The Genetic Code –MetabolismClay

A complete theory

for the Origin of Life

1971-2016

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly Ala

ProArg

Thr

Ser

Val

ILeu

Leu

Glu

Asp

Gln

Hist

Lys

Asn

Arg

Ser

Leu

PheTerm

Cys

Term

Tyr

Met

Trp

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly Ala

ProArg

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly Ala

ProArg

Thr

Glu

Asp

Gln

Hist

Lys

Asn

Arg

Ser

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly Ala

ProArg

Thr

Ser

Val

ILeu

Leu

Glu

Asp

Gln

Hist

Lys

Asn

Arg

Ser

Leu

PheTerm

Cys

Term

Tyr

Met

Trp

1

.

Origins of Life 3 423-7 (1975)

Genetic Code

G

C

A

U

CG A UG

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

Gly Ala

ProDiapr

Thr

Ser

Val

ILeu

Leu

Glu

Asp

Gln

Hist

Diapr

Asn

Diapr

Ser

Leu

PheTerm

Cys

Term

Tyr

Met

Trp

The Origin of Life and the Nature of the Primitive Gene

A.G. CAIRNS-SMITH Chemistry Department, The University of Glasgow,Glasgow, W.2, Scotland

According to the specific theory that is proposed, the primitive genographs were patterns of substitutions in colloidal clay crystallites. (The theoretical information density in such a crystallite is comparable to that in DNA.) Evolution proceeded through selective elaboration of substitutional genographs that had survival value for the clay crystallites that held them (at first through genetically controlled adsorption of a “spectrum” of organic molecules) within a complex, dynamic, primitive environment. A gradual “take-over” of the control machinery by organic macromolecules-a genetic metamorphosis-is then considered to have occurred.

J. Theoret. Biol. (1965) 10, 53-88

Metabolism

J Mol Evolution 4,359-370 (1975)

Amino acid biogenesis, evolution of the genetic code and aminoacyl-tRNA synthetasesLiron Klipcan, Mark Safro

Journal theor Biol 228(2004) 389- 396

Origin of Life and Photosynthesis

Photosynthesis

•

• Photosynthesis and the origin of life.:

• Origins of Life and the Biosphere 1998, 28(4-6):515-521

• Abstract

• . The origin of life is considered to have occurred in a hot spring on theoutgassing early earth. The first organisms were self-replicating iron-richclays which fixed carbon dioxide into oxalic and other dicarboxylic acids.This system of replicating clays and their metabolic phenotype thenevolved into the sulfide rich region of the hot spring acquiring the ability tofix nitrogen. Finally phosphate was incorporated into the evolving system,which allowed the synthesis of nucleotides and phospholipids. Ifbiosynthesis recapitulates biopoesis, then the synthesis of amino acidspreceded the synthesis of the purine and pyrimidine bases. Furthermore thepolymerization of the amino acid thioesters into polypeptides preceded thedirected polymerization of amino acid esters by polynucleotides. Thus theorigin and evolution of the genetic code is a late development and recordsthe takeover of the clay by RNA.

• Conclusion

• It there was no soup and life began as a photoautotrophic iron rich clay onEarth, then when we sample the surface of Mars for fossils of early life. Weshould look not only for amino acids and other biochemicals but also forthe ancient fossil minerals such as iron-rich clays and magnetite

The Origin and Evolutionof the Genetic Code

• In 1968 Crick stated:

• “It is almost impossible to discuss the origin of the code without discussing the origin of the actual biochemical mechanisms of protein synthesis. This is very difficult for two reasons: it is complex and many of its details are not yet understood.”

•

The Cold Spring Harbor Meeting

• ‘The Evolution of the Translational apparatus and its implications for the origin of the Genetic Code”

Starting with the ribosome

Nucleotide transferases

The Ribosome

A hierarchial model for evolution of 23S ribosomal RNAK Bobkov and S V SteinbergNature 457p 977-980 (2009)

Peeling the Onion: Ribosomes are Ancient Molecular FossilsC Hsiao et alMol.Biol.Evol. 26 2415-2425 (2009)

History of the Ribosome and the origin of translationA Petrov et alPNAS vol 112 p 15396-15401 (2015)

Ribosomal Proteins

Boston University BMERC

Temple Smith

Graduate studentsPrashanth VishnwanathPaola Favaretto

University of Texas at Austin

Robin. R. Gutell

Graduate studentJung.C.Lee

The ribosomal proteinLikely played critical roleIn early structures.

