This package is designed specifically for use with RNA sequences that have a
conserved secondary structure, *e.g.*, rRNA and tRNA. It is well known that
compensatory substitutions occur in the paired regions of RNA secondary
structures; this means that substitutions occurring on one side of a pair are
correlated with substitutions on the other side. Most phylogenetic programs
assume that each site in a molecule evolves independently of the others but
this assumption is not valid for RNA genes.

Substitution models of sequence evolution that consider pairs of sites
rather than single sites are implemented in this package along with
standard nucleotides substitution models used nowadays. When a RNA molecule with a secondary
structure is used in conjunction with a RNA substitution model, *PHASE*
requires a structure-based alignment of the sequences with the consensus secondary
structure indicated in bracket and dot notation at the top of the alignment.
We assume that you can provide this structure.

It is now commonplace to perform combined analyses of heterogeneous
sequence data when nucleotides with diffent patterns of evolution
are sequenced for a set of studied species.
It is possible to use several substitution models simultaneously
with *PHASE* (for paired and/or unpaired sites) when analysing protein
coding genes or when stems and loops of RNA genes are used.

*PHASE*
provides a Markov Chain Monte Carlo sampler to generate large numbers of
possible phylogenetic trees with probability proportional to their likelihood.
This is a Bayesian statistical method that allows posterior probabilities to be
generated for alternative trees and alternative clades. These posterior
probabilities provide a sound statistical measure of support of alternative
phylogenetic hypotheses, and they remove the need for bootstrapping. Where many
alternative arrangements of a given set of species exist, it is possible to
calculate posterior probabilities for all the alternative arrangements of these
species in a convenient way.

Standard Maximum Likelihood techniques for inferring the optimal tree with any of the DNA or RNA evolution models are also implemented.

The program's features include:

- Bayesian estimation of phylogenies and substitution model parameters
- standard ML search algorithms for inferring the optimal tree with optional topology constraints
- 6, 7 and 16 state RNA models
- standard 4 state DNA models
- invariant and discrete gamma model for substitution rate heterogeneity between sites
- mixing of molecular data types in a single analysis

Journal publications :

- C. Hudelot, V. Gowri-Shankar, H. Jow, M. Rattray and P. Higgs. ``RNA-based Phylogenetic Methods: Application to Mammalian Mitochondrial RNA Sequences''. Molecular Phylogenetics and Evolution (in press, 2003).
- H. Jow, C. Hudelot, M. Rattray and P. Higgs. ``Bayesian phylogenetics using an RNA substitution model applied to early mammalian evolution''. Molecular Biology and Evolution, 19(9):1591-1601 (2002).