Folks,

This discussion is now dangerously close to a philosophical discourse
regarding the differences between homoplasy, homology, and analogy. Throw
into the mix synapomorphy and symplesiomorphy - and we've got ourselves a
cladistic analysis soup sprinkled with the croutons of phylogeny.

I do not claim to even be a novice in this field as my knowledge of the
associated science(*) is microscopic -- but I do have a deep respect for the
underlying philosophy, logic, and mathematics and therefore would hazard to
suggest the following:

Maximum likelihood, maximum parsimony, or Bayesian inference (or other
approaches) are all 'apparently good' methods that have found many
practically useful applications. We've adopted many of the terms from
statistics and taxonomy - and sometimes we inadvertently twist their meaning
to the point of error. May we all be forgiven for this - because the
alternative to such lighthearted forgiveness is the requirement for absolute
technical correctness of every piece of scientific text anyone has ever
published. I know that I cannot pass the perfection test, and I do not think
that any of us can, either. I think that we don't just live in glass houses
- a more correct analogy in this case would be houses built of soap bubbles.

With this in mind I'd like to wish us all Happy Holidays (whichever ones you
prefer to celebrate). May your structures grow fat and happy.

Artem

* It is helpful to remember that the terminology we (structural biologists)
use to compare protein structures and sequences is mostly derived from
advanced statistics and taxonomic analysis that both predate structural
biology (in its modern sense) by a fair margin. While it is fun and useful
to assign relationships and build taxonomic trees - it may help to remember
that what we end up with are models and/or estimates. We cannot entirely
avoid bias in taxonomic statistical analysis because optimality criteria are
something we come up with ourselves, and there is no inherent principle by
which they can be judged.

-----Original Message-----
From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of
Douglas Theobald
Sent: Saturday, December 06, 2008 9:12 PM
To: [log in to unmask]
Subject: Re: [ccp4bb] 3D modeling program

----- "Dima Klenchin" <[log in to unmask]> wrote:

>>>But how do we establish phylogeny? - Based on simple similarity!

This is a common, but erroneous, misconception.  Modern phylogenetic
methods (Bayesian, maximum likelihood, and some distance-based) rely on
explicit models of molecular evolution, and the *patterns* of similarity
they create.  Even maximum parsimony, which is not model-based, does not
reconstruct phylogenies based on simple similarity.

>> ah! the old rhetorical trick of changing the problem or question a
>> posteriori! all i pointed out was that things can't be "25%
>> homologous"
>
> Well, you were right that in today's definition things can't be. But
> you seem to be missing my point that today's definition is essentially
> meaningless (relies on circular logic and has no epistemologic value)
> and that nothing would be lost if the term reverted to its generic
> usage, "similar". There would still be a question to be asked "similar
> for what reason?" - same question that is presumed to be answered
> whenever one invokes phylogeny-based homology.

How does this make any sense?  Two proteins can have certain
similarities in sequence (or structure) due to either convergence or
homology.  That is the answer to your question of "similar for what
reason", and hence you have just shown that similarity is not the same
as homology, and that homology is not meaningless.

>> i'm glad your opinion is humble here, because it has much to be
>> humble about :-) do you really think that property (e.g., structure
>> and function) prediction is not useful? and i can't even begin to
>> understand how you can think that 'homology' in its present-day
>> meaning is a pre-darwinian concept.
>
> "Homology" is a pre-Darwinian concept that was *redefined*
> post-Darwin. That's what I wrote.
>
>> okay, so can we all agree now that we won't be saying and writing
>> things like "the two proteins are X% homologous" anymore from now on?
>
> IMHO, it truly does not matter if we do or do not as long as we
> understand each other.

You are hard to understand if you say that two proteins are "25%
homologous".  Do you mean that one domain, out of four, is homologous
between the proteins?  That is the only sense in which that could be
construed as correct.

> Like I wrote in the original reply, paying too much attention to
> definitions of fuzzy abstract concepts is not worth it.

The homology concept is often misunderstood, that is true.  But there
are still blatantly incorrect uses, and substituting "25% homologous"
for "25% similar" is unequivocaly wrong.

An important point to note is that homology must be qualified.  There
are levels of homology, and a structure can be homologous at one level
but not at another.  The classic example is bird and bat wings.  They
are homologous as vertebrate forelimbs, but not as wings.