Re: true things about evolution (part2)

MikeBGene@aol.com
Sat, 20 Nov 1999 10:13:54 EST

I originally asked:

MB>What's more, life uses only a small subset of all possible
MB>amino acids (only 20; and some of these are thought to have
MB>been acquired into life after its appearance). Given that
MB>abiogenesis experiments produce many other kinds of amino
MB>acids not used by life (often in greater concentrations),
MB>why didn't a life form appear that used these amino acids?

Wesley replied:

WRE>Second possible answer: Perhaps these non-biological amino
WRE>acids also commonly have R-groups that interfere with protein
WRE>stability. If so, then these amino acids would make
WRE>relatively unpalatable "leftovers" for a second or further
WRE>self-replicating system.

I don't think this is a satisfactory answer as there doesn't
seem to be anything special about the R-groups among the
biological amino acids that indicates life exclusively requires
them. Let me point out a few examples:

1. When the Phe in position 3 of arginine vasopressin is
replaced with the unnatural amino acids cyclohexylalanine, norleucine,
or norvaline, it is "well tolerated."

[Stoev S et al. An investigation of position 3 in arginine
vasopressin with aliphatic, aromatic, conformationally-restricted, polar
and charged amino acids. J Pept Sci 1999 Mar;5(3):141-53]

2. Norvaline can globally replace leucine in recombinant
hemoglobin synthesized in E. coli without any dramatic
effect.

[Apostol, I., et al. Incorporation of norvaline at leucine positions
in recombinant human hemoglobin expressed in Escherichia coli.
J. Biol. Chem. 1997 272:28980-8.]

What's interesting about this study is that the amino-acyl
synthetases can misincorporated unnatural amino acids when
charging the tRNA. The tRNA for leucine can be charged
with norvaline and the tRNA for methionine can be charged
with norleucine. Thus any explanation for the origin of the code
better explain how these unnatural amino acids came to be
excluded.

3. With ubiquitin, a highly conserved protein, two core amino acids
were replaced by aminobutyric acid (for Val-26) and norvaline (for
Ile-30) and the product was crystallized. There was a modest change
in conformation and drop in stability, but the biological behaviour of
the modified protein was unaltered.

[Love, SG, et al. Synthetic, structural and biological studies of the
ubiquitin system: synthesis and crystal structure of an analogue
containing unnatural amino acids. Biochem J 1997;323:727-34]

4. Calmodulin is a 148-amino acid protein. In a recent study. up to 90%
of the methionines were replaced with the unnatural amino acids ethionine
and norleucine. These substituted proteins retained their biological
function, showed no change in secondary structure, and, " One- and
two-dimensional NMR studies of the Eth-CaM and Nle-CaM proteins
reveal that, while the core of the proteins is relatively unaffected by
the substitutions, the two hydrophobic interaction surfaces adjust to
accommodate the Eth and Nle residues."

[Yuan T, Vogel HJ. Substitution of the methionine residues of calmodulin
with the unnatural amino acid analogs ethionine and norleucine:
biochemcial and spectroscopic studies. Protein Sci 1999 Jan;8(1):113-21]

I predict that as the field of peptide/protein design grows,
we will find that many unnatural amino acids are easily
tolerated. Right now, mutagenesis with unnatural amino
acids are used to probe conserved sites (using unnaturals
gives the biochemist a broader range of subtlely different
R groups). But I predict that sites which are not conserved
will be incredibly tolerant of unnatural amino acids. In fact,
one day we may be able to design proteins composed
entirely of unnatural amino acids.

The bottom line is that I don't see a good reason for thinking
that an original self-replicating system would drain the
prebiotic earth of all materials that could be used to
spawn a different life form. It seems to me that a rather
large reservoir of left-overs would remain on the plate.
And what's interesting is that in some cases, the
concentration of unnatural amino acids would
apparently be higher than the natural ones. For
example, in spark experiments that mimic a
reducing environment, norvaline is produced
at a yield that is three times higher than valine
and six times higher than leucine. Norleucine
is produced at a yield higher than isoleucine
and methionine is not produced.

MB>It would mean that if bacteria were found on Mars that also
MB>used this same set, we could not use this as evidence that
MB>they are related to Earth forms.

Wesley:

>I would agree on that. More would be needed.

I don't think so. More would be nice, but if
another organism is found that uses the same set of
20 L-amino acids, that's a pretty strong indicator of
a common origin to me.

MB>It would mean that once we begin to explore the universe,
MB>we would expect to find life forms that used this same set
MB>of twenty amino acids.

Wesley:

>I agree again.

Perhaps I should rephrase this. Are you saying that
throughout the universe, if life exists, we should expect
it *all* to be built upon the same set of 20 L-amino acids?

>The specificity that implicates common descent is not the
>particular set of amino acids commonly used in biological
>organisms, but rather in the pattern of association between
>genetic information and those amino acids.

