Sequence redundancy in proteins (was Re: Probability and apologetics )

Terry M. Gray (grayt@Calvin.EDU)
Mon, 4 Sep 1995 11:44:12 -0400

WRT to Glenn's discussion of the number of different sequences that will
produce a given fold.

Mutagenesis studies on proteins of the past 15 years has shown that they
are amazingly resilient to many different substitutions. (This happens to
be my own area of biochemical research. I study the effect of changing the
sequence on changing the fold or structure of the protein.) We and others
doing this sort of research find that for many (if not most) positions you
can substitute several different amino acids in that given position. In
many cases you can substitute every amino acid in particular position. Of
the mutants that have been studied nearly all of them are still functional
in addition to folded because function is selected for or assayed for. Bob
Sauer's group at MIT have systematically substituted every amino acid into
every position into the ~100 residue lambda repressor. They conclude that
there are 10^55 (yes, that's fifty-fifth) different sequences that produce
the functional lambda repressor fold (Reidhaar-Olson and Sauer). The
results of the Brian Matthews lab, our lab and others with T4 lysozyme is
similar.

Interestingly, I've seen at least one creationist turn this argument around
now and say that even if there is 10^55 possible sequences that's still
only one in 10^65 of the possible 10^110 sequences. I reject this argument
as being a problem because it assumes that functional protein sequences are
assembled by random processes which they are not and it denies the efficacy
of selection. Other work from Sauer's lab (Davidson and Sauer) estimates
that 1 in 20 random amino acid sequences produces a folded protein (no
function here). I claim that fold precedes function in evolution and then
with minor (random) tweaking, function and increased stability can be
selected for.

If they are 10^55 possible sequences that produce a single protein, then
there must be exponential orders of magnitude more different possible
sequences that produce a viable E. coli. Frankly, I'm shocked to hear that
Christians have been suggesting that there is only one. On the whole I
find the sorts of arguments made by Thaxton, Bradley and Olsen and others
totally suspect given these results and with Glenn I agree that we are
sadly misguided in our apologetic efforts when we use them. They might
appear convincing to a lay audience, but they are filled with holes.

References

Reidhaar-Olson and Sauer (1990) Proteins: Struct. Funct. Gen., 7:306

Davidson and Sauer (1994) PNAS, 91:2146

Terry G.

_____________________________________________________________
Terry M. Gray, Ph.D. Department of Chemistry and Biochemistry
Calvin College 3201 Burton SE Grand Rapids, MI 40546
Office: (616) 957-7187 FAX: (616) 957-6501
Email: grayt@calvin.edu http://www.calvin.edu/~grayt