J. evol.
Biol.
5: 173
3010-061X/92/02173
16 $ 1.50 +0.20/O
‘c> 1992 Birkhiuser
Verlag, Base1
188 (1992)
Mini-review
RNA in evolution:
Marie-Christine
Institut
France
a review
Maurel
Jacques Monad ~ CNRS,
Keq‘ irord.7: Origin
Tour 43, 2 place Jussieu,
of life; evolution;
RNA;
ribozyme;
75251 Paris Cedex OS,
editing.
Introduction
There are two main groups of molecules in the cell as it exists today: nucleic acids
which transmit genetic information
and participate directly in reproduction;
and
proteins which are responsible
for the metabolic functions
and chemical and
structural
relations within the cell.
What interests evolutionary
biochemistry
is how these first molecules came to
exist, their original replication and how the different classes of molecules relate to
one another.
What was the first system enabling information
to be transferred? Were the first
autoreplicative
molecules, the same as those we know today, or did they only have
certain similarities to our nucleic acids? How did relations between molecules come
about so as to construct the first metabolic pathways? Chemical reactions have to
be selective, rapid, therefore catalysed, to be efficient. Were the very first catalysts
which played a role in the first appearance of metabolism made up of enzymes such
as we know them today, i.e. complex and highly organised proteins? Or were they
quite simply mineral supports or reactive compounds?
From the point of view of molecular evolution i.e. before the appearance of cellular
life when prebiotic chemistry
furnished the basic building-blocks
of the living
organism we can suggest a number of hypotheses to answer these questions.
Today, of all known organic molecules, the nucleic acids alone are capable of
self-replication.
Thus, one of the key stages in the origin of life on earth was the
appearance of primitive molecules similar to nucleic acids.
1. The transfer
of information
and the first autoreplicative
molecules
The nucleic acids are made up of purines and pyrimidines, in which the nitrogen
base linked to sugar formed the nucleoside, which once it has been linked to a
173
174
Mallrel
phosphate, constitutes the nucleotide. The nucleotides are linked to one another by
a ribose-phosphate
backbone, and the strands thus created can be paired off head
to tail in a double helix maintained by specific hydrogen-bonds
that the bases set up
between them. When nucleic acids replicate, the two complementary
strands
separate, and then each of them regenerates the missing strand. In fact, each
nucleotide of a strand serves as a template and guides a complementary
subunit of
the growing chain. This is how information
is transmitted.
In the modern cell, this work is carried out by highly specialized enzymes:
gyrases, ligases, isomerases, polymerases etc. In primitive conditions however, both
synthesis and replication were achieved without the intervention of proteic enzymes.
The most plausible is non-enzymatic template-directed residue by residue replication. What is commonly referred to as template-directed synthesis has been carefully studied over the last twenty years in laboratory conditions, by Orgel and his
collaborators with the activated mononucleotides (Fig. la) (Orgel, L. E. 1987;
Zielinski W. and Orgel, L. E. 1987).
All these reactions take place with standard nucleotides on standard templates.
However, when we come to build the first autoreplicative molecule from start to
Fig. la. Template-directed
synthesis with
phosphate.
(From
L. E. Orgel, 1987).
a poly(C)
template
and an activated
derivative
of guanosine
5’
RNA in evolution: a review
Fig. lb. See text. (From Joyce, G. F. et al., 1987)
Fig. le.. See text. (From L. E. Orgel, 1987).
175
176
Maurel
finish and in the original conditions (Miller, S. L. 1955; Orgel, L. E. et Lohrmann,
R. 1974) we come up against a certain number of problems. One of this, is the
origin of the molecular fragments of nucleotides.
In the case of syntheses of the bases, it is easy to obtain purines, with the
evolution of HCN in water (Ferris, J. P. 1984) but only very little pyrimidines. In
nucleoside synthesis, no nucleoside can be detected if the base is a pyrimidine
( < 0.1%). When puric bases and ribose are heated equivalent nucleosides are
formed (Fuller, W. D. et al., 1972; Maurel, M. C. and Convert O., 1990). In the
case of sugar synthesis (Miyoshi.
E. et al. 1983) a complex and unstable mixture is
formed where ribose is not the major product. Finally, Joyce et al. (1987), have
shown that the template-directed
synthesis of an enantiomer is strongly inhibited by
the presence of the other enantiomer.
Therefore, contemporary
research is moving towards the search for polymers
simpler than the well-known
strands of RNA (Spach, G. 1984; Schwartz, A. W.
and Orgel, L. E. 1985).
Modzjication
of the Chose-phosphate
backbone
If an acyclic compound takes the place of the ribose, it is henceforth possible to
make simplified chains. The analogs proposed are acyclonucleosides
derived from
glycerol, acrolei’n and erythritol
(Fig. lb-c).
Here it is necessary to add that
acrolei’n can be easily obtained in supposedly prebiotic conditions and can also lead
to the synthesis of aminoacids judged to be important at the beginning of life on
earth. These are methionine, homocystei’ne, glutamate, homoserine,
a and #l diaminobutyrate.
Other changes which use nucleoside analogs and which enable new pairings to
take place are possible. They can facilitate the appearance of certain reactive groups
belonging to the bases, such as imidazole moiety of purine, which is now able to
exert a catalytic activity (Maurel, M. C. and Ninio, J. 1987; Maurel, M. C. 1988).
