1. The Molecular Clock? By: T. Michael Dodson

2. Hypothesis For any given macromolecule (a protein or DNA sequence) the rate of evolution is approximately constant over time in all evolutionary lineages (Zuckerkandl and Pauling 1965 in Wen-Hsiung Li 1997) Linus Pauling Emile Zuckerkandl

3. Molecular Clock 1960s- Zuckerkandl and Pauling observed that number of amino acid differences between hemoglobins had an approximately linear relationship with the time since the common ancestor (estimated from the fossil record).

4. Neutral Theory Rate of substitution of adaptively equivalent (“neutral”) alleles is precisely the rate of mutation of neutral alleles (Ayala 1999) –Advantageous mutations rare –Deleterious mutations rapidly removed –Leaving “neutral mutations” most prominent This predicts that molecular evolution behaves like a stochastic clock (Ayala 1999) Motoo Kimura

5. Sources of Mutations DNA replication errors DNA damage that is not repaired Bromham and Penny 2003

6. Molecular Clock Converts measures of genetic distance between sequences into estimates of the time at which the lineages diverged (Welch and Bromham 2005) –Uses one or more externally derived date for calibration Fossil Biogeographical –Assumes rate constancy (“Stochastically Constant”) –Every protein and gene is an independent clock (Ayala 1999)

7. Hawaii Honeycreeper Fruitflies Molecular dates form a linear relationship between genetic divergence and time

9. Some date problems Divergence between: –Molecular data against fossil date Marsupials and Eutherians (104 vs. >218 Mya) Humans and gorillas (8 vs. 18 Mya) –Various molecular dates: Rat and mouse –Fossil date = 14 Mya –Molecular date = 33 Mya, 35 Mya, 41 Mya, 42 Mya, and 23 Mya (Pulquerio and Nichols 2006) (Douzer et al. 2003)

10. 7 Calibration points –Together none were congruent with paleontological dates –3 points recovered 2 dates

11. Problems DNA of even closely related species may evolve at different rates (Welch and Bromham 2005) –Mice have consistently faster rates than humans (2:1 synonymous substitutions) (Hermann 2003) –Using a constant rate between “Mice and Men” the molecular date is too old Cladograms based on morphology data and molecular data are only moderately congruent (Hermann 2003)

12. Problems Validity of calibration dates –Fossil date uncertain –Poor sampling –Do not show the oldest ancestor Ayala 1999 –Generation time –Population size –Difference in polymerase ability –Changes in function of protein –Natural selection

13. Conclusions? We cannot expect a universal linear relationship between distance and time Maybe a local molecular may(?) work Maybe Neutral Theory doesn’t work Clocks are still used

14. References F. Ayala (1999), Molecular clock mirages. BioEssays 21: 71-75 L. Bromham and D. Penny (2003), The modern molecular clock. Nature Revies Genetics 4: 216-224 E. Douzery et al. (2003), Local molecular clocks in three nuclear genes: divergence times in rodents and other mammals and incompatibility among fossil calibrations. Journal of Molecular Evolution 57: 201-213 G. Hermann (2003), Current status of the molecular clock hypothesis. The American Biology Teacher 65: 661-663 S. Kumar (2005), Molecular clocks: Four decades of evolution. Nature Reviews Genetics 6: 654-662 W. Li (1997) Molecular Evolution. Sinauer Associates, Sunderland, Massachusetts M.J.F. Pulquerio and R.A. Nichols (2006), Dates from the molecular clock: how wrong can we be? Trends in Ecology and Evolution 22: 180-184 J. Welch and L. Bromham (2006), Molcular dating when rates vary. Trends in Ecology and Evolution 20: 320-327