Pagel's 1994 Correlation method
Peter Midford & Wayne Maddison
The Pagel94 module implements a test of independent evolution
of two binary characters. This test was first described in Pagel
(1994). Although this test has been available in Pagel’s
own program Discrete, this module is not a simple translation
of Discrete. In particular, although the module calculates the
same likelihood value for a given combination of tree and character
states, the maximum likelihood search and character simulation
portions of the module utilize existing Mesquite code. The remainder
of this documentation consists of an overview of the theory of
the test, followed by detailed discussion of the methods used
in the three phases of the test.
Pagel (1994) describes a test of independent evolution of two
binary characters. The test compares the ratio of likelihoods
of two models: one model where the rates of change in each character
are independent of the state of the other and a second model where
rates of change depend on the state of the other character. The
significance of the ratio is tested by comparison with simulated
data, and Pagel warns against using a standard chi-square-based
test in most cases.
The models are expressed as matrices of instantaneous transition
rates, with each row and column specifying a pair of character
states. The model of dependent change specifies 8 parameters and
can be specified by the following matrix:
The zero values on the antidiagonal prevent simultaneous changes
of both characters and the entries on the main diagonal normalize
The model of independent change describes the case where the
transition rates of each variable are independent of the state
of the other. Pagel 1994 describes the independent model as a
pair of 2x2 matrices, one for each variable. The forward (0->1)
and backward (1->0) change rates of each variable are referred
to as alpha and beta respectively. Another approach, taken in
this module is to treat the independent case as a degenerate form
of the dependent model. The model of independent change specifies
4 parameters, which can be obtained from the dependent model by
setting the pairs of parameters across the antidiagonal (q13 and
q24, q12 and q34, q21 and q43, q31 and q42) equal.
Our treatment of the independent (four-parameter) model is different
from Pagel's; we treat it as a version of the eight-parameter
model constrained by setting four pairs of parameters equal (q13=q24,
q12=q34, q21=q43, and q31=q42). Our four-parameter model specifies
that the antidiagonal elements, indicating rates of simultaneous
change, are also zero, in accord with the eight-parameter model
used by us and Pagel. In contrast, Pagel (1994) treats his four-parameter
model differently, as a combination of two separate asymmetric
models, each represented by a 2x2 matrix. Thus, Pagel argues (p.
41) that his four-parameter model is not a constrained version
of the eight-parameter model.
We feel that our formulation of the four-parameter model is a
valid alternative for three reasons. First, it uses the same assumption
(zero rates of simultaneous change) as used in the eight-parameter
model. Second, in our explorations it appeared to arrive at the
same likelihoods as obtained by Pagel's two-asymmetric-model approach.
We have tested the assumption of equivalence numerous times with
both this module and Discrete. Even at high transition rates,
we could find no differences between the two approaches that were
not more appropriately explained as stochastic behavior in the
likelihood searches of the respective programs. This stochastic
behavior can be observed by simply re-running an analysis multiple
times and looking at both the parameter estimates and (especially
for the 8-parameter model) the likelihood values.
Third, setting the anti-diagonals to zero in the four parameter
model appears justified on first principles. As Pagel points out
(p. 40), setting simultaneous rates to zero does not preclude
the possibility of both characters changing state over a longer
period of time. However, because these are instantaneous rates,
the diagonal indicates the rate of events where both characters
change over the same infinitesimal time dt. No matter how large
the rate of character change is, the amount of time spent in transitions
is still zero, thus the chance of two independent characters changing
at the same time is also zero.
To calculate the likelihood of a specific set of rates giving
rise to the observed data at the tips of the particular tree,
the rates must be converted to transition probabilities for each
branch of the tree. Because the model is based on the assumption
of a Markov process, the transition probabilities for a particular
branch are dependent only on the rate matrix and the length of
the branch. The conversion entails calculating exp(lA) where A
is the rate matrix and l is the branch length.
The calculation itself starts from the tips of the tree and works
down each branch toward the root. At each branch the calculated
likelihoods at the upper end are (effectively) multiplied by a
transpose of the transition matrix to obtain the set of likelihoods
at the lower end. The likelihoods at the tips are just the observed
There are several possible ways to combine likelihood calculations
at the root. Currently the module simply adds the likelihoods
for each of the four possible root states to get the overall likelihood
for the model. Other combination options, including weighting
root states empirically from their frequencies at the tips or
by specifying an explicit prior distribution may be made available
in future releases.
The evaluator calculates the likelihood of a specific set of
rates giving rise to the observed data at the tips of the particular
tree. This release uses two methods to calculate the exponentation
of the rate matrix. The first method, which is faster, uses spectral
decomposition (e.g., eigenvalues and eigenvectors). However, this
method does not work correctly when the matrix has complex eigenvalues.
