clade level molecular clock test?

joe at genetics.washington.edu joe at genetics.washington.edu
Mon Jun 4 12:36:59 EST 2001


In article <9fcmpm$sod$1 at mercury.hgmp.mrc.ac.uk>,
Chris Conroy  <chris.conroy at stanford.edu> wrote:
>   If one suspects that a set of sequences that represent one monophyletic
>clade are evolving at a different rate than a set that represent another
>monophyletic clade, can this be tested in reference to some outgroup(s)? I
>would like to test for a molecular clock (i.e. rate homogeneity) between
>two clades in a maximum likelihood topology rather than two sequences.  I
>don't want to pick a representative of each clade as I might have
>significant amount of rate variation within each of these clades.
>       I'm aware of how to do three-taxon tests with DNA distances (e.g.
>with software like K2WuLi), but I would like to expand that to a larger
>number or use some statistics from the tree itself.  If one were to do all
>the three-taxon comparisons, what would be the most statistically rigorous
>way to combine those results?  One could invoke a two rate model in Yang's
>PAML, but it wasn't clear to me how to test for significance between an ML
>two rate model tree and some other tree (e.g. all rates different or a
>clocklike tree).  Also, PAML does not support all DNA substitution models.

First of all, the way to combine all three-taxon tests is not to do it that
way, but to do an overall likelihood ratio test.  Ideally one would have one
rate, r_1, in clade I and one, r_2 in clade II, and separate rates on each
branch outside the two clades.  The test would compare the likelihood with
r_1 = r_2 to that with them allowed to be different, and it would then have
one degree of freedom.

However, you want to allow rates to differ within each clade as well.  In
that case I can't see what it means to say that the clades are evolving at
the same rate.  Perhaps you mean the rates have different average values.

You aren't going to find a simple option on some program to do this.  The
closest would be to look into the papers on models in which rates are
correlated in neighboring branches, and neither clocklike nor allowed to
vary wildly.  See:

Thorne, J. L., H. Kishino, and I. S. Painter (1998) Estimating the rate of
  evolution of the rate of molecular evolution. Mol. Bio. Evol. 15(12):
  1647-1657. 
Kishino, H., Thorne, J. L., and Bruno, W. J. (2001). Performance of a
  divergence time estimation method under a probabilistic model of rate
  evolution. Molecular Biology and Evolution. 18: 352-361. 
Sanderson MJ.  1997.  A nonparametric approach to estimating divergence times
  in the absence of rate constancy. MOLECULAR BIOLOGY AND EVOLUTION 14:
  1218-1231.
Huelsenbeck JP, Larget B, Swofford D.  2000.  A compound Poisson process for
  relaxing the molecular clock. GENETICS 154: 1879-1892
Bickel DR.  2000.  Implications of fluctuations in substitution rates: Impact
  on the uncertainty of branch lengths and on relative-rate tests. JOURNAL OF
  MOLECULAR EVOLUTION 50: 381-390.
  Mol Biol Evol 2000 Nov;17(11):1647-60
Cutler DJ. 2000.  Estimating divergence times in the presence of an
  overdispersed molecular clock.  Mol Biol Evol  17: 1647-60

Perhaps you will find programs provided by some of these authors.

-- 
Joe Felsenstein         joe at genetics.washington.edu
 Dept. of Genetics, Univ. of Washington, Box 357360, Seattle, WA 98195-7360 USA

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