Wtichtershauser,
following earlier research of D. Rernal (1951), H. Hartmann
( 1974) and G. Cairns-Smith
(1982) suggests the existence of a primeval evolution
of polyanionic molecule fixed by ionic bonds to a mineral surface of pyrite (Fe&)
(Wachtershiuser,
G. 1988). Without going into the details of this theory, known as
surface metabolism,
let us see how Wdchtershduser
conceives the formation
of
nucleic acids.
No biosynthesis of the pyrimidines is possible, nor can the bases themselves make
ionic bonds. The formation
of purines however is possible under the following
conditions. A superficial organic network is formed by fixing the C of atmospheric
CO, and by taking advantage of the redox process of converting ferrous ions and
hydrogen sulfide into pyrite:
4 CO2 + 7 FeS + 7 H,S + (CH,COOH),
+ 7 FeS, + 4 H,O.
A sugar-phosphate
backbone will be formed thanks to phosphotrioses
produced
by this kind of reaction with the phosphates providing the bond with the surface.
RNA
in evolution:
177
a review
Fig. 2. All purine base-pairs.
a/N, bonded
guanine paired with N, bonded isoguanine.
adenine paired with
(From
WPchterhHuser,
N, bonded
G., 1988).
xanthine.
b/N,
bonded
Wlchtershiuser
calls this structure phosphotriboses
in order to stress their functional and biosynthetic relation to ribose. Once the phosphotriboses
have fixed the
imidazole ring by the formation of a Schiff base, the author proposes the construction of puric bases. This has the advantage of resembling the current biosynthetic
way where the purines are created with phosphoribosyl.
Wachtershguser’s
hypothesis is that of an all-purine precursor of nucleic acids (1988) (Fig. 2). The theory
briefly outlined here is supported by the supposed existence of molecular remains in
the present metabolism. Although complete and intellectually satisfying, it still lacks
its experimental trump-card.
2. Primitive
catalysts
and purines
In the list of modified nucleotides can be found all the functional groups of
aminoacids in proteins, with one exception: Imidazole. Now, imidazole is one of the
most important
reactive groups making up histidine, an aminoacid often represented in the active site of numerous proteins. Furthermore,
primitive nucleotides
were not necessarily limited to the standard nucleotides used today.
In our laboratory, we looked for imidazole among the prebiotic nucleosides and
this enabled us to show that N6-ribosyl
adenine (Fuller, W. D. et al., 1972) a
nucleoside which is easily formed in the plausible prebiotic conditions, is as active
178
Maurel
as histidine in the model reaction of hydrolysis of para-nitrophenylacetate
(Maurel,
M. C. and Ninio, J. 1987; Maurel, M. C. 1991). So, the presence of imidazole in the
nucleoside and in histidine (Fig. 3) puts us on the trail of the metabolic origin of
the aminoacid.
Indeed, histidine is, with arginine and lysine, one of those
aminoacids which are difficult to obtain in “classical”
prebiotic conditions.
It is
known, however, to be the only aminoacid whose cellular biosynthesis is initiated
by a purine (Fig. 4). A possible primordial
metabolic link between the two
compounds was thus pointed at very early. We are justified in considering that
catalytic groups, formerly made up of nucleic acids components, were incorporated
in the course of evolution into specific aminoacids and became specialized for a type
of catalysis. From this perspective White H. B. had already suggested as early as
1976 that the present coenzymes might be the fossils of nucleic enzymes (White H.
B., 1976).
On the basis of all these elements, I believe that the purines with their reactive
imidazole probably played a central role as catalytic precursors in primitive metabolism. It must be stressed that adenine is one of the most frequently found heterocyclic compounds in the world of modern biochemistry,
that purines are the easiest
compounds to be synthesized in experiments simulating prebiotic synthesis, and that
in modern metabolism, they are constituents
of both nucleic acids and numerous
coenzymes (for example: NAD, NADP, FAD, coenzyme A, coenzyme B 12.).
We can ask ourselves, therefore, why evolution should have prefered to opt for
protein catalysts rather than for nucleic acids. There is a number of possible reasons
for this. When the catalyzed reaction is a simple proton transfer, a reactive group
such as imidazole is sufficient to transform a substrate into a product (catalysts of
reduced specificity could participate in multiple reactions). But the growing complexity over the ages, called for specific catalysts to select the proper substrate,
which were obtained, by the conformation
of proteins. Moreover, the great number
of building-blocks
in proteins, allow them to have more functionalized
groups.
Finally the current modifications of the nucleotides are basically postranscriptional,
Fig. 3. See text.
(From
Maurel,
M.
C.
and Ninio,
J. 1987).
RNA
in evolution:
Fig. 4. Origin
179
a review
of the atomes
of histidine.
and it would probably cost to the modern cell too much effort to obtain catalysts
in this way.
In 1988, A. R. Hill and L. E. Orgel showed that a nucleotide analog, N3-Ribofuranosyladenine
5’P, which must be considered as a plausible constituent
of a
prebiotic monomer, polymerizes more rapidly and more effectively when faced with
a Poly U template than the standard nucleotide (Hill, A. R. et al., 1988). This
experiment leads us to conclude that any heterocycle could replace the purines and
pyrimidines. In fact, stacking one on top of the other the pairs of molecules able to
form between them pairings through weak bonds would be sufficient to support an
information
transfer system. This lead us logically to ask what is the smallest
biological unit capable of self-replication
according to these rules.
