Molecular Clocks Rose Hoberman

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

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

Rate Constancy? Page & Holmes p240

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

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

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

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

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

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

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

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

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)

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