Molecular clock

Measuring the Rate of Evolution: Molecular Clocks

Evolution at the Molecular Level

  • Definition: Evolution at a molecular level refers to the changes in the genetic material (DNA, RNA, and proteins) that define the evolutionary history of species.

  • Cause of Physical Changes: Physical changes in organisms are caused by mutations at the molecular level.

  • Example of DNA Sequences:

    • Original: ATGTTCTTGCAT

    • Mutated: ATGTCCTTGCAT

    • Additional Mutations:

    • ATGTTCTAGCAT

    • ATATCCTTGCAT

    • ATGTCCTTATAT

    • ACGTTCTAGCAT

    • ATGTTCTAGCGG

How Mutations Arise

  • Types of Mutations:

    • Internal Mutations: Caused by errors in DNA replication and errors that are not repaired.

    • External Mutations: Substantial influence from environmental factors (not detailed here but essential).

Theories for Molecular Evolution

  1. Selection Theory: This theory posits that natural selection drives molecular evolution by favoring beneficial mutations.

  2. Neutral Theory: Suggests that most genetic variations are neutral concerning selection and that factors like genetic drift predominately determine allele frequencies in populations.

  3. Nearly Neutral Theory: A slight variation that posits mutations can be neutral or slightly deleterious, influencing molecular evolution under certain circumstances.

Molecular Clocks (Zuckerkandl and Pauling, 1962)

  • Definition: A molecular clock is a hypothesis stating that DNA and protein sequences evolve at a rate that is constant over time.

  • Proportionality: The genetic difference between any two species is proportional to the time since they shared a common ancestor.

Graph of Evolutionary Divergence (Molecular Divergence Data)

  • Organisms Compared: Human, Macaque, Dog, Bird, Frog, Lamprey.

  • Amino Acid Differences:

    • Examples of differences in hemoglobin polypeptide compared to a human: 132, 45, 67 differences.

    • Graphically represented differences can be understood over an evolutionary timeline, illustrating that larger evolutionary divergence relates directly to the amino acid differences.

Example of Using a Molecular Clock

  • Timeline Scenario:

    • A hypothetical scenario depicts two modern lineages diverging from a common ancestor 50 million years ago. Each mutation leads to an increased genetic difference, showing that after 25 million years there is only a two base difference, and after 50 million years, a four base difference.

  • Key Components:

    • Shared Ancestor: Lived 50 million years ago.

    • Divergence: Accounts for mutations leading to modern differences.

How to Utilize a Molecular Clock

  1. Phylogenetic Relationships: Helps determine how organisms are related.

  2. Calibration with Fossil Records: Fossils provide a timeline that supplies context for DNA risk assessment.

  • Changes:

    • Example: Imagine that there have been 10 changes in DNA between species A and B.

    • Calibration needs to be as accurate as possible to validate evolutionary timelines.

Constructing Evolutionary Stories

  • Evolutionary narratives include hypothesizing mutations over time and linking changes back to common ancestors.

  • Example:

    • If species D has 8 changes from A over 100 million years, E might have similarly sized differences corresponding to mutation rates, which are then represented in an evolutionary tree.

Testing the Molecular Clock

    • Geographical Example: Hawaiian islands demonstrate molecular clocks by studying island age and associated genetic divergence in Honeycreeper species.

      • The Stepping-Stone Model: As the Pacific plate moves over a volcanic hotspot, new islands form in a chronological sequence (e.g., Kauai is older than Maui, which is older than Hawaii). This provides a "natural laboratory" where the geological age of the land provides a maximum age for the species inhabiting it.

      • Genetic Divergence Analysis: Scientists measure the mean $Cytb$ (Cytochrome b) mitochondrial DNA distance between species on different islands.

      • Correlation: Because the timing of island formation is known through potassium-argon dating, the genetic distance (number of mutations) can be plotted against the known age of the islands. If the molecular clock is accurate, the genetic divergence between species on Kauai and Hawaii should be proportionally larger than between species on younger, adjacent islands.

Variability in Molecular Clocks

  • Complexity: Different proteins have distinct rates of evolution.

  • Craig et al. (1993): Suggests that various amino acids can introduce neutrality, where some residues are more critical than others, influencing the evolutionary clock.

  • Generational Effects: Rates of evolution can be slower for species with longer generation times, impacting mutation patterns and synonymous changes.

Evidence of Evolution Constraints

  • Proinsulin studies suggest varying evolutionary rates based on structural complexity among species (e.g., pigs vs. other mammals).

Population Size Influence on Molecular Clocks

  • Population Sizes: Taxa with longer generation spans usually show smaller population sizes, affecting mutation dynamics significantly.

  • Selection vs. Drift:

    • Neutral mutations are influenced by random drift in smaller populations versus selection in larger populations.

Discrepancies in Fossil and Molecular Data

  • Observed Differences: Observations reveal gaps between fossil records and molecular clock estimates, particularly at pivotal evolutionary junctures such as the origin of major animal phyla.

The Relaxed Molecular Clock Theory

  • Definition: Posits that the evolutionary rate can vary among lineages, suggesting variability rather than a constant rate over time.

  • Implications: Highlights that evolutionary rates can be tied to other biological characteristics, adapting through evolutionary pressure.

Practical Applications of Molecular Clocks

  • Contemporary Use: Molecular clocks are useful for studying emerging diseases, with pivotal studies demonstrating their application in understanding viral evolution, such as during the 2009 swine-origin H1N1 epidemic, the COVID-19 pandemic evolution of SARS-CoV-2, and the Ebola virus outbreak in 2014 across the Democratic Republic of Congo.