The nitrogen bases can pair, and in this case, the fundamental question is now
that of the synthesis of the nucleoside or its analog capable of linking up with
several elementary heterocyclic units with a common backbone.
The oligomers of N3-Ribofuranosyladenine
5’P, (personal gift from L. E. Orgel),
show no catalytic activity (unpublished
results) for the pairings produced by
nitrogen in position 7, block the proton relay properties of imidazole.
It would be particularly interesting to test the first purine-purine
hypothesis that
we mentioned above (Fig. 2). As can be seen from the figure, the imidazole is in this
180
Maurel
case completely free and available for catalysis. Moreover, N3-Ribosyl
xanthine, is
known to exist in procaryotic
and eucaryotic cells (Hatfield, D. and Wyngaarden,
J. B. 1964) and has no known function today. However,
this puric nucleotide
biosynthesis
is interesting thanks to an uridine pyrophosphorylase,
a pyrimidine
enzyme. Is this a left-over from purine-pyrimidine?
The practical problem facing us today is that of studying the catalytic activity of
nucleic acids containing prebiotic elements. One possible way of investigating this
type of catalyst is to synthesise polymers already containing nucleotides possessing
catalytic groups. To this end, we are working with Jean-Luc D&out (L.E.D.S.S.
6-Grenoble-France),
to increase the catalytic effect of N6 ribosyl adenine. The
adenine rings could be attached to a polymeric chain thanks to a reaction of
6-chloropurine
with a polyamine such as polylysine.
Within the field opened up by studying catalysis by nucleic acids, C. Switzer et al.
(1989), have shown an enzymatic incorporation
of new functionalized
bases into
RNA and DNA. This expanded the genetic alphabet from 4 to 6 letters, permits
new base pairs, and provides RNA molecules with the potential for greatly
increased catalytic power.
3. Why RNA?
The fundamental reason is the ability of RNA to store genetic information,
to
self-replicate, and to promote catalytic activity. That RNA preexists to DNA is
plausible on account of the following
observations,
many of which have been
already compiled by many authors (A. Lazcano et al., 1988; A. Lamond and T.
Gibson,
1990). The synthesis of the deoxyribonucleotides
are a reduction of
ribonucleotides
which therefore precede them. This reaction involves an enzyme,
the ribonucleoside
phosphate reductase, which as a protein has been perfectly
conserved. Thymine, the specific base of DNA, is obtained by methylation
of
uracile which is specific to RNA. Moreover,
we know that protein synthesis can
take place without DNA, but never without RNA. We also know that RNAs are
primers for DNA synthesis with some DNA polymerase, whereas RNA synthesis
with RNA polymerases takes place without a primer.
In fact, DNA is now considered to be an RNA modified in favor of a greater
chemical stability, due essentially to the absence of the 2’ OH of ribose. This
stability enables DNA to stock and preserve efficiently all genetic information.
If we draw up a list of all the biological functions performed by RNA molecules
in cellular processes, we find RNA to be involved in for example, mRNA, rRNA,
and tRNA, Ul to Ull sn RNA, in Telomerase RNA (Company,
M. et al., 1991;
Schwer, B. and Guthrie, C. 1991). RNA participates in the biosynthesis
of chlorophyll (Kannangara,
C. G. et al. 1988) and is involved in the branching reaction of
polysaccharides
(Petrova, A. N. and Filippova, R. D. 1971). RNA is the genetic
material of some viruses and phages and is constitued by four nucleotides selected
to be useful in polysaccharide
synthesis (UDP), in lipid synthesis (CDP), in protein
synthesis (GTP). It also brings energy with ATP etc. Moreover,
if the recent
RNA
in evolution:
181
a review
discovery of editing processes is taken into account, along with the even more
spectacular discovery of the catalytic properties of RNA, and the omnipresence of
puric and pyrimidic ribonucleotidic
coenzymes, then we must accept the idea put
forward a long time ago (Orgel, L. E. 1968 and Crick, F. 1968), according to which
RNA or related molecules played a fundamental role in primitive evolution.
All these results, can lead us to imagine an RNA world as a necessary stage in
evolution (Gilbert, W. 1986), and an early RNA genome organization leading to
cell evolution (Darnell, J. E. and Doolittle, W. F. 1986). It has been suggested that
some RNA viruses (such as turnip yellow mosaic virus and bacteriophage QP),
which have structures at the 3’ termini of their genomes that resemble tRNAs are
in fact molecular fossils and that this tRNA-like
structure
is indicative of an
evolutionary
link between replication and translation (Weiner, A. M. and Maizels,
N. 1987). Others postulate primeval metabolic riboorganism
breakthrough
(Benner,
S. A. et al, 1987).
4. RNA catalysis
in primitive
evolution and RNA today
If the earliest genes were made of RNA, it is possible that RNA-catalysed
of rRNA
of
cleavage and ligation is a very old process. In the self-splicing
Tetrahymena
thermophila,
(see section on ribozymes
below),
the required
guanosine, where both 2’ and 3’ hydroxyls are essential to break the phosphodiester
bond (Bass, B. L. and Cech, T. R. 1984), and the required guanosine rich-sequence
within the intron, are again more suggestive of the ubiquity of purines. In fact, the
catalytic activity of ribonucleic acids has been known for more than twenty years in
the catalysis of the glycyl-glycine synthesis by poly(U), the acetyl group transfer
reactions from one nucleoside to another, and the hydrolysis of 2’-5’ linked oligo
(A)s in the presence of poly(U) (Weber, A. L. and Orgel, L. E. 1980; Chung, N.
