The Molecular Clock?

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The Molecular Clock?

• By T. Michael Dodson

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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)

Emile Zuckerkandl
Linus Pauling
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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).

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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
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Sources of Mutations

• DNA replication errors
• DNA damage that is not repaired

Bromham and Penny 2003
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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)

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Hawaii

• Honeycreeper
• Fruitflies
• Molecular dates form a linear relationship
  between genetic divergence and time

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Some date problems

• Divergence between
• Molecular data against fossil date
• Marsupials and Eutherians (104 vs. gt218 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)
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• 7 Calibration points
• Together none were
• congruent with
  paleontological dates
• 3 points recovered
  
• 2 dates

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Problems

• DNA of even closely related species may evolve at
  different rates (Welch and Bromham 2005)
• Mice have consistently faster rates than humans
  (21 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)

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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

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Conclusions?

• We cannot expect a universal linear relationship
  between distance and time
• Maybe a local molecular may(?) work
• Maybe Neutral Theory doesnt work
• Clocks are still used

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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

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