Chapter 13: Mutation & Genetic Variation

13.1 Genotype and Phenotype

Definitions:

• Genotype/Genome: The genetic makeup of a cell or organism; humans have approximately 3.1 billion base pairs of DNA. Each individual's genotype is unique and consists of all the genes inherited from both parents.

• Phenotype: Observable characteristics of an organism that depend on genotype and environmental influences, including physical traits (like height and eye color) as well as biochemical and behavioral traits.

• Genetic Variation: Differences between individuals in a population; about 0.4% in humans, with approximately 12 million differences in DNA bases. This variation is critical for the process of natural selection and evolution. Human genetic variation is often greater within a racial group than between different racial groups, emphasizing that the concept of “race” is more of a social construct than a distinct biological classification.

• For one gene, diploids (like us) have two copies:

• allele = a particular DNA sequence for that gene

• polymorphism = natural variations in a specific DNA sequence in a population

• silent polymorphisms: no change in amino acid sequence

• neutral polymorphisms: no change in fitness

• mutation = sequence differs from most common genotype

  often used if DNA change leads to abnormal protein function

• homozygous = both copies (alleles) of gene the same

• heterozygous = two alleles different

13.2 Genetic Variation Impact on Fitness

Mutation Outcomes:

• Fitness stays the same: This is the most common outcome where mutations do not affect the organism's ability to survive and reproduce.

• Fitness decreases: Such cases are rare and may lead to reduced reproductive success, often resulting in the diminished frequency of that mutation within the population over generations.

• Fitness increases: These are very rare but critical as they lead to enhanced survival and reproduction. Beneficial mutations may become common in the population over time.

• Evolution: Mutations are essential for evolutionary processes, providing the raw material for natural selection to act upon.

13.3 Alleles and Polymorphisms

• An allele is a specific variant of a gene defined by differences in the DNA sequence.

• Polymorphism refers to the presence of two or more variations (alleles) in a population.Types of Polymorphisms:

• Silent polymorphisms: These do not result in a change in the amino acid sequence, often arising in non-coding regions of DNA.

• Neutral polymorphisms: Do not affect the fitness of the organism, thus have no selective advantage or disadvantage.

• Homozygous: When both gene copies are identical;

• Heterozygous: When two different alleles are present, impacting traits and health risks.

13.4 Genetic Examples

• ABO Blood Type: Different alleles (A, B, O) code for different blood types. These phenotypes are important for blood transfusions and organ transplants but do not have significant fitness effects.

• Taste Receptor Genes: The variation in the TAS2R38 gene affects an individual's ability to taste the bitter compound in broccoli, illustrating how genetic variation can influence dietary preferences and behaviors.

• HTT Gene Mutation: Extensions of the CAG repeat in the HTT gene can lead to Huntington's disease, demonstrating how certain mutations can have severe health impacts, which are often dominantly inherited.

13.5 Beneficial Mutations: Lactase Persistence

• Lactose: A sugar found abundantly in milk; most mammals decrease lactase enzyme production after weaning.

• Some individuals, particularly those with certain genetic backgrounds (such as those of European descent), retain the lactase gene into adulthood due to mutations that enhance gene expression throughout life.

• Lactase Persistence: This phenomenon represents a genetic adaptation in human populations to dairy consumption. Analysis of lactase persistence across different ethnic groups highlights the intersection between genetics and culture, particularly in relation to dietary practices.

13.6 Genetic Differences: Malaria and Hemoglobin

• Hemoglobin Variants:

  • HbA: The normal allele responsible for typical blood function.

  • HbS (Sickle Cell Allele): Provides a selective advantage against malaria in heterozygotes (carriers) while posing serious health risks such as sickle cell anemia in homozygotes (those with two copies of HbS).

  • Variants like HbC also contribute to malaria resistance, showcasing how genetic adaptations can influence health outcomes in response to environmental pressures.

13.7 Nature of Mutations

• Definition: Mutations are heritable changes in genetic material, which occur in the DNA of eukaryotes and prokaryotes, and in RNA for some viruses.

• Mutation Rates: Humans exhibit an average mutation rate of approximately 1 per 10 billion base pairs, reflecting the efficiency and fidelity of DNA replication mechanisms.

• Types of Mutations:

  • Germ-line mutations: Heritable mutations that can be transmitted to offspring;

  • Somatic mutations: Mutations occurring in non-reproductive cells, affecting the individual but not passed to offspring.

• Mutagens: Factors such as UV light and X-rays can increase mutation rates, potentially leading to diseases like cancer.

13.8 Small-Scale Mutations

• Point Mutations: Changes in a single DNA base pair, which can be categorized as silent, missense, or nonsense.

• Silent Mutations: Typically do not alter the amino acid sequence due to redundancy in the genetic code, often occurring in non-coding regions.

• Missense Mutations: A single base change results in a different amino acid; these mutations can lead to conditions like sickle cell disease.

• Nonsense Mutations: Alter an amino acid codon to a stop codon, resulting in truncated proteins that are usually nonfunctional.

• Insertions/Deletions: Larger-scale mutations (involving the addition or loss of nucleotides) can lead to frameshift mutations, significantly impacting protein function and health outcomes.

13.9 Chromosomal Mutations

• Types of Chromosomal Mutations: Include duplications, deletions, and rearrangements, which contribute to genetic diversity and evolutionary processes.

• Copy Number Variation (CNV): Represents variations in the number of copies of particular genes; these variations can have substantial impacts on traits, such as starch digestion efficiency related to dietary habits.

• Forensics Application: Tandem repeats in DNA serve as critical tools for DNA typing and individual identification.

13.10 DNA Damage and Repair

• Mutagens: Can induce various types of DNA damage, including base alterations and strand breaks, increasing the risk of mutations.

• DNA Repair Mechanisms: Errors occurring during replication can be corrected by DNA polymerase proofreading;

• Special enzymes such as BRCA1/2 play vital roles in repairing double-stranded DNA breaks; mutations in these repair genes significantly increase the risk of developing cancers.

• Environmental Factors: Certain lifestyle choices and exposures can influence cancer risks, with genetic predispositions interacting with environmental influences to shape health outcomes.