M. et al., 1971; Usher, D. A. and McHale A. H., 1976). More recently, Cech et al.
( 1981) showed that the ribosomal RNA of a Tetrahymena thermophila protozoan,
is capable of self-splicing without proteic enzyme.
a) The ribozJ!mes or catalytic RNA
The eucaryotic genes are known to comprise coding sequencescalled exons (for
expressed sequences), interrupted by long non-coding sequences, the introns (or
intervening sequences: 1%). The transcriptional products are not therefore functional at once. The RNA messengerundergoes a series of enzymatic changes which
lead to the elimination of the introns and the joining together of the exons. For a
long time, it was believed that only the eucaryotic genes were interrupted by the
introns, but the discovery of introns, firstly in archaea (Kjems, J. and Garret, R. A.,
1985). then in the cyanobacteria (Ming-Qun Xu et al., 1991; Kushel et al., 1991),
favors the view that introns are very ancient. Furthermore, the homology of
sequencesof the introns in chloroplasts and cyanobacteria, is a strong evidence for
182
Table
Maurel
1. Different
kinds
of RNA
processing
reaction
Mechanism
I. Group
2. Group
3. Nuclear
I intron
11 intron
pre-mRNA
self-splicing
self-splicing
splicing
4. Self-cleavage
of plant viroi’ds,
virusoYds and linear satellite
RNAs
5. Pre-tRNA
Excgenous
guanosine
. Transesterification
l
I-
* Endogenous
adenosine
* Transesteritication
Lariat
l
l
Transphosphorylation
- Cleavage
by RNase P of
the 5’-precursor
specific
sequence
Ckcurence
* Nuclear
rRNA
genes
Mitochondrial
mRNA
and rRNA
genes
* Chloroplast
tRNA
genes
l
l
Structural
genes of fungal
and plant mitochondrial
DNA structural
and
tRNA
genes of chloroplasts
* RNA of virus,
and virusoi’ds
viro’ids
* tRNA
phylogenetic
continuity
and implies that they were present in their common
ancestor which is probably 3.5 billion years old, because this is the age of the first
cyanobacteria
microfossils
(Schopf, J. and Packer, B. M. 1987).
The splicing of exons in a large number of organisms has been studied in detail.
This splicing can take place in different ways according to the kinds of introns,
which are themselves divided into two groups (Table 1: the different kinds of
RNA-processing
reactions). When the RNA catalyses its own splicing, its activity is
said to take place in cis. If the RNA catalyses the splicing of other RNA molecules,
the ribozyme is said to take place in trans. When the RNA loses its 3D structure,
it loses its capacity for self-splicing.
How was this actiaity brought to light?
In 1981, Cech et al. were studying the splicing of ribosomal RNA of a ciliated
protozoan
Tetrahymena
thermophila.
They followed the splicing reaction when
nucleic extracts (nucleics acids + proteins),
magnesium and nucleoside triphosphates were present. They noticed that the reaction took place without
nucleic
extracts. Two hypotheses were possible: either the catalytic proteins are strongly
bound to the RNA, or the RNA catalyses its own maturation.
This was shown
when the ribosomal gene, cloned in E. coli, purified, then transcribed into E. coli,
is capable of self-splicing without the presence of enzymes, since it has never entered
into contact with the Tetrahymena enzymes.
What is the chemical mechanism of the reaction? (Bass, B. L. and Cech, T. R.,
1984; Zaug, A. J. and Cech, T. R., 1986; Peebles, C. L. et al., 1986).
Without going into the details, (see references) we must know that the introns
seem to be divided into two main categories (Michel, F. et al., 1982). The introns
RNA
in evolution:
a review
183
of group I follow the same pattern as the Tetrahymena thermophila intron. Among
them we find the mRNA(s)
of Neurospora
Crassa, mRNA and RNA of yeast,
certain plant mitochondrial
RNAs and alga chloroplast RNA as well as bacteriophage T4. The introns of group 11 follow a different pattern. These are the introns
of certain mitochondrial
genes found in funghi and chloroplastic
genes in Euglena
and higher plants. An RNA enzyme, like a protein enzyme, requires a specific
structure for its biochemical activity. Splicing reactions are reversible, which means
that introns can be integrated into RNA, and possible implications are to be seen
in the case of mobile introns and retroelements.
Conditions exist where the intron can have a catalytic effect in trans, in other
words, on other RNA. The catalytic activity of RNase P, the maturation enzyme of
the tRNA, was isolated by Guerrier-Takada,
C. and col., (1983). They proved that
enzymatic activity depended solely on the RNA fragment linked to a protein. The
RNA isolated in-vitro is able to cut the precursor of the tRNA and has therefore
all the features of a ribozyme.
The self-hydrolysis
of viroi’ds is also known (Buzayan, J. M. et al., 1986; Forster,
A. C. and Symons. R. H. 1987; Uhlenbeck, 0. C. 1987). Many RNA viruses have
a ribozyme activity which occurs during viral multiplication.
Certain of these
viruses replicate by using the “rolling circle” mechanism. An analysis of the areas
concerned by the self-catalytic cuts brings to light a common structure of some 30
nucleotides; this is called a hammerhead structure. This hammerhead presents a
particular secondary structure in the form of a T with several specific couplings
(Rutfner,
D. E. et al., 1989; Fedor, M. and Uhlenbeck, 0. C. 1990). Due to these
different discoveries artificial ribozymes are synthesized (Koizumi,
M., 1988).
