GADV

PROTEIN WORLD HYPOTHESIS

ON THE ORIGIN OF LIFE

PRESENTED BY

ADAM.S

AMULYA KUMAR

DR. KENJI IKEHARA

INTRODUCTION

The concept of RNA as a primordial molecule can be found in papers by

Francis Crick and Leslie Orgel,as well as in Carl Woese's 1967 book The

Genetic Code.

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in

1986,

RNA World hypothesis is widely accepted still now, as an idea by which the

origin of life might be explained. But, there are many weak points in the

hypothesis.

In contrast, Ikehara(2002) proposed a more reasonable [GADV]-protein

world hypothesis or GADV hypothesis, suggesting that life originated from

the protein world, which was formed by pseudo-replication of [GADV]-proteins.

DRAWBACKS OF RNA WORLD HYPOTHESIS

It is very difficult to prebiotically synthesize nucleotides, building blocks ofRNA, since nucleotides are rather complex organic compounds composed ofsugar, nucleobase and phosphate.

Nucleotides are unstable underthe conditions on the primitive earth. Infactnucleotides have not been detected in meteorites.

RNA could not be self replicated due to the self-discrepancy between RNAcatalysts with stable tertiary structure and RNA templates without structures.

Even if RNA were self replicated, it is also quite difficult for the self-replicatedRNA to carry genetic information because genes would never be formed byrandom polymerization of nucleotides.

It is not statistically expected for RNA randomly polymerized in the RNA worldto encode a functional water-soluble globular protein since genes are organizedby a linear arrangement of triplet base sequences or codons encoding thecorresponding amino acids.

It is also quite difficult to explain evolutionary processes of the fundamental lifesystem , composed of genes, genetic code, and proteins according to RNA worldhypothesis, since the capability of RNA for self –replication is not relevant tothe genetic code or triplet codon sequences for protein synthesis.

GADV HYPOTHESIS

GADV : The four amino acids – Gly [G], Ala [A], Asp [D], and Val [V].

It is a novel hypothesis for the origin of life, assuming that life on the

earth originated from "[GADV]-protein world", not from the "RNA world"

(see Ikehara's review, 2002).

The [GADV]-protein world is constituted from peptides and proteins

with random sequences of four amino acids (glycine [G], alanine [A],

aspartic acid [D] and valine [V]), which accumulated by pseudo-

replication of the [GADV]-proteins.

GADV hypothesis, suggesting that life originated from the protein

world, which was formed by pseudo-replication of [GADV]-proteins

STRUCTURE

Glycine(G) Alanine(A)

Aspartic acid(D)Valine(V)

PROPERTIES OF [GADV ]-AMINO ACIDS

G,A,D & V are simple organic compounds having one hydrogen atom ,

positive amino & negative carboxylic groups, and a side chain at α-carbon

atom, and all of them are easily synthesized in Miller’s discharge

experiments.

In addition, enough amounts of [GADV]-amino acids could be

accumulated on the primitive earth , since the amino acids are enough

stable for a long time under prebiotic heat conditions.

Moreover, peptide bond, which is formed between group of one amino

acid and carboxyl group of other amino acid, has a planar character,

which is favorable for folding polypeptide chain into regular secondary

structures and successively into tertiary structures, pre requisitely

required to form catalytic centre on the surface of tertiary structure.

MILLER’S EXPERIMENT

ZERO-ORDER PROTEIN STRUCTURE HYPOTHESIS

Structure formability is the same for any protein of the same

amino acid composition, that was

randomly selected for assembling.

This means that every protein synthesized by random peptide

bond formation among amino acids in the amino acid

composition could be folded into similar but into different

structures.

Proteins can have the same amino acid composition but

different sequences.

We call such a specific amino acid composition that is

favorable for protein structure formation “protein 0th-order

structure”.

ZERO-ORDER PROTEIN STRUCTURE HYPOTHESIS

In other words, according to this concept, entirely

new proteins could be produced at a high

probability in the absence of any genetic function if

proteins can be synthesized in the specific amino

acid composition.

PSEUDO REPLICATION AND PROTEIN ZERO ORDER

STRUCTURE

EXPLANATION

The reason is because proteins composed of roughly

equal amounts of [GADV]-amino acids satisfy the four

conditions (hydropathy, α-helix, β-sheet, and turn/coil

formabilities) for folding polypeptide chains into water-

soluble globular structures.

GC-NSF HYPOTHESIS ON CREATION OF GENES ON THE

PRESENT EARTH

JUSTIFICATION OF GADV HYPOTHESIS ABOUT

THE ORIGIN OF LIFE

GADV hypothesis is consistent with three general

principles for the emergence of significant organization.

General Principle 1: From Simple to Complex Molecules.

General Principle 2: From Random to Well-organized

Processes

General principle 3: From Catalytic to Genetic Functions

A POSSIBLE EVOLUTIONARY PATHWAY OF THE LIFE

SYSTEM

COMPARISION

Emergence of Life

POSSIBLE STEPS TO THE EMERGENCE OF LIFE

1. [GADV]-protein world was created by pseudo-replication of

[GADV]-proteins, route 1 route 2 Int. J. Mol. Sci. 2009, 10

1535 which were generated by random polymerization of

[GADV]-amino acids in the absence of any gene.

Formation of the [GADV]-protein world by pseudo-replication

of [GADV]-proteins introduced the first life on the primitive

Earth.

2.The GNC primeval genetic code was created through a

specific interaction between [GADV]-amino acids and GNC-

containing oligonucleotides.

3.The most primitive single-stranded (GNC)n gene was created

by random concatenation of GNC.

4. After the emergence of the first double-stranded (GNC)n

gene, [GADV]-proteins were produced, according to the codes

of diverse (GNC)n genes created from both sense and anti-

sense codon sequences.

5. Genes, genetic code, and proteins co-evolved from (GNC)n

primeval genes, GNC primeval genetic code, and [GADV]-

proteins, respectively.

As the results, the modern life system was created comprising

(NNN)n genes, the universal genetic code, and modern

proteins, transformed through primitive (SNS)n genes, SNS

code, and SNS-encoding proteins, respectively.

POSSIBLE STEPS TO THE EMERGENCE OF LIFE

PREBIOTIC SYNTHESIS

• GADV AA SYNTHESIS

• GADV P SYNTHESIS

GADV PROTEIN WORLD

GADV AA SYNTHESIS GADV P

•GADV P WITH GADVP

NUCLEOTIDE SYNTHESIS WITH GADV P

• OLIGONUCLEOTIDE SYNTHESIS WITH

GADVP

PSEUDO ORDER REPLICATION

SYNTHESIS OF BUILDING BLOCKS LED

TO THE EMERGENCE OF LIFE

WITHOUT HELP OF GENETIC

FUNCTIONS

ESTABLISHMENT

OF GNC PRIMEVAL

GENETIC CODE

CREATION OF

FIRST RNA GENE

CREATION OF GENETIC

SYSTEM

OQOL 2014 (AT INTERNATIONAL INSTITUTE FOR ADVANCED STUDIES, KIZUGAWA-SHI, JULY

12 (SAT.)-13 (SUN), 2014) [GADV]-PROTEIN WORLD HYPOTHESIS ON THE ORIGIN OF LIFE,

KENJI IKEHARA NARA STUDY CENTER, THE OPEN UNIVERSITY OF JAPAN, FELLOW OF

INTERNATIONAL INSTITUTE FOR ADVANCED STUDIES, JAPAN (ORAL PRESENTATION).