Molecular Clocks Rose Hoberman The Holy Grail Fossil

Molecular Clocks Rose Hoberman

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

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

Rate Constancy? Page & Holmes p 240

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 p 229

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 1. Estimate genetic distance d = number amino acid replacements 2. Use paleontological data to determine date of common ancestor T = time since divergence 3. Estimate calibration rate (number of genetic changes expected per unit time) r = d / 2 T

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 p 532

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 for each data set (species/genes) using known date of divergence (from fossil, biogeography) • One calibration point – Rate = d/2 T • 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 p 539 Use multiple genes! (and multiple calibration points)

Even so. . . Be Very Wary Molecular Times Of • 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