introduction to molecular dating methods. principles ultrametricity: all descendants of any node are...
TRANSCRIPT
Introduction to molecular dating methods
Principles
• Ultrametricity: All descendants of any node are equidistant from that node
• For extant species, branches, in units of time, are ultrametric
F
BA
10090 80 70 60 50 40 30 20 10
CD
E
Evolutionary branch length
• Expected number of substitutions/site = rate of change x branch duration
• Rate = 0.001 sub/site/Ma
• “True” length = 0.02
• Actual length ≈ 0.02
20 Ma
What is a “molecular clock”?
a) All internodes have equal duration
b) All branches have equal rate of substitution
c) All tips are the same number of time units from the root
d) The expected number of substitutions per site is the same for all branches
e) The observed number of substitutions is the same for all descendants of a given node
The molecular clock idea
• First proposed by Zuckerkandl and Pauling (1965) based on haemoglobin data
• If there is the same rate for all branches there will be a linear relationship between sequence distance and time since divergence
O
B
A
If you know one divergence date then you can calculate others
Per
cent
seq
uenc
e di
verg
ence
Time since divergence
x
y
If you know one divergence date then you can calculate others
Time since divergence
x
z
Per
cent
seq
uenc
e di
verg
ence
Issue 1: There will be error around the estimates
Per
cent
seq
uenc
e di
verg
ence
Time since divergence
x
z
Uncertainty in dating
Stochastic rate variation
Inferred age
Range
Issue 2: You need to correct for multiple hits
Per
cent
seq
uenc
e di
verg
ence
x
z
Assumed re
lationship
Actual relationship
Inferred ageActual age
Issue 3: Is evolution clock-like?
Issue 3: Is evolution clock-like?
Local clock: clade-specific rates
Issue 3: Is evolution clock-like?
No clock: rates vary greatly
Why should we expect a clock?
• Under neutral evolution: but that is too fast for most (all?) data sets
• If there is reasonable constancy of population size, mutation rate, and patterns of selection
• We can hope that rates of evolution change slowly and/or rarely
The likelihood approach
• Consider two models of evolution– The usual model– The same model but
• A root is specified
• The summed branch lengths from any node to all descendants of that node are the same
• Do a likelihood ratio test
Which is the simpler model?
How many degrees of freedom?
• Depends on the number of taxa (n)
• Branch length parameters in the non-clock model = 2n - 3
• Branch length parameters in the clock model = n - 1
• Difference = (2n - 3) - (n - 1) = n - 2
If a clock model is not rejected• Calculate rates and then extrapolate from known
to unknown pairwise distances
DOA = 0.4 ; DAB = 0.1TOA = 90 ; TAB = (0.1/0.4) x 90 = 22.5 Ma
O A B
0.05 0.05
0.195
0.2
90
22.5
Should obtain confidence intervals around date estimates• Look at the curvature of the likelihood
surface (can be done with PAML)
• Use bootstrapping (parametric or non-parametric)– Generate multiple pseudoreplicate data sets– For each data set calculate relative nodal ages– Discard the upper and lower 2.5%
Calibrating the tree
• How does one attach a date to an internal node? How old is the fossil? Where does a fossil fit on the tree?
Calibrating the tree
• How does one attach a date to an internal node? How old is the fossil? Where does a fossil fit on the tree?
F (90 Ma)
What does that tell us?
O
B
AF (90 Ma)
This node is at least 90 Ma
What else?
O
B
AF
This node is at least 90 Ma
This node is more than 90 Ma
The lineage leading to F could have been missed
O
B
AF
This node is at least 90 Ma
General issues
• Fossils generally provide only minimal ages• The age is attached to the node below the
lowest place on the tree that the fossil could attach
• Maximal or absolute ages can only be asserted when there are lots of fossil data
• Geological events can sometimes be used to obtain minimal ages
What if a clock is rejected?
• Until recently three (bad) choices– Give-up on molecular dating– Go ahead and use molecular dating anyway– Delete extra-fast or extra-slow taxa
• Now we have other options– Assume local clocks– Relaxed clock methods
Local clocks
Can use likelihood ratio tests to compare to strict clock and non-clock models
How many parameters?
Non-Parametric Rate-Smoothing(NPRS: Sanderson 1998)
a
d1
d2
The rate of branch a = ra= La/Ta
(L = branch length; T = time duration)
^
Node k
Non-Parametric Rate-Smoothing(NPRS: Sanderson 1998)
a
d1
d2
Measure of rate roughness = Rk = (ra - rd1)2 + (ra - rd2) 2^ ^ ^ ^
Node k
Non-Parametric Rate-Smoothing(NPRS: Sanderson 1998)
a
d1
d2
Adjust times so as to minimize overall roughness:
€
kRk=1
k= n−1
∑
NPRS
• Uses branch lengths only (ignores raw data)
• Quick and easy to do
• Assumes rate change is smooth
Penalized Likelihood(Sanderson 2001)
• Semi-parametric likelihood approach
• Uses raw data but penalizes the likelihood score by the roughness score, , weighted by a smoothness parameter ()
• Selects optimal value of using cross-validation (pick the value that minimizes the errors made in predicting branch lengths)
€
kRk=1
k= n−1
∑
Penalized Likelihood
• Uses more data than NPRS - more accurate
• More difficult to implement