Download The Molecular Clock?

The Molecular Clock?
By: T. Michael Dodson
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
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).
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
Sources of Mutations
• DNA replication errors
• DNA damage that is not repaired
Bromham and Penny 2003
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)
Hawaii
• Honeycreeper
• Fruitflies
• Molecular dates form a linear relationship
between genetic divergence and time
Some date problems
• Divergence between:
(Pulquerio and Nichols 2006)
– Molecular data against fossil date
• Marsupials and Eutherians (104 vs. >218 Mya)
• Humans and gorillas (8 vs. 18 Mya)
– Various molecular dates:
(Douzer et al. 2003)
• Rat and mouse
– Fossil date = 14 Mya
– Molecular date = 33 Mya, 35 Mya, 41 Mya, 42 Mya, and
23 Mya
• 7 Calibration points
– Together none were
congruent with
paleontological dates
– 3 points recovered
2 dates
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)
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
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
References
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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