Prebiotic evolution and the RNA World -...
Transcript of Prebiotic evolution and the RNA World -...
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XVII International Conference of the European Centre
for Science, Arts and Culture
Prebiotic evolution and the RNA World
Antonio LAZCANO
Miembro de El Colegio Nacional
Universidad Nacional Autónoma de México
Veli Losinj 2017
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Oparin’s step-wise heterotrophic origin of life
reducing atmosphere
synthesis of organic compounds
& formation of the primitive soup
coacervates
primordial heterotrophs
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Oparin’s heterotrophic scheme
1. set the question of the origin of life within a Darwinian
framework;
2. proposed a multi- and interdisciplinary research program;
3. reinterpreted many isolated chemical facts & observations
within an evolutionary sequence leading to the first organisms;
4. separated the idea of spontaneous generation of organisms
from the chemical and biochemical origins of life; and
5. based on pre-Mendelian genetics, he rejected the idea of a
“living compound” and suggested life as a property of systems
of molecules.
cf. Lazcano (2016) J Mol Evol 83: 214
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The 1953 Miller experiment
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Parker, Cleaves, Dworkin, Glavin, Audrey, Lazcano & Bada 2011
Amino acid abundances in the Murchison meteorite (blue) and in
prebiotic synthesis from CH4, CO2, NH3, H2O & H2S (black)
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The harvest of ‘53
Watson & Crick and the DNA double
helix model
S. L. Miller and the prebiotic
synthesis of amino acids
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Molecular biology and the origins of life:
the prebiotic synthesis of adenine
Oró, 1960; Ferris & Orgel, 1966
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Lazcano, Miller & Oró,1990
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Chromatogram of NH4CN polymerization at 80 °C
Borquez, Cleaves, Lazcano & Miller (2005) Origins Life Evol. Biosph. 35:79
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Borquez, Cleaves, Lazcano & Miller (2003) Origins Life Evol. Biosph. 35: 79
2,6 diaminopurine base pairs with uracil
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Rios & Tor (2013)
Nucleobases of abiotic origin. Red, in prebiotic simulations;
black, meteorites and prebiotic simulations
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Rios & Tor (2013)
Nucleobases of abiotic origin. Red, in prebiotic simulations;
black, meteorites and prebiotic simulations
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CO2, CO, N2, H2S, H2O, CH4
CO2, NH3, H2S, H2O
amino acids, nucleobases, sugars, lipids,
oligomers of biochemical compounds
Lazcano (2006)
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Szostak 2009
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HCN
Fe(CN)64-
CN-Fe2+, Mg2+, Ca2+, Na+, K+,
Based on Szostak (2017) & Lazcano (2006)
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Bracher 2015
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Miller-Urey one pot laboratory
simulations
syntheses of amino acids, hydroxyacids,
purines, sugars, etc
Production of a single class of biomolecule at
the time (mostly)
Low yields of some additional compounds
Formation of intractably complex mixtures of
organic compounds
System chemistry experimental
approach
Multi-pot experimental model of simultaneusly
interactive chemical subsystems
Involvement of non-prebiotic reactants
Requires high concentrations of H2S which
appear to be unlikely. The same would be true
for Cu, since in the primitive environment
Fe>Mn, Ni, Co >> Cd, Zn, Cu
Two opposing (?) ways of simulating prebiotic chemistry
syntheses of precurors of ribonucleotides,
amino acids, and lipids linked through
cyanosulfidic chemistry
Lazcano 2017
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Abiotic polymerization processes
Mineral & organic compound complexes
Formation of micelles & liposomes from
prebiotic lipidic molecules
The prebiotic soup
Coupling of catalytic chemical species with
replicative processes
Replicative systems capable of generating
adaptative complexity
cf. Lazcano 2017
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Abiotic polymerization processes
Mineral & organic compound complexes
Formation of micelles & liposomes from
prebiotic lipidic molecules
The prebiotic soup
Coupling of catalytic chemical species with
replicative processes
Replicative systems capable of generating
adaptative complexity
cf. Lazcano 2017
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Coupling of catalytic chemical species with
replicative processes
Replicative systems capable of generating
adaptative complexity
cf. Lazcano 2017
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DNA
DNA RNA protein
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DNA
DNA RNA protein
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RNA is a nucleic acid with a RIBOSE-
PHOSPHATE backbone
-ose is for sugars, and RIB for the
Rockefeller Institute of Biochemistry
What’s in a name?
Ettienne-Decant, J. (1988) Genetic Biochemistry: from gene to protein (Ellis Horwood Ltd)
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By the late 1950s, many were convinced that
since
a) viruses can be crystalized, it was argued that
they may be at the threshold of life; and
b) some viruses, like the tobacco mosaic virus,
have RNA genomes, therefore
…RNA genomes must be primitive!
