de Duve's "Congruence Principle"



I am reading "Life Evolving" (2002) by Christian de Duve.
"Jake" has previously recommended another de Duve book -
"Blueprint for a Cell" - as an excellent survey of OOL.
I haven't read "Blueprint", but "Life Evolving" seems to
be shallower, broader, and targeted at a more popular
readership. Nevertheless, I find that de Duve has some
interesting things to say.

His basic stance on OOL is heterotrophic and metabolism-first.
He sees the original catalysts for the metabolism as peptides.
In this, he seems to be in the same camp as Dyson, Shapiro,
and Kauffman. But he discusses an idea he calls the
"Congruence Principle" which seems to be quite compatible
with my (and Wachtershauser's) viewpoint. An extended quote:

What must be searched for first is how some sort of
primitive metabolism, a 'protometabolism', could have
arisen spontaneously under prebiotic conditions.

A detailed examination of the chemical reactions that
may have composed protometabolism is out of the question.
Solid knowlege on this subject is virtually nonexistent,
anyway, and the speculations that stand in lieu of it
are almost as numerous and varied as the investigators
interested in the problem. I shall content myself with
a general remark. It expresses a personal and far from
widely accepted opinion, which, however, I will try to
justify later: protometabolic pathways prefigured the
pathways of present-day metabolism. ...

This affirmation, which I have called the 'congruence
principle', implies as an important corollary that
present-day metabolism holds traces of the primitive
chemistry and could serve as a valuable source of
inspiration in the elaboration of theories ...

The main lesson of metabolism [is that] virtually none
of the reactions of metabolism would take place if the
participating substances were merely mixed together.
It is for this reason that most experts are skeptical
of the congruence principle. In their opinion, prebiotic
chemistry, not having available the catalysts of
biochemistry, could not possibly reproduce the reactions
of biochemistry. But one may instead wonder whether
appropriate catalysts could not have been present in
the cradle of life.

Needless to say, the search for possible prebiotic
catalysts has always been an important preoccupation
of origins-of-life investigators. But their search has,
for obvious reasons, been largely restricted to the
mineral world; and it has not been entirely fruitless.

[snip discussion of clays as catalysts of nucleotide
polymerization and of iron-sulfur chystals as catalysts
of redox reactions. Also snip de Duve's ideas that
prebiotic peptides may have functioned as catalysts.]

The justification of the "congruence principle" is given
several pages later as he discusses how modern-day
genetically encoded enzymes might have evolved to replace
the primitive catalysts:

A crucial element of the envisaged scenario is the
need for [new] enzymes to be useful - without which
there could be no selection. In order to be useful,
an enzyme must necessarily have available in its
environment one or more substrates on which to act.
Without substrate, even the most sophisticated catalyst
is valueless. The enzyme must also have an outlet
for the products that it forms, if it is not to run
into a chemical dead end. These substrates and outlets
must have been provided by the primitive metabolism
that supported the protocells at the time. Or, put
differently, and more pertinently, only those enzymes
that found substrates and outlets in the existing
protometabolism could have been retained by selection.
The protometabolism, therefore, acted as a screen for
the first enzymes, which must, by necessity, have fitted
within existing chemistry. This, in my opinion, is
a strong reason for believing that protometabolism
and metabolism were 'congruent', that is, followed
similar pathways.

The case made here is far from airtight. Horowitz, for
example, came up with a scheme whereby metabolic pathways
evolve step-by-step from products to precursors. In
theory, that could work, but when you look at the details
Horowitz's idea seems pretty silly. Still, it is conceivable
that some particular sequence of enzyme origins might
make selective sense.

Furthermore, it may seem that de Duve is just pushing the
problem back in time. His scheme makes the evolution of
enzymes plausible, but it does not explain how a coherent
set of protoenzymes could have arisen (let alone how
that set could be heritable).

To my mind, a stronger reason for believing in some kind
of congruence principle is the need for each step in a
reaction sequence to be both thermodynamically and
mechanistically plausible. There are only so many ways
of getting from point A to point B that don't involve
impossible uphill grades or mechanistically implausible
"tunneling". Superhighways in the American West tend to
follow the same path as earlier roads, railroads, and
ultimately pioneer oxcart trails. According to de Duve,
the same path is followed because that is where the
towns have grown up. According to me, it is because
there is no other good way through the mountains.

In any case, I believe that there is an important grain
of truth in de Duve's congruence principle, and it is one
of the reasons why I believe that a good understanding
of biochemistry is essential to the serious origin-of-life
investigator.





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