PROCOV

PROtein COVarion analysis

Maximum likelihood estimation of phylogeny under protein covarion models

The covarion hypothesis of protein evolution proposes that selective pressures on an amino acid or nucleotide site change throughout time, rusulting in changes of evolutionary rates of sites along the branches of a phylogenetic tree (W. M. Fitch & E. Markowitz, Biochem. Genet. 4: 479-593, 1970 ). Covarion-like evolution is now recognized as an important mode of molecular evolution in proteins, structural RNA genes and protein-coding genes. Empirical studies have shown that phylogenetic estimation under a covarion model may recover different optimal topologies than when estimation is performed ignoring covarion effects. Simulation studies have demonstrated that under some edge-length conditions, use of rates-across-sites models that ignore covarion effects may cause long branch repulsion biases in the resulting phylogenetic estimates (Wang, Susko, Spencer & Roger, 2008).

PROCOV implements a number of covarion models of protein evolution (Tuffley and Steel, 1998; Galtier, 2001; Huelsenbeck, 2002; Wang et al., 2007). It evaluates the maximum likelihood of a given tree under these covarion models and optimize the tree topology using the subtree pruning and regrafting tree-searching algorithm. Covarion models may be especially useful for phylogenetic estimation when ancient divergences between sequences have occurred and rates of evolution at sites are likely to have changed over the tree. It can also be used to study functional shifts in protein families that result in changes in site-rates in subtrees.

• New version of PROCOV available: Procov_2.0

• Source code

• Test datasets
  

• Features of Procov_2.0 compared with Procov_1.0:
  

• Tree searching available
  
• New user interface - command-line arguments are used
• Three amino acid substitution models available: JTT, WAG and LG
• Implemented numerical libraries (BLAS) for matrix manupulations, increasing procov running speed by about 3-fold.
  
• Can print log likelihoods at sites

• Citations
• Wang H-C, Spencer M., Susko E. & A. J. Roger, Testing for covarion-like evolution in protein sequences. Mol. Biol. Evol. 24: 294-305, 2007. (Proposing a general covarion model and model tests; release Procov_1.0)

• Wang H-C, Spencer M., Susko E. & A. J. Roger, Topological estimation biases with covarion evolution. J Mol Evol.  66: 50-60, 2008. (Simulation studies that show the impact of covarions on phylogenetic inference. Ignoring covarion effects may cause long-branch repulsion bias in phylogeny)

• Wang H-C, Susko E. & A. J. Roger, PROCOV: maximum likelihood estimation of protein phylogeny under covarion models and site-specific covarion pattern analysis. Submitted. (release Procov_2.0; added tree search function and more features)

• PROCOV history:
• January 2009: Procov_2.0 released: Add tree search function to version1.0.

• January 2007: Procov_1.0 released. This version evaluates maximum likelihood for a fixed topology and protein alignment.