Another catalytic activity isolated could (if confirmed) widen the reactional field
of RNA, which could thus influence other kinds of molecules. It is the a-l-4 D
glucotransferase
or branching enzyme which carries out the transfer of glycosyl
residues. The enzyme is in two parts, one proteic, the other nucleotidic. The
nucleotidic part is an RNA of 31 nucleotides, ten of which are modified nucleotides
and this part alone is active in the transfer reaction (Schvedova, T. A. et al., 1987).
To sum up, here are the main catalysed reactions already listed for the ribozyme:
ribonuclease, phosphotransferase,
phosphatase, ligase, sequence specific endonuclease, nucleotidyl transferase, glucotransferase
activity. Moreover, a modified version
of the Tetrahymena ribozyme, can be made to act like a replicase, thus demonstrating the feasibility of template-directed
RNA-catalysed
RNA replication (Doudna,
J. A. and Szostak, J. W. 1989).
b) Editing
The meaning of a genetic message can be transformed
in the course of its
expression.
It is even possible for new information
originally inexistent in the
genome to be created. In this case we are faced with a rewriting
of the genetic
message. Up to now, the revision of RNA is mostly observed in mitochondrial
RNAs of the kinetoplastid
protozoa, moulds, paramyxovirus
or plants.
184
Maurel
RNA editing is a postranscriptional
process by which the primary structure of an
RNA is altered by nucleotide insertions, deletions or alterations (Stuart, K. et al.,
1989; Benne. R. 1990). Any difference therefore between what are known as the
primary products of transcription
and the functional RNA can be often important.
For example, RNA editing lies in the addition or suppression
of uridine, in a
position internal to the mRNA. The addition of U can be made at any point of the
RNA, this opens new AUG initiation codons or has an effect on the coding areas,
or modifies the sequence up to the limit of 50%. New reading frames and/or new
codon stops are created. There are also the C-U
conversions
in some plant
mitochondria
(Gualberto,
J. M. et al., 1989), and an extensive cytidine insertion in
the mitochondrial
RNA of Physarum polycephalum (Mahendran,
R. et al. 1991).
One of the most striking cases of editing has been described in the case of
trypanosome:
the messenger of the subunit-III
of the cytochrome oxydase (Feagin,
J. E. et al., 1988). The gene for this protein was already known and analysed in the
case of two neighbouring
species, but the search for a homologous
gene in
Trypanosoma
Brucei’ failed. In fact, the RNA was identified, but the corresponding
gene could not be found. It was conjectured that the messenger had been the object
of substantial editing. The next step was then to look in DNA for sites of homology
with a given message. A comparison between the DNA and the RNA now revealed
the addition of 347 uridines in 121 different sites. This represents 55% of the
nucleotides of the messenger that are not present in the gene. L. Simpson ( 1989) has
called the incomplete genes, cryptogenes.
does the editing process take place?
Primary RNA transcripts and non-modified, RNA partially modified in the 3’
side but not on the 5’ side, can be found. This indicates the direction of the revision.
It is thought likely that an editosome complex interacts with the RNA by becoming
fixed to the sequences at the 3’ end, thus making the first modifications. This
complex then shifts towards the 5’ end carrying out modifications all the time.
Certain portions, for example, undergo successive additions of uridine and this
transforms the molecule which now assumesthe property of a substrate for the
following revisions. These successiveadditions show that certain sites of recognition
can be cryptic in the primary transcription products and do not apppear until
changes in the substrate have taken place. The structure and composition of the
regions targetted by the editosome are still not well understood. But they are known
to be often very rich in G. These editosomes are capable of a whole range of
activities; an RNase activity followed by insertion of uridine and then ligation of
the modified RNA. Surplus uridines are often added, some of which must therefore
be eliminated before closing the molecule. We are therefore dealing with a large
complex made up of a 3’ terminaluridyltransferase (a TUTase), a ribonuclease, an
exonuclease and a ligase (Simpson, L. and Shaw, J. 1989). The riboendonuclease
makes a cut within the pre-edited sequence at specific sites. TUTase allows the
addition of U at the points where the sites are cut. The exonuclease removes the
excess of U and the ligase closes the cut by joining the two strands. Up to now it
has been possible to isolate TUTase and ligase. Recently, in the case of the
Hw
RNA
in evolution:
a review
185
mitochondrion
of Leishmania Tarentolae, Blum, B. et al. (1990), have shown
“guide RNA” molecules (gRNAs)
which encode the information
for RNA editing.
Volloch, V. et al. (1990) proposed a template-directed
editing process, a de now
synthesis of edited mRNA.
Other correcting mechanisms exist: for example, some changes could be due to a
sort of “stuttering”
of the RNA polymerase (double insertion of G in SVSP:
Thomas, S. M. et al. 1988). The mRNA apolipoprotein
B in mammals undergoes
changes at limited points. C is changed to U by enzymatic deamination: this makes
a transition from CAA to UAA and generates a termination codon (Higuchi, K. et
al. 1988). All these examples illustrate the considerable flexibility of the genetic
material and can be interpreted as processes of adaptation or vestiges of primitive
processes that the system of genetic expression must have been subjected to in the
course of evolution. The fact that the editing process is widespread in mitochondria
seems to indicate that it existed in the procaryotic
ancestors from which they
derived.