A broken watch gives the right time now and then…
cf. Lazcano (2012) Hist.Phil.Life Sci. 34: 407
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The RNA Tie Club
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Neidhart, Ingraham & Schaechter (1990)
RNA is the second most abundant cell component
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“…There is no doubt that nucleic acids played an important role
in the evolution of the organic world and metabolic reactions.
Yet both RNA and DNA could hardly arise simultaneously in the
early evolution of life. It rather seems that ribonucleotides, and
then RNA, originated first. DNA came into existence far more
recently, as the protoplasm became more differentiated and its
functions grew in complexity.
“It seems that RNA, being associated with the most general
processes of life, was formed at an earlier evolutionary stage,
while the origin of DNA was associated with the development of
more specialized and phylogenetically later features of
organisms”
A.N. Belozersky, 1957 (1959)
Evolutionary biochemistry
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Evolutionary biochemistry:Ribonucletidyl coenzymes as remnants of an early
stage of metabolism*
Benner et al. 2010
* Handler (1961), Eakin (1963), Orgel (1968, 1971) & White III (1976)
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From the early 1950s onwards the road to proposals
of an RNA World was paved by
1)The embracement of the idea that primitive life had RNA
genomes (Haldane, Bernal, Pirie, Oparin, Belozerki, Brachet,
Lipmann);
2)In the context of an evolutionary biochemistry, proposals of an
ancestral metabolism catalyzed by ribonucleotidyl coenzymes
were made (Belozerski, Eakin, Handler, Orgel, White III);
3)The awareness of the complex tertiary structures of RNAs and
their key roles in protein biosynthesis (Smithies, Crick, Orgel)
cf. Lazcano (2012) Hist.Phil.Life Sci. 34: 407
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The RNA World hypothesis: the outcome of biological
intuition, an evolutionary framework, and molecular
biology
catalytic RNA
replicative RNA
Cf. Rich (1962), Woese (1967), Crick (1968) & Orgel (1968)
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Biological catalysis: enzymes & ribozymes
Hernández-Morales, Becerra & Lazcano (submitted)
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Large Subunit(PTC)
Small Subunit(decoding)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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(rRNA, tRNA, primer RNA)
ribonucleotidescoenzymes
alarmones
histidine
RNA
coding RNA (cRNA)
(riboswitches)
non-coding RNA
(nc RNA)
deoxyribonucleotides
ribose-P, amino acids, CO2, NH3
large nc RNA small nc RNA
(Argonaute/Piwi RNA)
RNA and ribonucleotides: stepping out of the shadows
Lazcano (2014)
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Cyclic adenosine monophosphate
(cAMP)
Histidine
Are modified ribonucleotides evolutionary vestiges
of ancestral biochemical stages?
Flavin adenine dinucleotideLazcano (2014)
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What is the RNA World?
There are many definitions of the RNA World,
including several contradictory ones. One could
say that it is an early, perhaps primordial, stage
during which RNA molecules played a much
more conspicuous role in heredity and
metabolism.
The role of ribonucleotides and modified
ribonucleotides as components of the RNA
World should also be considered.
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The catalytic, regulatory & structural
properties of RNA molecules, combined
with their ubiquity in cellular processes,
are consistent with the proposal that they
played a key role in early evolution and
perhaps in the origin of life itself.
Even if this possibility is not accepted, the
origin and the manifold roles of RNA in
extant biology need to be addressed
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The heterotrophic theory of the origin of life:
a contemporary reassessment
reducing atmosphere
synthesis of organic compounds
& formation of the primitive soup
coacervates
anaerobic heterotrophic bacteria
synthesis & accumulation of
organic compounds
RNA World
DNA/RNA/protein cells
Oparin 1924, 1936 Lazcano 2014
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The past is not dead. It is not
even past
William Faulkner
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How did the RNA world came into being?
A key issue in the study of the origin
and very early evolution of life:
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How did RNA originate?
Krishnamurthy 2015
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DNA, RNA & proteins
?
RNA & protein biosynthesis
RNA World
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Haeckel’s scheme of cosmic evolution
condensation of the hydrosphere
formation of the Earth
solar nebula
spontaneous
generation
cf. Lazcano (2016) J. Mol. Evol. 83: 214
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Meinert et al (2016)
Low-temperature chemical synthesis of sugars under
simulated interstellar conditions
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Copper et al (2001)
Sugar derivatives in the 4.6 x 109 yrs-old Murchison meteorite
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Abiotic synthesis of sugars via the formose reactions