I think that I am coming across this thread late but I wanted
to add something and I hope it has not already been mentioned.
This is not a new thought but it does seem to bear directly
on this discussion.
One danger in trying to build a comprehensive line of
descent for all proteins using sequence similarity alone
occurs when you reach a certain level of dis-similarity.
The problem is that, by single-mindedly equating
the degree of sequence difference with evolutionary
divergence, you become blinded to the possibility of
evolution by sequence convergence. It is quite possible
that, for some important cellular functions, there are
a few protein motifs that outperform all others. Therefore,
there may be strong selection among some proteins to
develop such a motif. The point is that, in this scenario,
we have proteins becoming more similar in sequence due to
selection over time (i.e., convergent evolution).
This is one of the dangers of using sequence analysis alone
to intuit evolution. More compelling arguments can be
made when the sequence comparisons are used with other
supporting lines of inquiry (like the fossil record,
comparative genetic maps, etc.). Otherwise, I think sequence
difference gives a good estimate of evolutionary distance
but does not necessarily reveal the direction of evolution
(i.e., are the proteins headed their seperate ways or are
they on a collision course?).
Just some thoughts on a Thursday noon,
Professor of Biology