From: colby@bu-bio.bu.edu (Chris Colby)
Newsgroups: talk.origins
Subject: in defense of directed mutagenesis
Date: 26 Jan 93 20:55:27 GMT
Organization: animal -- coelomate -- deuterostome

In article <1785@tdat.teradata.COM> swf@tools3teradata.com (Stan Friesen) writes:

[much good stuff, not surprizing since it came from Stan, deleted]

>As for the directed mutations in bacteria - if that is indeed shown to be a
>general mechanism of change it *would* cause the rejection of the Darwinian
>model in favor of a new form of orthogenesis.

A quibble: The Darwinian model would be appended, not rejected, if 
directed mutagenesis were to become accepted. Random mutations still
occur, and if they result in a new allele with a different fitness than
the other alleles at the locus in question, natural selection will
occur. The big question, of course, is what is the relative contribution of
the two types of adaptive mechanisms (selection and directed
mutagenesis)?

>But so far it has shown up only in one series of experiments, in one group
>of bacteria, under very odd circumstances.  The effect is not even particularly
>strong - it is barely detectable statistically - which makes it questionable.

Uh... no. It has been shown in _E. Coli_ and _Salmonella typhimurium_ (two
prokaryotes) and _Saccharomyces cerevisae_ (yeast - a eukaryote). Point
mutations, double point mutations and frameshift mutations have all been
shown to revert to "wild type" at a much higher frequency in the
presence of the selective agent than in its absence. Mutation rates
at other loci have been unaffected (i.e. presense of the selective agent
is not a general mutagen). The effects are not small, in one of Hall's
study the mutation rate was 10^8 fold higher than expected under a
random model. Being statistically detectable wasn't a problem.
 
>*If* it is ever confirmed more strongly, *and* is shown to be much more widely
>occuring than is now suggested, it will be time to revise our theories of
>evolution.

IMHO, it is now time to revise our theories of evolution with respect to
single celled organisms (or organisms with totipotent cell lines --
two examples would be plants and sponges). I don't think directed
mutagenesis will work in multicellular organisms with a separate germ
line (again, discounting those with totipotent cell lines), and I
think the opportunity for it to act may be limited. There's no data yet 
on the full range of circumstances directed mutagenesis can occur in.
For example, can dir. mut. do more than fix "broken genes"? -- Can
it come up with novel adaptive solutions to environmental "problems"?
I'm willing to bet yes given the distribution of types of reversion
mutants seen in the dir. mut. studies; both true revertants and
suppresor mutations show up.

It will certainly be interesting to see what the mechanism of
directed mutation (actually, it is mainly going by the name
adaptive mutagenesis these days) is.
 
One of the last couple issues of _Science_ had a review article
critical of directed mutagenesis (Lenski and Mittler, 1993, The
Directed Mutation Controversy and Neo-Darwinism, Science 259: 188-
193). An interesting article (although I'm convinced adaptive
mutations occur) and, if you are unfamiliar with the controversy,
a complete list of the relevant citations. 

On Monday
I'm going to hear a seminar by Pat Foster (who formerly worked with
Cairns) titled something like "The mechanism of adaptive mutation".
If she has found it, I'll relay the news here. However, she was
an author on a recent _Genetics_ paper with roughly the same title and
all they did was rule out some of the proposed mechanisms. (I hope it
isn't Hall's "hypermutable state" model, I bet Larry Moran 10 bucks
that it wasn't 8-)

Stan,
Sorry to jump all over your post, but I really think adaptive
mutation is a potentially important mechanism of evolution.
Time will tell.

>sarima@teradata.com			(formerly tdatirv!sarima)
>  or
>Stanley.Friesen@ElSegundoCA.ncr.com

Chris Colby 	---	 email: colby@bu-bio.bu.edu	---
"'My boy,' he said, 'you are descended from a long line of determined,
resourceful, microscopic tadpoles--champions every one.'"
 	--Kurt Vonnegut from "Galapagos"