RE: Is evolution really the central theory for all of biology?

From: Hofmann, Jim <>
Date: Thu Sep 22 2005 - 11:19:32 EDT



Published online before print September 19, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0501046102
Cell Biology
An evolutionary proteomics approach identifies substrates of the
cAMP-dependent protein kinase

( Ras proteins | sequence conservation | stationary phase )

Yelena V. Budovskaya *, Joseph S. Stephan *, Stephen J. Deminoff, and
Paul K. Herman

Department of Molecular Genetics, Ohio State University, Columbus, OH

Edited by Anthony J. Pawson, University of Toronto, Toronto, ON, Canada,
and approved August 12, 2005 (received for review February 7, 2005)

Protein kinases are important mediators of much of the signal
transduction that occurs in eukaryotic cells. Unfortunately, the
identification of protein kinase substrates has proven to be a difficult
task, and we generally know few, if any, of the physiologically relevant
targets of any particular kinase. Here, we describe a sequence-based
approach that simplified this substrate identification process for the
cAMP-dependent protein kinase (PKA) in Saccharomyces cerevisiae. In this
method, the evolutionary conservation of all PKA consensus sites in the
S. cerevisiae proteome was systematically assessed within a group of
related yeasts. The basic premise was that a higher degree of
conservation would identify those sites that are functional in vivo.
This method identified 44 candidate PKA substrates, 5 of which had been
described. A phosphorylation analysis showed that all of the identified
candidates were phosphorylated by PKA and that the likelihood of
phosphorylation was strongly correlated with the degree of target site
conservation. Finally, as proof of principle, the activity of one
particular target, Atg1, a key regulator of autophagy, was shown to be
controlled by PKA phosphorylation in vivo. These data therefore suggest
that this evolutionary proteomics approach identified a number of PKA
substrates that had not been uncovered by other methods. Moreover, these
data show how this approach could be generally used to identify the
physiologically relevant occurrences of any protein motif identified in
a eukaryotic proteome.


size=2 width="50%" align=left>

Author contributions: Y.V.B., J.S.S., S.J.D., and P.K.H. designed
research; Y.V.B., J.S.S., and S.J.D. performed research; Y.V.B., J.S.S.,
S.J.D., and P.K.H. contributed new reagents/analytic tools; Y.V.B.,
J.S.S., S.J.D., and P.K.H. analyzed data; and Y.V.B., J.S.S., and P.K.H.
wrote the paper.

*Y.V.B. and J.S.S. contributed equally to this work.

To whom correspondence should be addressed.

Paul K. Herman, E-mail: <>

Jim Hofmann




From: [] On
Behalf Of Bill Hamilton
Sent: Thursday, September 22, 2005 6:18 AM
To: Dick Fischer; ASA
Subject: RE: Is evolution really the central theory for all of biology?


Before we leave this topic, at the risk of saying something that has
already been said, here's my take:


I'm probably biased because I'm trained as an electrical engineer --
meaning that my view of the sciences is the so-called "hard" sciences --
chiefly physics. To an individual with a physics bbackground, evolution
looks "messy". If we could have more fossils and could recover more
genetic material from ancient life forms, perhap it wouldn't be so
messy. An article in a now defunct magazine called Scientific Research
~1967 dealt with the Wistar Symposium in which Professor Murray Eden
brought up some mathematical challenges to the theory of evolution. They
interviewed Eden and among other things he mentioned a paper submitted
to one of his colleagues for review. The paper discussed the
evolutionary implications of the dominance of a particular variety of
rodent (I believe) in a particular location. To see what would happen,
Eden changed the variety and circulated the paper to colleagues for
comment. Soon evolutionary explanations came back. The article implied
that t his pointed out a flaw in the theory of evolution. I think it
just points out that evolution is an incomplete model, but still very
useful for understanding how life has developed in a systematic way and
for making some kinds of predictions. It does not now have the precision
of say classical physics, but it is still a useful model. (And we all
know that classical physics is an approximation of relativistic physics
(at high gravity/high speed) and quantum mechanics (at the quantum

Dick Fischer <> wrote:

        Cornelius brought this up:


        ... a paper out of Doolittle's lab has called for a "relaxation
of tree thinking."


        This is a good example of scientists doing what scientists do
and the great unwashed, not steeped in science, reaching errant
conclusions. The "tree of life" with more and more fossils having been
found has developed into more of a "bush." Richard Leakey pointed this
out in his book, Origins Revisited. Note the title of his book. With
new discovery of fossil evidence, branches are reshaped when the
evidence accumulates. No one with any sense denies the
interconnectedness of life, but exactly where and wh en branching
occurred gets revised with new discovery as it should, that's how
science works.


        ~Dick Fischer~ Genesis Proclaimed Association

        Finding Harmony in Bible, Science, and History


Bill Hamilton
William E. Hamilton, Jr., Ph.D.
586.986.1474 (work) 248.652.4148 (home) 248.303.8651 (mobile)
"...If God is for us, who is against us?" Rom 8:31


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Received on Thu Sep 22 11:21:41 2005

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