Prebiotic evolution and the RNA World -...

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

Oparin’s step-wise heterotrophic origin of life

reducing atmosphere

synthesis of organic compounds

& formation of the primitive soup

coacervates

primordial heterotrophs

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

The 1953 Miller experiment

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)

The harvest of ‘53

Watson & Crick and the DNA double

helix model

S. L. Miller and the prebiotic

synthesis of amino acids

Molecular biology and the origins of life:

the prebiotic synthesis of adenine

Oró, 1960; Ferris & Orgel, 1966

Lazcano, Miller & Oró,1990

Chromatogram of NH4CN polymerization at 80 °C

Borquez, Cleaves, Lazcano & Miller (2005) Origins Life Evol. Biosph. 35:79

Borquez, Cleaves, Lazcano & Miller (2003) Origins Life Evol. Biosph. 35: 79

2,6 diaminopurine base pairs with uracil

Rios & Tor (2013)

Nucleobases of abiotic origin. Red, in prebiotic simulations;

black, meteorites and prebiotic simulations

Rios & Tor (2013)

Nucleobases of abiotic origin. Red, in prebiotic simulations;

black, meteorites and prebiotic simulations

CO2, CO, N2, H2S, H2O, CH4

CO2, NH3, H2S, H2O

amino acids, nucleobases, sugars, lipids,

oligomers of biochemical compounds

Lazcano (2006)

Szostak 2009

HCN

Fe(CN)64-

CN-Fe2+, Mg2+, Ca2+, Na+, K+,

Based on Szostak (2017) & Lazcano (2006)

Bracher 2015

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

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

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

Coupling of catalytic chemical species with

replicative processes

Replicative systems capable of generating

adaptative complexity

cf. Lazcano 2017

DNA

DNA RNA protein

DNA

DNA RNA protein

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)

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

The RNA Tie Club

Neidhart, Ingraham & Schaechter (1990)

RNA is the second most abundant cell component

“…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

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)

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

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)

Biological catalysis: enzymes & ribozymes

Hernández-Morales, Becerra & Lazcano (submitted)

Large Subunit(PTC)

Small Subunit(decoding)

(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)

(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)

(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)

(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)

(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)

(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)

Cyclic adenosine monophosphate

(cAMP)

Histidine

Are modified ribonucleotides evolutionary vestiges

of ancestral biochemical stages?

Flavin adenine dinucleotideLazcano (2014)

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.

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

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

The past is not dead. It is not

even past

William Faulkner

How did the RNA world came into being?

A key issue in the study of the origin

and very early evolution of life:

How did RNA originate?

Krishnamurthy 2015

DNA, RNA & proteins

?

RNA & protein biosynthesis

RNA World

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

Meinert et al (2016)

Low-temperature chemical synthesis of sugars under

simulated interstellar conditions

Copper et al (2001)

Sugar derivatives in the 4.6 x 109 yrs-old Murchison meteorite

Abiotic synthesis of sugars via the formose reactions