In this case, or any other where the spectral decomposition method
produces a transition probability matrix with negative entries,
the evaluator redoes the calculation using a method first described
by Putzer (1966). This method is slower, but appears to handle
matrices with complex eigenvalues correctly.
The current release does not allow the user to directly specify
a set of parameter values and get a likelihood value. This facility
may be added to future releases.
The Maximum likelihood estimation
To estimate maximum likelihood values for the model parameters,
the Pagel94 module requires an optimizer that works with multiple
variables and does not require derivatives of the function being
optimized. To do this, the module calls on the widely used Brent(1973)
multivariate optimizer. This optimizer has the important property
of not requiring derivatives of the function being maximized.
To improve the chances of finding a global minimum, the module
adds two methods to the optimization process. First the tree is
scaled to a height of one, which reduces the changes of overflow.
Second the module chooses the best result from multiple optimizer
runs starting from different points. For optimizing the independent
(four parameter) model, the module runs the optimizer from three
start points (10, 10, 10, 10), (0.01, 10, 0.01, 10), and (10,
0.01, 10, 0.01).
Because dependent (eight parameter) models generally have more
rugged likelihood surfaces, we found that additional searching
sometimes produced substantially better answers. One example of
this is the great ape data set discussed in Pagel94 and (in expanded
form) in the Discrete manual. To choose multiple starting points,
the model starts by estimating parameters for two six-parameter
models, one where the rates of the first variable is dependent
on the second but rates of the second are independent of the first
(four rates for the first variable + two rates for the second),
and the other with the dependencies reversed. Each six parameter
model is optimized starting from the (saved) optimum of the four
parameter model, with the additional parameters started from initial
values that correspond to the four parameter model. The
search for the eight- parameter model uses multiple start
points derived from the six-parameter model results.
The first two searches start from the values from each of the
six-parameter models. Additional searches, controlled by the Likelihood
iterations command, start from randomized linear combinations
of the values from the six-parameter models. Specifically, the
first four parameters for the eight-parameter search start from
points on the line lying between the corresponding parameters
for the six-parameter models. Because the random element is Gaussian
distributed, the actual start point may lay outside the portion
bracketed by the two values. The remaining four values are set
from a corresponding parameter drawn from one of the six-parameter
models with Gaussian noise added.
Note that the value of additional iteration depends both on the
particular tree and data and on the goal of the analysis. If finding
the best values for the parameters is important, more iteration
will do a more through search of parameter space. If the goal
is simply to perform a test of independence, less iteration and
more simulation is appropriate.
Because Discrete uses a different optimizer than this module,
the likelihoods and parameters found will not be identical in
many cases. For most applications the differences will not be
important. In other cases, the additional search this module provides
should provide more optimal results.
Pagel (1994) strongly recommends testing the observed likelihood
ratios by running Monte Carlo tests using simulated data. Specifically,
for the test of correlated evolution described by Pagel (1994),
the four-parameter model is not exactly a special case of the
eight-parameter model because dual transitions in the rate matrix
(the antidiagonal elements) have been set to zero. Therefore,
Pagel (1994) does not consider a likelihood ratio test based on
a chi-square distribution with four degrees of freedom to be appropriate.
Although a chi-square test might be better justified in Mesquite's
implementation because we use a different four parameter model,
it is unclear how well the chi-square will approximate the correct
distribution at our sample sizes. Thus, we recommend a simulation
as does Pagel.
As discussed above, for estimating statistical significance,
it is better to trade off optimizer iterations for simulation
sets. Note that if the optimizer appears to hang (e.g., neither
progress indicator appears to be updating), it is possible to
abort the simulation. In this case, the module will calculate
Monte Carlo statistics based on however many simulations it did
complete, which might usable in some cases. We recommand for published
results that significance be estimated using 1000 or more simulation
Options for Users
There are three options for users to choose. When first requested,
a dialog box will ask the user for these; once the analysis has
been done, the options can be changed via the Pagel94 menu.
- Extra iterations: as noted above,
the estimation of likelihood of the 8 parameter model can be
requested to use multiple start points. The more start points
specified, the better the estimation of the likelihood should
- Whether to present a P value or not. The
P values are calculated by simulation.
- The number of replicates done in the simulation
to estimate statistical significance. To estimate whether P<
0.05, well over 100 simulations are recommended.
Brent, R. P. 1973. Algorithms for Optimization without Derivatives.
Englewood Cliffs, New Jersey. Prentice Hall.
Pagel, M. 1994. Detecting correlated evolution on phylogenies:
a general method for the comparative analysis of discrete characters.
Proc. R. Soc. London B 255: 37-45.
Putzer, E. J. 1966. Avoiding the Jordan canonical form in the
discussion of linear systems with constant coefficients. American
Mathematical Monthly 73:2-7.