Hi jpnoel1964,

Indeed, HyPhy can do that and more. You can reconstruct ancestral sequences (supplying a protein alignment and [optionally] a tree) using our online server Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login (ASR is the analysis you want). Please let me know if you have any issues running that analysis. My suggestions for running this via datamonkey would be

1). Upload your alignment (make sure you specify that it's a protein alignment)
2). Screen for recombination/gene conversion (unless its biologically improbable)
3). Run the automatic model selection procedure to select the best fitting evolutionary model
4). Run the ASR analysis

HyPhy will return 3 different ancestral reconstructions:

1). Joint: this is the joint assignment of all ancestral characters which maximizes the conditional probability of observing the extant nodes over all possible joint assignments
2). Marginal: this is the character assignment (at a given node) which maximized the probability of the conditional probability given a character at a fixed node (the rest of the tree is 'summed' out)
3). Sampled: samples ancestral characters from the joint distribution in (1); useful for 'noisy' data and to assess reliability.

Be careful with the sites/nodes where the three approaches disagree - there are usually multiple probable reconstructions there.

Sergei

Hi Joe,

You can use both codon and protein sequences and compare the results as a further hedge against reconstruction error. Protein models are actually better for residue reconstruction (in general) because codon models (currently implemented in Datamonkey and almost every other package) do not account for different residue exchangeabilities.

Sergei

Hi Joe,

Could you paste in the URL with model selection results on your data? Model interpretation will be easier on a concrete example.

Sergei

Dear Joe,

The results of the model selection suggest JTT+F (alignment frequencies) as the best fitting model, based on the default criterion (c-AIC). If you click on the [Information/Other analyses] link at the top of the model selection page, and select to run (or re-run) ASR, this model will automatically be filled in for you on the analysis setup page. You can also select other models manually using pull-down menus.

Sergei