Molecular Clock Rate of evolution of DNA is constant over time and across lineages Resolve history of species Timing of events Relationship of species Early protein studies showed approximately constant rate of evolution ID: 332303
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Slide1
Molecular ClockSlide2
Molecular Clock
Rate of evolution of DNA is constant over time and across lineages
Resolve history of species
Timing of eventsRelationship of speciesEarly protein studies showed approximately constant rate of evolutionSlide3
Different rates within a gene or genome
Coding sequences evolve more slowly than non-coding sequences
Synonymous substitutions are often more common than non-synonymous
Some sequences are under functional constraintDifferent genes evolve at different ratesSlide4
Useless concept?
There is no Universal Molecular Clock
Still a very useful concept
Possible to examine both short and long term evolutionary processes by choosing appropriate datasetSlide5
Rates
How do we relate molecular time to geological time?
Calibrate the clock
Lineage divergences in fossil recordMajor geological events causing isolation of populationsContinental drift (Panama Isthmus)Island or lake formationSlide6
Testing the Molecular Clock
Estimate the number of divergences over time
Are these equal for the lineages of interest?
Problem: fossil dating of divergence times is often inaccurate, and not possible for all lineagesCannot measure absolute ratesSlide7
A
B
A
B
A
B
Molecular distance from A to B is the same in all cases
equal
A slower
B slowerSlide8
Relative Rate Test
Sarich & Wilson, 1973
Test
if molecular distance of A to ancestor (circle) is same as B to ancestorMeasure molecular distance from A-O; B-O (sequence substitutions)Distance from A-O should equal B-O
Relative rate
of evolution is the same
A
B
Outgroup (O)Slide9
Testing the Molecular Clock
Compare lineages: is there a “Local clock”?
Hypotheses and mechanisms of clock disruptionSlide10
Local Clocks
Sea urchin species separated by Panama Isthmus
mtDNA divergence constant – obeys clock
Colm O’hUigin (1992) – rates are equal among mouse, rat and hamster lineagesConstant rodent clockSlide11
Humans
versus
monkeys
Slower rate in hominoidsRelative rate test showed that Old World monkey lineage has evolved 1.5 times faster than the human lineageSupported by: genes, pseudogenes, introns, and flanking regionsSlide12
Rodents
versus
primates
Laird et al., 1969Found higher rate of nucleotide substitution between mouse and rat than between human and chimpanzeeGu & Li (1993) – found 600 of 1000 amino acid changes between human and rodent occurred in the rodent lineage
Hypothesise that this was due to a
Generation-time effectSlide13
Sharks
versus
mammals
Sharks appear to be evolving 7-8 times slower than mammalsMetabolic rate hypothesisSlide14
Hypotheses for rate variation
DNA repair efficiency
Generation time effect
Metabolic rate hypothesisSlide15
Generation time effect
Generation time in rodents is much shorter than in humans
Number of germline DNA replication cycles per generation is similar
Rodents have more replication cycles per yearExpect higher mutation rate in short-lived organismsSlide16
Generation time effect
DNA replication is the major source of mutation
An organism with a shorter generation time will undergo more
germ-line cell divisions per yearMales have more germ-line cell divisions than femalesExpect more evolution in the male lineageSlide17
Male-driven evolution
Li
et al.
, (2002) Current Opinion in Genetics and Development 12:650-656Y chromosome is exclusively inherited paternally
X chromosome 1/3 inherited paternally
Compare rates of evolution of X-Y homologues
Male to female ratio of mutation :
Slide18
Testing Male Driven Evolution Hypothesis: Evolutionary approach
Miyata
et al.,
(1987)Ratio of Y/X mutation = 3/(2 + )estimate But limited by available data
Possible to also use autosomes (A)
Y/A = 2/(1 + )
X/A = (2/3)(2 + )/(1 + )
Examine a large number of sites
Accumulation of mutations over long evolutionary timesSlide19
Estimates of
Higher primates:
= 4.2 – 6.3Mice & rats: = ~2
Strong support for male-driven evolution
But …Slide20
Alternative hypothesis
McVean & Hurst (1997)
High
might be caused by reduced mutation on the X (not elevated on Y)Why?X chromosome is hemizygous in malesAll deleterious mutations are exposed to natural selection
Hypothesise: advantageous to have a low mutation rate on XSlide21
Testing the alternative
Birds
Females are heterogametic
Males are homogameticSex chromosome Z is hemizygous in females, not males was estimated as 4-5
Not an artefact of selectionSlide22
Generation-time effect and male-driven evolution
Age of the male should have an effect
Kong
et al. Nature (2012) – older fathers pass on more mutations. Slide23
Metabolic Rate Hypothesis
Sharks appear to be evolving 7-8 times slower than mammals
Metabolic rate hypothesisSlide24
Metabolic-rate hypothesis
Martin & Palumbi (1993)
PNAS
90:4087-4091Strong correlation between substitution rate and body sizeProbably from correlation with generation time and metabolic rateCould explain why whales have a slow substitution rate relative to primates despite their shorter generation time