The History in Our Genes

The History in Our Genes

Students’ Learning Objectives

  • Describe different types of DNA segments evolve at different rates
  • Explain the importance of selecting appropriate genetic material for molecular clock studies
    • In estimating divergence time
  • Describe the use of dN/dS for testing natural selection

Molecular Clock Concept

  • Different types of DNA segments evolve at different rates
    • Pseudogenes
      • Evolve faster than non-synonymous sites in protein coding genes
      • Do not contribute to an organism’s fitness, leading to higher tolerance for mutations
    • Synonymous Sites
      • Also known as silent mutations
      • Typically evolve faster compared to nonsynonymous sites because these mutations usually do not affect protein function
    • Nonsynonymous Sites
      • Evolve more slowly because most amino-acid-changing mutations are deleterious
      • Selection processes eliminate these harmful mutations from the population

Selection of Genetic Material for Molecular Clock Studies

  • Importance of selecting the appropriate genetic material

    • To measure divergence time of species separated by hundreds of millions of years:
      • A slow-evolving segment of DNA is required for accuracy
      • Fast evolving genes may experience more substitutions at a site over time, leading to substitution saturation
      • Substitution saturation results in misleading nucleotide difference estimates

  • Estimating shorter divergence time

    • Faster evolving genes are necessary
      • Slower evolving genes may not have accumulated any mutations since the divergence effectively occurred recently

Determining the Origins of the Human Immunodeficiency Virus (HIV)

  • HIV Classification

    • Belongs to the group known as lentiviruses
    • Lentiviruses can infect various mammals, including cats, horses, and primates
    • HIV is most closely related to Simian Immunodeficiency Virus (SIV) that infects monkeys and apes

  • Origin Details of HIV

    • HIV-1 Groups M and N
      • Both evolved from a subspecies of chimpanzee, P. t. troglodytes
    • HIV-1 Groups O and P
      • SIV jumped from chimpanzees to gorillas, followed by an adaptation process in gorillas
      • Represents two independent animal-to-human transmission events

dN/dS Testing for Natural Selection

  • Understanding dN/dS

    • The ratio compares the number of nonsynonymous substitutions per nonsynonymous site (denoted as dN) to the number of synonymous substitutions per synonymous site (denoted as dS)
    • A pseudogene is non-functional regarding coding; hence selection cannot act on mutations it acquires
    • Under neutral evolution (no selection present):
      • dN = dS (the number of nonsynonymous substitutions equals the number of synonymous substitutions)

  • Testing for Evidence of Selection

    • Neutral evolution is rejected if nonsynonymous and synonymous substitutions do not occur equally
    • For a gene under positive selection:
      • Beneficial alleles become fixed faster than synonymous alleles
      • Resulting in more nonsynonymous mutations relative to synonymous mutations
      • dN > dS indicates positive selection

  • Natural Selection Dynamics

    • Genes may produce proteins that lose functionality if a single amino acid is altered
    • Natural Selection (also known as purifying selection or negative selection) removes harmful mutations lowering fitness
      • Synonymous mutations, however, remain unaffected as they do not alter protein functionality, thereby allowing them to frequently occur
      • Resulting in dS > dN

Example Question on dN/dS Ratio

  • If strong positive selection occurs in a gene, the resulting dN/dS ratio will show:
    • More synonymous mutations than expected
    • More nonsynonymous mutations than expected
    • An equal number of synonymous and nonsynonymous mutations
    • Positive selection cannot be detected by comparing dN to dS.