In-Depth Notes on Mutation and Genetic Variation

Coquina Clam (Donax variabilis) and Genetic Variation

• Key Theme: Genetic variation is fundamental to phenotypic variation across organisms.
• Mutations: Novel genetic variations often arise from mutations.

Phenotypic Variation

• Discrete Phenotypic Variation:

  • Caused by single genes having a significant impact (e.g., pigmentation).

• Continuous Phenotypic Variation:

  • Arises from multiple genes, each contributing a small effect to traits (e.g., height).

Genotype vs Phenotype

• Definitions:
  • Genotype: The genetic constitution of an organism.
  • Phenotype: The observable characteristics of an organism.
• Terms:
  • Alleles: Different forms of a gene.
  • Homozygous: Having two identical alleles for a trait.
  • Heterozygous: Having two different alleles for a trait.
  • Polymorphism: Genetic variations observed among individuals of a population.

Example of Genotype and Phenotype

• HERC2 Gene (Chromosome 15):

  • Alleles: C or T at position rs916977.
  • Genotypes: C/C, C/T, T/T.
  • Impacts eye color determined by multiple genetic variants.

• MCM6 Gene (Chromosome 2):

  • Alleles: C or T at position rs4988235.
  • Homozygous and heterozygous configurations: C/C, T/C, T/T.

Genetic Variation in Populations

• Variants can be categorized as common polymorphisms (present in 1% or more of the population) or rare variants (less than 1%). Common variants have significant historical stability while rare variants may have a more recent origin.

Sources of Genetic Variation

• Mutations:

  • Heritable changes in DNA are the primary sources of genetic variation.
  • Mutations can be harmful, beneficial, or neutral.

• Examples of Harmful Mutations:

  • HTT Gene: Mutation leading to Huntington’s disease (expanded glutamine repeat).

• Neutral Mutations:

  • Often found in non-coding regions; do not affect organism fitness (e.g., variations at the PV92 locus).

• Beneficial Variants:

  • Some mutations confer advantages, such as HIV resistance (loss of CCR5 receptor) or lactase persistence in certain populations (allowing digestion of lactose into adulthood).

Lactase Persistence and MCM6 Gene

• The T allele of MCM6 allows expression of lactase beyond infancy, facilitating lactose digestion in certain populations where dairy is a significant food source.

Environmental Interaction with Genotype

• The effect of mutations can often depend on the environment. For instance:
  • β-globin gene (HBB):
  • SS Genotype: Sickle cell disease, harmful in homozygous state.
  • AS Genotype: Sickle cell trait, provides malaria resistance in homozygous state, beneficial in malaria-endemic regions.

Summary of Genotypes Related to Malaria Protection

• C and S Alleles of the β-globin gene:
  • Variant conditions (homozygous and heterozygous states) illustrate differing health impacts, particularly concerning malaria susceptibility.
  • AC heterozygotes show protection against malaria, while CC homozygotes experience less severe anemia but higher malaria risk.

Conclusion

• Genetic variation is complex, involving interactions between mutations, allele variations, and environmental factors. Understanding these interactions is critical for fields such as genetics, evolutionary biology, and medicine.