Re: Article: On the Origins of Chemical Biodefense

On Mon, 17 Oct 2005 00:32:01 -0400 (EDT),
jimmenegay@xxxxxxxxxxxxx <jimmenegay@xxxxxxxxxxxxx> wrote:
> Larry Moran wrote:

[snip]

>> There is a controversy in the field of molecular evolution. Some
>> people, like me, believe that convergence explains many common
>> sequence motifs. We believe it's very unlikely that all traces
>> of sequence similarity could be lost in regions that must preserve
>> structural integrity while randomly changing all the amino acids
>> in order to wipe out sequence similarity. That just doesn't make
>> a lot of sense.
>>
>> Others believe that structural similarity trumps sequence similarity
>> when it comes to making decisions about homology. Those people
>> believe that all similar structures have evolved from a common
>> ancestor. In extreme cases they'll even argue that all zinc
>> fingers and all leucine zippers are homologous.
>>
> Interesting. Could you recommend a review article that discusses
> this controversy? Most of the things I have read say that
> structure is more strongly conserved than sequence and hence
> that structural alignment should guide sequence alignment. I
> had never really considered the possibility of structural
> convergence.

This is one of those "trade secret" things. I hang out with a number
of structural biologists in my department and they all know of the
controversy. That doesn't prevent them from publishing papers that
ignore it. You don't rock the boat if you don't have to.

There are plenty of papers that question individual conclusions of
homology but there aren't many that make the general case. This is
because it's essentially a negative argument. One would have to
publish a paper that merely expressed skepticism concerning hundreds
of papers in the literature and that sort of thing isn't seen to
be productive. The adaptationist paradigm is particularly strong among
biochemists and molecular biologists.

What we need is a novel theory about structural convergence with a
catchy title in order to upset the apple cart and bring the "trade
secret" out into the open. How about "punctuated analogy?"

> But ISTM that 'convergence' is not really a good word for the
> hypothesis. There is no 'gradualism' in the structural
> evolution, is there? The two polymers may evolve to the same
> structure, but they don't really 'converge' upon that structure.
> You almost have to assume that the final structure arises almost
> as a 'saltation'.

Hmmm ... this argument doesn't seem to make any sense. We assume that
all structural motifs originally began as accidental amino acids
sequences that just happened to fold into something useful. Subsequent
evolution refined and modified the structure. Alternatively, the
motif began as something else that was changed by amino acid
substitutions. In either case, the evolution of the structure took
place over a long period of time by successive small changes.

There's no reason why this couldn't have happened several times
independently. That's almost certainly the case with the beta
barrel proteins and the alpha-beta barrel enzymes, for example.

> Which is not to say that it is impossible for two non-homologous
> sequences to have the same structure. When you get right down
> to it, there just aren't all that many different structures to
> choose from.

Right. That's the point. Convergance can't be ruled out so it needs
to be offered as an alternative explanation. It's wrong to conclude
that two proteins are homologous just because they are similar in
structure. That's a unstated assumption that's pervasive in the
scientific literature even though, in private, scientists will admit
that it's just an assumption.



Larry Moran





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