I view it differently. I see several lines of evidence that
implicate descent from a common cause - the same set
of 20 R groups of the amino acids, the same set of five
nitrogenous bases being employed in nucleic acids, the
same set of two sugars being employed in nucleic
acids, AND the universal genetic code.

[I snipped Wesley's demonstration that the genetic
code is just one code among a very, very large
number of possible codes as I am quite aware of
this and have no dispute with this claim.]

MB>And that's the ironic thing about chemical determinism - in
MB>seeking to explain the features of life as chemically
MB>inevitable, it essentially paints all possible life forms
MB>into one category - ours.

Wesley:

>Uh, where's the irony?

To me, the irony is in seeing a chemical determinist
essentially argue that the set of amino acids used
by our life forms are fundamentally special. This is something
I might expect from an ID perspective.

MB>The bottom line is that there would be lots and lots of
MB>leftovers after the "winner takes all."

WRE>The bottom line is that given certain favorable assumptions,
WRE>one could postulate plenty of useful leftovers, while under
WRE>other assumptions favorable to a hypothesis of a single
WRE>earthly abiogenesis event, there may not have been much
WRE>leftover or much leftover of any great utility after the first
WRE>self-replicator made its appearance. While I cannot in
WRE>principle exclude the possibility of multiple origins of life
WRE>on earth, neither am I obligated to accept as a given that
WRE>multiple origins of life actually took place here, contrary to
WRE>the assertion made by Berthajane.

MB>That's fair. But you do then realize that your
MB>winner-take-all scenario is dependent on a small subset of
MB>these assumptions?

Wesley:

>The size of the subset says precisely zip about the likelihood.

Agreed. But since the scenario you paint is dependent on
a small subset of assumptions (meaning its only one of many
possible descriptions), it would be nice if there was some
evidence to back up your scenario.

>Mike left off the part of my post that addressed what he claimed
>was Berthajane's point. I will restore it.

But I didn't think this part addressed what I claimed
Bertvan's point to be. First, Bertvan's point:

BV>In which case, one common ancestor would be obvious. If on
BV>the other hand, life is the inevitable result of
BV>complexity, as Stuart Kauffman suggests, or as Michael
BV>Denton appears to believe, life is a natural phenomenon in
BV>the universe, life must have arisen many times. In that
BV>case one common ancestor (or even 3) would hardly be
BV>likely, would it?

Then, my take:

"I agree with you that there isn't enough evidence to argue
that life must have arisen many times, but I think Bertvan
has a point. With abiogenesis, there are two basic schools
of thought. Christian DeDuve (and I suppose Denton and
Kauffman) favor the view of chemical determinism where,
given the appropriate conditions, abiogenesis is inevitable.
Others view abiogenesis as a highly unlikely event that
depends essentially on the luck of the draw. If the chemical
determinists are correct, we still can't say that life must have
arisen many times, but this does indeed appear to be a natural
implication of this line of thinking. Inevitable things tend
to be likely and likely things tend to happen often. Thus,
I do think the fact that the evidence indicates life is
monphyletic is a real problem for chemical determinism
(but it is not a problem for the lucky accident view).
One can, of course, raise ad hoc scenarios where
the first life forms outcompete subsequent life forms,
but these are easily canceled out by other ad hoc
scenarios where this would not happen."

Now, let's see if what I "left off" is relevant.

>Of course, common descent is not restricted to the idea of a
>single origin of life -- all that common descent requires is
>that modern organisms are derived from one or a few original
>forms (where "few" is whatever number the evidence indicates).
>These may have themselves been derived from the first
>self-replicator, or from a second or subsequent
>self-replicator which eventually displaced its competitors.
>Even if life originated in multiple various forms here on the
>early earth, what the evidence supports is that only one or a
>few closely related instances of these initial systems
>eventually gave rise to all life on earth. The fact of the
>canonical genetic code and the similarity of the genetic
>apparatus across all life argues strongly for a very
>restricted set of common ancestors for all life.

Nope, it's not. Wesley's mistake is in thinking
that Bertvan and I are arguing that common descent
is restricted to a single origin of life. But we are really
arguing from the position of the likelihood of abiogenesis.
If abiogenesis was inevitable, we *expect* multiple
instances of abiogenesis, which would reflect itself as
many very different life forms. No one is saying
it is impossible to raise ad hoc explanations to
account for the fact that the inevitability of abiogenesis
left no trace except for a single, restricted common ancestor.
What this tells me is that the "abiogenesis was likely"
view is not scientific, but rather metaphysical. If
the continued failure to recreate a likely process in the lab
doesn't count against it, and the failure to detect a pattern of
evidence that would reflect this from the past (multiple
life forms) doesn't count against it, then I suppose nothing will
count against it. Perhaps Wesley can spell out the data we could find
that would count against the notion that abiogenesis
was likely.

Mike