However, as we have seen, there exist different forms of revision of RNA which
do not stem from the same historical process. Thus the chemical change in a
template nucleotide demands a complex enzymatic machinery and is quite different
from the insertion-deletion
of a nucleotide. The same can be said for the stuttering
of a polymerase whose functionning
is quite different from that of an editosome.
We have already seen that the first RNAs were probably made up entirely of
purines. The editing that consists of C/U insertion can be a method for adding
pyrimidines.
At the earliest stage of the metabolism the RNA revision may well
have functioned to incorporate a second class of nucleotides (pyrimidines)
into a
pre-existing RNA.
In those organisms,
that are capable of editing today, there exists a greater
genetic flexibility. The editing can be used to control genetic expression. With the
trypanosoma,
it has been observed that the edition of certain messengers can take
place only at certain phases in the life of the parasite, whereas others do so
permanently
and therefore depend on a regulation determined
by an as yet
unknown demand. Couldn’t this be a key to the processes of adaptation?
In fact it would appear that evolution can advance more rapidly at the level
of RNA than DNA and that, moreover, is less dangerous for the organism.
Indeed an error in editing can easily be corrected, whereas a mutation in DNA can
be fatal.
The editing process would therefore seem to be the opposite of splicing. In the
latter case there is a phenomenon of condensation
(by the elimination of the
introns) of genetic information,
whereas when RNA is revised, nucleotides are
added, and functional molecules are longer than the primary transcripts.
(See also
Cech, T., 1991). Another conclusion is that the splicing process allows the organism
to gain space by making the genome more compact. The technology of cells to-day
consists in unwiding, then cutting up the message, and then sticking the different
elements together so as to decode. In this way, it is possible to stick together
different pieces of the genome, to create novel activities. RNA self-splicing can be
considered to be the first form of genetic recombination.
186
Maurel
Turning to the origin of life now, we can say that it would be a gradual process
rather than a singular event and progressed through a braided network of alternatives routes. Accordingly, we must interpret the versatility of RNA.
Acknowledgements
I thank Dr. Ninio
talented figures.
for
his helpful
comments
of the manuscript
and
Martine
Dombrosky
for
her
References
Bass, B. L. and Cech, T. R. 1984. Specific interaction
between the self-splicing
RNA of Tetrahymena
and
its guanosine
substrate:
implications
for biological
catalysis by RNA. Nature
308: 820-826.
Benne, R. 1990. RNA editing in trypanosomes:
is there a message? T.1.G 6: 177-181.
Benner,
S. A., Alleman,
R. K., Ellington,
A. D., Ge, L.. Glasfeld,
A., Ieanz,
G. F., Krauch,
T.,
MacPherson,
L. J., Moroney.
S., Picirilli,
J. A. and Weinhold
E. 1987. Natural
selection,
protein
engineering,
and the last riboorganism:
rational
model building
in biochemistry
Cold. Spring.
Harbor.
Symp.
Quant. Biol. Vol LIT. 53363.
Bernal, J. D. 1951. The physical basis of life. Routledge
and Kegan Paul. London.
Blum, B., Bakalara,
N. and Simpson,
L. 1990. A model for RNA editing in kinetoplastid
mitochondria:
“guide”
RNA molecules
transcribed
from maxicircle
DNA provide
the edited information.
Cell.
60: 189 198.
Buzayan,
J. M., Gerlach,
W. and Bruening,
G. 1986. Non enzymatic
cleavage and ligation
of RNAs
complementary
to a plant virus satellite RNA.
Nature.
323: 3499353.
Cairns-Smith,
A. G. 1982. Genetic takeover
and the mineral origin of life. Cambridge
University
Press.
Cambridge,
Great-Britain.
Cech, T. R. 1991. RNA editing: World’s
smallest introns? Cell. 64: 667 669.
Cech, T. R., Zaug, A. J. and Grabowsky,
P. J. 1981. In vitro splicing of the ribosomal
RNA precursor
of Tetrahymena:
involving
of a guanosine
nucleotide
in the excision of the intervening
sequence.
Cell. 27: 487-496.
Chung,
N. M., Lohrmann,
R. and Orgel, L. E. 1971. Template
catalysis
of acetyl transfer
reactions,
Biochim.
Biophys.
Acta. 228: 5366543.
Company,
M., Arenas, J. and Abelson,
J. 1991. Requirement
of the RNA helicase-like
protein
PRP22
for release of messenger RNA from spliceosomes.
Nature.
349: 487-493.
Crick, F. 1968. The origin of the genetic code. J. Mol. Biol. 38: 367-369.
Darnell,
J. E. and Doolittle,
W. F. 1986. Speculations
on the early course of evolution.
Proc. Natl. Acad.
Sci. USA. 83: 1271-1275.
Doudna,
J. A. and Szostak,
J. W. 1989. RNA
catalysed
synthesis
of complementary-strand
RNA.
Nature.
339: 5199522.
Feagin, J. E., Abraham,
J. M. and Stuart, K. 1988. Extensive
editing of the cytochrome
c oxydase III
transcript
in Trypanosoma
brucei. Cell. 53: 413-422.
Fedor,
M. J. and Uhlenbeck,
0. 1990. Substrate
sequence effects on hammerhead
RNA
catalytic
efficiency.
