1. Molecular Clocks
Rose Hoberman

2. The Holy Grail
Fossil evidence is sparse and imprecise (or nonexistent)
Predict divergence times by comparing molecular data

3. Given Can we date other nodes in the tree?M
Given
a phylogenetic tree
branch lengths (rt)
a time estimate for one (or more) node
110 MYA
Can we date other nodes in the tree?
Yes... if the rate of molecular change is constant across all branches

4. Rate Constancy?
Page & Holmes p240

5. Protein Variability Protein structures & functions differ
Proportion of neutral sites differ
Rate constancy does not hold across different protein types
However...
Each protein does appear to have a characteristic rate of evolution

6. Evidence for Rate Constancy in Hemoglobin
Large carniverous marsupial
Page and Holmes
p229

7. The Molecular Clock Hypothesis
Amount of genetic difference between sequences is a function of time since separation.
Rate of molecular change is constant (enough) to predict times of divergence

8. Measuring Evolutionary time with a molecular clock
Estimate genetic distance
d = number amino acid replacements
Use paleontological data to determine date of common ancestor
T = time since divergence
Estimate calibration rate (number of genetic changes expected per unit time)
r = d / 2T

9. Poisson Variance (Assuming A Pefect Molecular Clock)
If mutation every MY
Poisson variance
95% lineages 15 MYA old have 8-22 substitutions
8 substitutions also could be 5 MYA
Molecular Systematics p532

10. Need for Calibrations Changes = rate*time
Can explain any observed branch length
Fast rate, short time
Slow rate, long time
Suppose 16 changes along a branch
Could be 2 * 8 or 8 * 2
No way to distinguish
If told time = 8, then rate = 2
Assume rate=2 along all branches
Can infer all times

11. Estimating Calibration Rate
Calculate separate rate for each data set (species/genes) using known date of divergence (from fossil, biogeography)
One calibration point
Rate = d/2T
More than one calibration point
use regression

12. Calibration Complexities
Cannot date fossils perfectly
Fossils usually not direct ancestors
branched off tree before (after?) splitting event.
Impossible to pinpoint the age of last common ancestor of a group of living species

13. Multiple Gene Loci
“Trying to estimate time of divergence from one protein is like trying to estimate the average height of humans by measuring one human”
--Molecular Systematics p539
Use multiple genes!
(and multiple calibration points)

14. Even so... Be Very Wary Of Molecular Times
Point estimates are absurd
Sample errors often based only on the difference between estimates in the same study
Even estimates with confidence intervals unlikely to really capture all sources of variance