joe Gray
- 24th September 2024
FTIB News
- All academic/scientific questions should be posted on the Moodle forum.
- Emails regarding academic/administrative questions will not be answered.
- A set of 3 lectures linked to a lab will come soon.
- Instructions for a take-home essay will appear on Moodle soon.
Aims and Objectives
- Students should be able to outline the nature of mutations.
- Students should be able to outline the basis for and rate of spontaneous mutations.
- Students should be able to outline why most mutations do not affect phenotype, including examples.
- Students should be able to explain the different evolutionary histories of recessive and dominant mutations.
- A large amount of background knowledge of molecular biology and genetics is assumed (ideas, terminology, nomenclature).
- Guidance is given on handling any confusion.
Next 3 Lectures
- Genomes/mutations are fundamental to all of modern biology.
- The aim of the course is to lay a foundation for understanding genomes and mutations.
- Lectures will go beyond rote learning to promote understanding of science as a method of investigation, exploring, and knowledge.
- Scientific knowledge is provisional and ignorance is widespread.
- Familiarity with methods will appear throughout the year.
Three Useful Uni/Life Tips
- Be open to challenges and new people; say yes.
- Move from passive recipient to questioner/critic.
- Find how much time your brain spends actively on a topic and make use of this.
What's in a Genome Sequence?
- Genome sequences contain long strings of DNA bases.
Definitions of Mutations
- Mutations are changes in the genetic material of a cell (or virus).
- A mutation is any heritable alteration in the genetic material.
- Mutations involve changes from one allelic form to another.
Definitions of Mutations cont.
- Focus on how these definitions might vary in different contexts, and the technical terms used in them (allele).
Mutations
- A definition of mutation: "changes in the genetic material of a cell (or virus)."
- Definitions are not necessarily right or wrong, but best fit for a particular situation.
- Genetics traditionally emphasizes heritable mutations in genes.
- Molecular biology can consider all mutations.
- Heritable or not
- Within genes or not
- Affecting the phenotype or not
Definition of Gene
- A gene is a genomic sequence (DNA or RNA) that codes for functional molecules like RNA or proteins.
Background/Spontaneous Mutation
- Natural selection depends on genetic differences. These are generated through sexual reproduction (recombination) and spontaneous mutations.
- The mutation rate is very low (not zero) e.g. for human germ lines ~ 3 new mutations per10^8 base pairs per generation (for 6 billion base pairs diploid).
- There are ~200 new mutations per human child.
- There are ~100 million human births per year.
- There are ~20 billion new mutations per year from the world population.
Net Mutation
- DNA repair works to reduce the net mutation rate.
- DNA damage rate can increase mutation rate.
- Sunbathing
- Holidaying in Chernobyl
- Repair efficiency can be reduced. e.g., bright sunlight.
Germ Line vs. Soma
- Germ line cells pass on genetic information to the next generation.
- Somatic cells are genetic dead-ends (e.g., mutations in somatic cells are not passed on to the next generation).
- Mutation rate is higher in somatic cells.
Mutation Rate in Germ Line vs. Somatic Cells
- Germ line: passes on mutations to the next generation; low mutation rate.
- Somatic: mutations are not passed on to the next generation; higher mutation rate.
Effects of Mutations on Genes
- Most mutations have no effect, particularly if they land in non-coding regions.
- Most random mutations affect unimportant regions of genes.
- Between genes
- Between exons
- Most mutations do not change the phenotype (even if homozygous).
- Mutations will only affect the phenotype if they land on:
- Key functional residues (e.g., protein/RNA coding regions).
- Regulatory regions (gene expression/translation signals, etc.).
Mutations within a Protein-Coding Region
- Types of Point Mutations
- Silent
- Nonsense
- Missense (conservative/non-conservative)
- Frameshift
Mutation within protein-coding region - Analogy
- Wildtype and mutant cases with their corresponding analogy.
Even Small Changes Have Profound Effects
- Small changes in genetic code can drastically alter the meaning of the entire process.
Most Mutations Have No Effect: Mendelian Genetics
- Most mutations, even in important regions, are recessive.
- Recessive mutations can only affect phenotypes when homozygous.
Recessive-Dominance-Heterozygote Behaviour
- Wild-type genotypes always show the wild-type phenotype.
- Homozygous mutant genotypes always show the mutant phenotype.
- Heterozygous genotypes show the wild-type phenotype.
Recessive Mutations and Inbreeding
- For recessive mutations to affect phenotype, inbreeding needs to occur and hence heterozygotes need to fall in love.
- It is not a problem in population of rabbits but a problem in humanity.
- Recessive mutations require inbreeding to show in phenotype.
- Examples of recessive genetic diseases are given.
Thought Experiment: Part A
- Calculate the number of generations between present and some past time.
- Very conservative estimate (33 years per generation) for how many biological ancestors we each had ~500 years ago, and ~1000 years ago.
Thought Experiment: Part B
- Estimate the number of ancestors 500 years ago (1524 CE).
- Historical overview of population (peasants, kings, etc.).
Thought Experiment: Part C
- Estimate the number of ancestors 1000 years ago (1024 CE).
Thought Experiment: Part D
- Estimate the number of ancestors 500 years ago (1524 CE)
- Uses calculation of 20 generations and a world population of ~500 million.
- Conclusion: that number may represent all of humanity.
Thought Experiment: Part E
- Estimate the number of ancestors 1000 years ago (1024 CE), with a historical reference to Malcolm II of Scotland.
Thought Experiment: Part F
- Estimate the number of ancestors 1500 years ago (524 CE).
Thought Experiment: Part G
- Estimate the number of ancestors 2000 years ago (24 CE) and provides a reference to Jesus.
Conclusion
- We are all related, inbred, and mutants, and our ancestors share common ancestry.
References
- Causes & consequences of mutations (Campbell & Reece)
- Modern Genetic Analysis (Griffiths et al.)
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