Proc. Natl. Acad. Sci. USA. 87: 166881672.
Ferris, J. P. 1984. The chemistry
of life’s origin. Chem. Eng. News. 62: 22-35.
Ferris, J. P. 1987. Prebiotic
synthesis: problems
and challenges.
Cold Spring Harb. Symp. Quant. Biol.
52: 29935.
Forster,
A. C. and Symons,
R. H. 1987. Self-cleavage
of plus and minus RNAs of a virusoid
and a
structural
model for the active sites. Cell 49: 211-220.
RNA
Fuller,
in evolution:
a review
187
W. D., Sanchez, R. A. and Orgel, L. E. 1972. Studies in prebiotic
synthesis
Vl. Synthesis of
put-me nucleosides.
J. Mol. Biol. 67: 25-33.
Gilbert,
W. 1986. The RNA world. Nature.
319: 618.
Gualberto,
J. M., Lamattina,
L., Bonnard,
G., Weil, J. H. and Grienenberger,
J. M. 1989. RNA editing
in wheat mitochondria
results in the conservation
of protein sequences. Nature.
341: 660 662.
Guerrier-Takada,
C., Gardincr,
K., Marsh,
T., Pace, N. and Altman,
S. 1983. The RNA moiety of
ribonuclease
P is the catalytic
subunit of the enzyme.
Cell. 35: 8499857.
Hartman,
H. 1975. Speculations
on the origin and evolution
of metabolism.
J. Mol. Evol. 4: 359 370.
Hatfield,
D. and Wyngaarden,
J. B. 1964. 3-Ribosylpurines,
J. Bol. Chem. 239: 2580-2592.
Higuchi,
K., Hospattankar,
A. V.. Law, S. W., Meglin.
N., Cortright,
J., and Brewer,
B., Jr. 1988.
Human apolipoprotein
B mRNA:
identification
of two distinct apoB mRNAs,
an mRNA
with the
apoB-I00
sequence
and an apoB mRNA
containing
a premature
in frame translational
stop
condon,
in both liver and intestine.
Proc. Natl. Acad. Sci. USA. 85: 1772- 1776.
Hill, A. R., Kumar,
S., Leonard.
N. J. and Orgel, L. E. 1988. Template-directed
oligomerization
of
3-isoadenosine
S’phosphate.
J. Mol. Evol. 27: 91-95.
Joyce, G. F., Schwartz,
A. W., Miller,
S. L. and Orgel, L. E. 1987. The case for an ancestral
genetic
system involving
simple analogoues
of the nucleotides.
Proc. Natl. Acad. Sci. USA. 84: 4398-4402.
Kannangara,
C. G., Cough,
S. P., Bruyant,
P., Hoober,
J. K., Kahn, A., Von Wettstein,
D. 1988. tRNA
Glu as a cofactor
in d-aminolevulinate
biosynthesis:
steps that regulate
chlorophyll
synthesis,
TIBS. 13: 139 143.
Kjems, J. and Garrett,
R.A: 1985. An intron in the 23s ribosomal
RNA gene of the archaebacterium
Desulfurococcus
mobilis. Nature.
318: 675 677.
Koizumi.
M., Iwai, S. and Ohtsuka,
E. 1988. Cleavage of specific sites of RNA designed ribozymes.
Febs
Letters. 239: 285 -288.
Kuhsel, M. G., Strickland,
R., and Palmer, J. D. 1991. An ancient group I intron shared by eubacteria
and chloroplasts.
Science. 250: 1570- 1573.
Lamond,
A., and Gibson,
T. 1990. Catalytic
RNA and the origin of genetic systems, TIC. 6: l45- 149.
Lazcano,
A., Guerrero,
R., Margulis,
L. and Oro, J. 1988. The evolutionary
transition
from RNA to
DNA in early cells. J. Mol. Evol. 27: 2833290.
Mahendran,
R., Spottswood,
M. R. and Miller,
D. L. 1991. RNA
editing by cytidine
insertion
in
mitochondria
of Physarum
polycephalum.
Nature.
349: 434-438.
Maurel,
M. C. and Ninio, J. 1987. Catalysis by a prcbiotic
nucleotide
analog of histidine.
Biochimie.
69:
551-553.
Maurel,
M. C. 1988. Acides Nucleiques:
Origines et activites.
C.R. Exobiologie
C.N.E.S.
edit& par F.
Raulin et A. Brack. 47752.
Maurel,
M. C. and Convert,
0. 1990. Chemical
structure
of a prebiotic
analog of adenosine.
Origins of
Life. 20: 43-48.
Maurel,
M. C. 1991. Primitive
evolution:
early information
transfer
and catalysis
by purines. Lecture
Notes in Physics. in press.
Michel,
F., Jacquier,
A., Dujon, B. 1982. Comparison
of fungal mitochondrial
introns reveal extensive
homologies
in RNA .sccondary structure.
Biochimie.
64: 867-881.
Miller,
S. L. 1955. Production
of some organic compounds
under possible primitive
earth conditions.
J.
Am. Chem. Sot. 77: 2351-2361.
Ming-Qun
Xu, Kathe,
S. D., Goodrich-Blair,
H., Nierwicki-Bauer,
S. A. and Shub, D. A. 1991.
Bacterial Origin of a chloroplast
intron: Conserved
self-splicing
group I introns in cyanobacteria.
Science, 250: 1566- 1570.
