"Binary" Enzyme Demonstrates Darwinian Evolution at its
By Jason Socrates
Two scientists at The Scripps Research Institute (TSRI),
Research Associate John S. Reader and Professor Gerald F.
Joyce both of the institute's Department of Molecular Biology,
have succeeded in creating an enzyme based on a "binary" genetic
codeone containing only two different subunits.
This research, described in the latest issue of the journal
Nature, demonstrates that Darwinian evolution can occur
in a genetic system with only two bases, and it also supports
a theory in the field that an early form of life on earth
may have been restricted to two bases.
"Nobody will ever top this because binary systems are the
most reduced form of information processing," says Joyce.
"Two different subunits are the absolute minimum number you
need [for Darwinian evolution]."
Where protein enzymes are polymer strings made up of 20
building blocks (the amino acids), and RNA or DNA enzymes
are made up of four different building blocks (the nucleotides),
the world's first binary enzyme has but two different building
blocks, based on the nucleotides A and U.
This enzyme is functionally equivalent to a "polymerase"
molecule. Polymerases are ubiquitous in nature as the enzymes
tasked with taking a "template" string of DNA or RNA bits
and making copies of it.
Reader and Joyce's binary enzyme is able to join pieces
of RNA that are composed of the same two nucleotide symbols.
In the test tube, the binary string folds into an active three-dimensional
structure and uses a portion of this string as a template.
On the template, it "ligates," or joins subunits together,
copying the template.
Experimental Approaches to the Origins of Life
If the origins of life are a philosopher's dream, then they
are also a historian's nightmare. There are no known "sources,"
no fossils, that show us what the very earliest life on earth
looked like. The earliest fossils we have found are stromatoliteslarge
clumps of single-celled bacteria that grew in abundance in
the ancient world three and a half billion years ago in what
is now western Australia.
But as simple as the bacteria that formed stromatolites
are, they were almost certainly not the very first life forms.
Since these bacteria were "evolved" enough to have formed
metabolic processes, scientists generally assume that they
were preceded by some simpler, precursor life form. But between
biological nothingness and bacteria, what was there?
Far from being the subject of armchair philosophy or wild
speculation, investigating the origins of life is an active
area of research and of interest to many scientists who, like
Reader and Joyce, approach the questions experimentally.
Since the fossil record may not show us how life began,
what scientists can do is to determine, in a general way,
how life-like attributes can emerge within complex chemical
systems. The goal is not necessarily to answer how life did
emerge in our early, chemical world, but to discover how life
does emerge in any chemical worldto ask not just what
happens in the past, but what happens in general.
The most important questions are: What is feasible? What
chemical systems have the capacity to display signs of life?
What is the blueprint for making life in the chemical sense?
One of the great advances in the last few decades has been
the notion that at one time life was ruled by RNA-based lifean
"RNA world" in which RNA enzymes were the chief catalytic
molecules and RNA nucleotides were the building blocks that
stored genetic information.
"It's pretty clear that there was a time when life was based
on RNA," says Joyce, "not just because it's feasible that
RNA can be a gene and an enzyme and can evolve, but because
we really think it happened historically."
However, RNA is probably not the initial molecule of life,
because one of the four RNA bases"C"is chemically
unstable. It readily degrades into U, and may not have been
abundant enough on early Earth for a four-base genetic system
to have been feasible.
Odd Base Out
To address this, Nobel laureate Francis Crick suggested
almost 40 years ago that life may have started with two bases
instead of four. Now Reader and Joyce have demonstrated that
a two-base system is chemically feasible.
Several years ago, Joyce showed that RNA enzymes could be
made using only three bases (A, U, and G, but lacking C).
The "C minus" enzyme was still able to catalyze reactions,
and this work paved the way for creating a two-base enzyme.
In the current study, Reader and Joyce first created a three-base
enzyme (A, U, G) and then performed chemical manipulations
to convert all the A to D (diaminopurine, a modified form
of A) and biochemical manipulations to remove all the G. They
were left with an enzyme based on a two-letter code (D and
Reader and Joyce insist that their study does not prove life
started this way. It does, however, demonstrate that it is
possible to have a genetic system of molecules capable of
undergoing Darwinian evolution with only two distinct subunits.
The article, "A ribozyme composed of only two different
nucleotides," was authored by John S. Reader and Gerald F.
Joyce and appears in the December 19, 2002 issue of the journal
This work was supported by a grant from the National Aeronautics
and Space Administration (NASA), the Skaggs Institute for
Chemical Biology at The Scripps Research Institute, and through
a postdoctoral fellowship from the NASA Specialized Center
for Research and Training (NSCORT) in Exobiology.