The Molecular Clock

Key Points of Investigation:

What is the molecular clock hypothesis? Is it reliable?

  • Molecular clock hypothesis "arises from the observation that the amount of difference between the DNA of two species is a function of the time since their evolutionary separation" (Bromham and Penny)
  • Assumes a relatively constant rate of neutral mutations across species.
    • rates of molecular evolution have been shown to vary 3 ways:
      • changing mutation rates
      • population size
      • selection coefficient
  • Molecular clock definitely varies between taxa (biochemical factors eg. error repair equipment)
  • Challenges some estimated dates of divergence that have been pretty well accepting by biologists/natural historians/archaeologists

Lingering Question: How do you define a mutation as "neutral" before it's undergone selection?

Neutral Mutations

  • Studied by looking at substitutions that occur at sites under no selection constraints
  • Synonymous (silent) substitutions:
    • Nucleotide substitution occurs at third position of codon, and results in the translation of the same amino acid (regardless of NT substitution)
  • Non-synonymous (replacement) substitutions:
    • Nucleotide substitution leads to translation of a different amino acid
  • dN/dS >1: Under neutrality, synonymous sites should evolve fast than non-synonymous sites, so the for a given time period the number of non-synonymous substitution/ number synonymous substitutions should be less than 1 (Week 3: Measuring inter-specific divergence of a protein)

What factors influence "neutral" mutation rates?

  • Codon bias
  • Chromosome location (distance from replication origin in bacteria)
  • Type of substitution (transition vs. transversion)
  • Base composition (Proportions vary across bacterial species)
  • Gene expression ( Mutation rates decrease with levels of gene expression:transcription lowers frequencies of some types of mutations)

Lingering Question: If these factors affect "neutral" mutation rates, is mutation itself undergoing selection?

  • We can expect different proteins and different genes to evolve at different rates because of varying mutational rates

Neutral versus Selectionist Models

  • Neutral Theory: For most proteins, most mutations are neutral and few are advantagous, so rate of molecular evolution depends on the relative proportions of neutral sites
  • Selectionist Theory: All mutations affect fitness, and are therefor either deleterious or advantageous
  • Nearly Neutral Theory: Fate of mutations with slightly positive or negative effects will depend on population size