Miyoshi,
E., Kobayashi,
A., Yanagisawa,
S. and Shirai, T. 1983. Studies on formose sugars formed by
wet discharge or ultraviolet
irradiation.
The Chemical
Society of Japan, 10, 1449- 1455.
Orgel, L. E. 1968. Evolution
of the genetic apparatus.
J. Mol. Biol. 38: 381-393.
Orgel, L. E. 1986. RNA catalysis and the origins of life. J. Theor. Biol. 123: 127- 149.
Orgel, L. E. 1987. Evolution
of the genetic apparatus:
a review. Cold. Spring. Harb. Symp. Quant. Biol.
52: 9-16.
188
Orgel,
Maurel
L. E. and Lorhman,
R. 1974. Prebiotic
chemistry
and nucleic acid replication
Act. Chem. Res.
7: 368 377.
Peebles, C. L., Pcrlman,
P. S., Meckenlenburg,
K. L., Petrillo,
M. L., Tabor, J. H., Jarrell, K. A. and
Cheng, H. L. 1986. A self splicing RNA excise an intron lariat. Cell. 44: 213 -223.
Petrova,
A. N. and Filippova,
R. D. 1971. On the participation
of low polymeric
ribonucleic
acid in the
branching
reaction
of polysaccharides.
Enzymologia.
40: 127 139.
Picirilli,
J. A., Krauch,
T.. Moroney,
S. E. and Benner. S. A. 1990. Enzymatic
incorporation
of a new
base pair into DNA and RNA extends the genetic alphabet.
Nature.
343: 33-37.
Ruffner,
D. E., Dahm. S. C. and Ulhenbeck,
0. C. 1989. Studies on the hammerhead
RNA self-cleaving
domain.
Gene. 82: 1: 31-41.
Schopf, J. W. and Packer, B. M. 1987. Early archaen (3,3-billion
to 3,5-billion-year-old)
microfossils
from warrawoona
group, Australia.
Science. 237: 70-73.
Schwartz,
A. W. and Orgel, L. E. 1985. Template-directed
synthesis of novel, nucleic acid-like structures.
Science. 228: 5855587.
Schwer, B. and Guthrie,
C. 1991. PRPI 6 is an RNA-dependant
ATPase that interacts transiently
with
the spliceosome.
Nature.
49: 494 -499.
Shvedova,
T. A.. Korneeva,
G. A., Otroshchebko,
V. A. and Venkstern,
T. V. 1987. Catalytic
activity
of the nucleic acid component
of the l-4 a glucan branching
enzyme from rabbit muscles. Nucleic
Acids Research.
15: 1745- 1751.
Simpson,
L. and Shaw, J. 1989. RNA
editing
and the mitochondrial
cryptogenes
of kinetoplastid
protozoa.
Cell. 57: 355 366.
Spach, G. 1984. Chiral
versus chemical
evolutions
and the appearance
of life. Origins
of Life. 14:
433 437.
Stuart, K., Feagin J. E. and Abraham,
J. M. 1989. RNA editing: the creation
of nucleotide
sequences
in mRNA
a minireview.
Gene. 82: 1555160.
Switzer.
C., Moroney,
S. E. and Benner, S. A. 1989. Enzymatic
incorporation
of a new base pair into
DNA and RNA. J. Am. Chem. Sot. I I I: 8322 8323.
Thomas,
S. M. 1988. Two mRNAs
that differ by two no-templated
nucleotides
encode the amino
coterminal
proteins
P and V of the paramyxovirus
SVSP. Cell. 54: 891-902.
Uhlenbeck,
0. C. 1987. A small catalytic
oligoribonucleotide.
Nature.
328: 596.
Usher. D. A. and McHale,
A. H. 1976. Hydrolytic
stability
of helical RNA: a selective, advantage
for
the natural 3’, S’, bond. Proc. Nat]. Acad. Sci. 73: 114991153.
Volloch,
V., Schweitzer,
B. and Rits. S. 1990. Uncoupling
of the synthesis of edited and unedited CO111
RNA in Trypanosoma
brucei. Nature.
343: 482-484.
Wachtershauser,
G 1988. Before enzymes and templates:
Theory of surface metabolism.
Microbiological
Reviews.
52: 4522484.
Wachtershauser,
G. 1988. An all-purine
precursor
of nucleic acids. Proc. Nat]. Acad. Sci. USA. 85:
1134 1135.
Weber, A. L. and Orgel, L. E. 1980. Poly( U)-directed
peptide-bond
formation
from the 2’(3’)glycyl
esters of adcnosine derivatives.
J. Mol. Evol. 165: I-10.
Weiner,
A. M. and Maizels,
N. 1987. tRNA-like
structures
tag the 3’ends of genomic
RNA molecules
for replication:
implications
for the origin of protein
synthesis.
Proc. Nat] Acad. Sci. USA. 84:
7383 7387.
White, H. B. 1976. Coenzymes
as fossils of an earlier metabolic
state Mol. Evol. 7: 101~104.
Zaug, A. J. and Cech. T. R. 1986. The intervening
sequcncc of Tetrahymena
is an enzyme. Science. 231:
470 475.
Zielinski,
W. and Orgel, L. E. 1987. Autocatalytic
synthesis of a tetranucleotide
analogue.
Nature.
327:
346-347.
Received
18 July 1991;
accepted 9 August
199 I.
Corresponding
Editor: G. Wagner