How Do We Measure the Past Without a Time Machine?
Molecular Clock
The use of the gradual accumulation of mutations to infer when species diverged from a common ancestor.
- Scientists estimate evolutionary timelines by examining changes in DNA sequences.
- This technique is called the molecular clock.
Imagine trying to estimate the time between two old family photos by observing visible changes like aging.
Why Sequence Differences Matter
- DNA encodes proteins, so changes in DNA often result in changes in amino acid sequences.
- The greater the number of differences in homologous DNA or protein sequences between two species, the longer the time since they diverged.
- These differences arise through mutations: base substitutions, insertions, or deletions.
In IB exams, you must explicitly state that differences accumulate gradually and are assumed to occur at a relatively constant rate in the molecular clock model.
Basis of the Molecular Clock
- Mutations introduce changes in nucleotide base sequences of DNA.
- Some mutations alter amino acid sequences in proteins, while others may be silent.
- Over time, differences accumulate in genomes between lineages that no longer interbreed.
- The greater the number of sequence differences, the longer ago the species diverged.
- These differences can be quantified and used as an approximate measure of evolutionary time.
Always state that the molecular clock provides estimates, not exact dates, because mutation rates are not perfectly constant across species or environments.
Factors Affecting the Rate of Accumulation
- Generation time: species with shorter generations (e.g., bacteria, viruses) accumulate mutations faster due to more replication cycles.
- Population size: large populations retain more genetic variants, while small populations may lose mutations due to genetic drift.
- Selective pressure: harmful mutations are often removed, while neutral mutations accumulate.
- DNA repair mechanisms: species with efficient repair enzymes accumulate fewer mutations; those lacking proofreading accumulate more.
RNA viruses like influenza and HIV evolve extremely rapidly because their polymerases lack proofreading functions, leading to very high mutation rates.
Applications of the Molecular Clock
1. Human and Primate Evolution
- Human–chimpanzee split estimated at ~4.5–6 million years ago.
- Chimpanzee–bonobo split estimated at ~1 million years ago.
- Mitochondrial DNA (mtDNA) used to trace the most recent common ancestor (MRCA) of humans, sometimes called “Mitochondrial Eve,” living about 150,000 years ago.
mtDNA is especially useful because it is inherited only maternally, does not recombine, and mutates at a relatively steady rate.
2. Example: Cytochrome c and Cytochrome Oxidase
- Highly conserved proteins like cytochrome c (respiration) are compared across species.
- Fewer differences result in more recent common ancestor.
- Used to settle classification controversies (e.g., tarsiers).
Cytochrome oxidase subunit I (COX1) is widely used as a DNA barcode for identifying species and inferring evolutionary relationships.
3. Constructing Phylogenetic Trees
- Differences in DNA/protein sequences allow scientists to build phylogenetic trees.
- Branch lengths correspond to estimated divergence times.
If asked to interpret a phylogenetic tree based on molecular data, explain both relatedness (closer branches = more recent ancestor) and time estimates (based on number of differences).
DNA vs. Protein Sequence Data
- DNA sequence comparisons: Detect even silent (synonymous) mutations that do not change amino acids.
- Protein sequence comparisons: More conserved, useful for comparing distantly related species (e.g., cytochrome c, haemoglobin).
- Both approaches can be combined for higher accuracy in building phylogenetic trees.
Limitations of the Molecular Clock
- Mutation rates are not perfectly constant.
- Some DNA regions mutate faster than others.
- Environmental conditions, selection pressures, and life history traits can accelerate or slow mutation accumulation.
- Therefore, the molecular clock provides only approximate estimates, not precise times.
Because of these limitations, biologists often use multiple genes and compare results to improve accuracy.
Theory of KnowledgeHow does the assumption of a constant mutation rate reflect the limitations of scientific models? Can you think of other scientific fields where simplifying assumptions are necessary but imperfect?
Self review- What is the molecular clock, and how is it used to estimate divergence times?
- Describe two biological factors that influence mutation rates and how they affect the molecular clock.
- Explain how mitochondrial DNA can be used to trace human ancestry.


