Ram Samudrala (ram at mbisgi.umd.edu) wrote:
: This is why I initially asked if there was any model that talked about
: evolution in terms of protein structure. ... but I wanted models that
: would describe the probability of a function/structure arising in the
: first place! Even if you use the random mutation mechanism, there
: must be a mathematical model (more complicated than a naive one),...
The fundamental point people miss in probability of evolution arguements
is separability in the problem. The chances of AB evolving de novo as
a functional unit may be very different from the chances of A and B
evolving independently and coming together. We know such events occur
biologically (kinase+Ig->PDGF receptor, kringles+serine protease -> TPA,
innumerable transcription factore examples, ...). There is even evidence
that what we currently think of as domains may have arisen through
aggregation. For example, there is an old paper (JMB ~1976) by Alan
McClachlan identifying a 2-fold axis in the serine proteases and asserting
that they arose by duplication of a primordial domain.
Is there sufficient time/mutations in evolution for a novel small
domain (e.g. zinc finger) to have arisen by chance alone? Sure.
Especially when you consider the extent of sequence variation allowed
within functional copies.
: --Ram
:ram at elan1.carb.nist.gov
David States
Institute for Biomedical Computing / Washington University in St. Louis
Subject: Re: Evolution and Protein Folds
Newsgroups: bionet.molbio.evolution
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Ram Samudrala (ram at mbisgi.umd.edu) wrote:
: This is why I initially asked if there was any model that talked about
: evolution in terms of protein structure. ... but I wanted models that
: would describe the probability of a function/structure arising in the
: first place! Even if you use the random mutation mechanism, there
: must be a mathematical model (more complicated than a naive one),...
The fundamental point people miss in probability of evolution arguements
is separability in the problem. The chances of AB evolving de novo as
a functional unit may be very different from the chances of A and B
evolving independently and coming together. We know such events occur
biologically (kinase+Ig->PDGF receptor, kringles+serine protease -> TPA,
innumerable transcription factor examples, ...). There is even evidence
that what we currently think of as domains may have arisen through
aggregation. For example, there is an old paper (JMB ~1976) by Alan
McLachlan identifying a 2-fold axis in the serine proteases and asserting
that they arose by duplication of a primordial domain. Wally Gilbert
has made similar claims for the globins.
Is there sufficient time/mutations in evolution for a novel small
domain (e.g. zinc finger) to have arisen by chance alone? Sure.
Especially when you consider the extent of sequence variation allowed
within functional domains. Example: suppose a 32 amino acid domain has
4 sites where only a single amino acid is allowed, another 4 sites
where one of 2 are required, 4 sites where one of 4 are required, and
for the remainder, half of the amino acids can be substituted. Odds of
an acceptable sequence arising by chance are one in (20*10*5)**4 * 2**20,
or about one in 10**18. Still seems like a big number, but compared to
the numbers of progeny produced by a liter of culture infected with
bacteriophage, not all that big.
: --Ram
:ram at elan1.carb.nist.gov
David States
Institute for Biomedical Computing / Washington University in St. Louis