And they still do in subunitassembly

• The summary of this meeting involves

the simple idea that the translational

system evolved out a world of small

peptides and polynucleotides.

The Aminoacyl-tRNA Synthetases

tRNA

Anti-codonbinding

They must recognize both the correct amino acid and its cognate tRNA; two molecular “recognition codes”. Most tRNA synthetase have three domains.

Amino acid

As a side note, JakubowskiShowed that a few of these can transfer to a Thioester

4 55

N

C

276 35

4

abstract

Class II Aminoacyl-tRNA synthetases are a set of very ancient multi domain proteins. The evolution of the catalytic domain of Class II synthetases can be reconstructed from three peptidyl-hairpins. Further evolution from this primordial catalytic core leads to a split of the Class II synthetases into two divisions potentially associated with the operational code. The earliest form of this code likely coded predominantly Glycine (Gly), Proline (Pro), Alanine (Ala) and ‘‘Lysine”/Aspartic acid (Lys/Asp). There is a paradox in these synthetases beginning with a hairpin structure before the Genetic Code existed. A resolution is found in the suggestion that the primordial Aminoacyl synthetases formed in a transition from a Thioester world to a

Phosphate ester world.

,

Homologs of aminoacyl-tRNA synthetases acylate carrier proteins and provide a link between ribosomal and nonribosomal peptide synthesis

Marko Mociboba, et al

PNAS ∣ August 17, 2010 ∣ vol. 107 ∣ no. 33 ∣ 14585–14590

The enzymatic activity of a SerRS homologs is reminiscent of adenylation domains in nonribosomal peptide synthesis, and thus they represent an intriguing link between programmable ribosomal protein biosynthesis and template-independent nonribosomal peptide synthesis.

Thioester World

What can an organism do? What can a biosphere do?

The Seed

CO2,H20,HCO-3,H2S, N2 ,NH3, CH2O, CH3CHO

?

Can we use this algorithm to learn about the history of metabolism? Starting from a ~10,000 metabolite network (KEGG)

The phosphate-free core network counts 260 metabolites and 315 reactions

Implications…

Is this the fossil? A rich metabolism may have been present before phosphate, preparing the ground for a phosphate “explosion” and the rise of RNA and proteins

A phosphate-free network is hidden in present-day metabolism, detectable only by looking beyond organismal boundaries

The phosphate-free network is enriched with properties consistent with what we know about early metabolism, and highlights the key role of Fe-S

What other messages are hidden in metabolism?Is biopolymer-independent inheritance possible?How many “dots” are we missing?

The Evolution of the tRNA

The Origin of the RNA province

The modern t-RNA is a "tetramer" of a "monomer”(arm and

loop structure) and it is in the loop that the evolution of t-

RNA can be followed. Balasubramanian suggested that the

anti-codon loop structure 5,U...A3, was the earliest t-RNA.

In this paper we speculate that the pentamer structure was

preceded by UGCA, UGGA, UCCA and UCGA. It is further

postulated that these ancient t-RNAs were preceded by

UGC, UGG, UCC and UCG.

Speculations on the evolution of the Genetic Code III: The Evolution of tRNAOrigins of Life 14, (1984) p 643-648

The CCA enzyme

N

C

21

453

1’

D6

1

E96

D11

0

1

2

3

4

4

55

Crystal structure from, Xiong and Steitz 2004

Extracted 2D Topological secondary structure

N

C

21 453

1’D

61

E96

D110

From crystal structure,

Figure 2 in

Xiong and Steitz 2004

2D Topological secondary

structure with active site

residues marked in red

tRN

A

N

C

24

53

D61

E96

D11

0

Inserted

Simple beta Hairpin

Beta-alpha-beta Plus

Possible early assembly of CCA enzyme

core from short peptides

The Operational Code

Four Primordial modes of tRNA-synthetase recognitiondetermined by the (GC) operational code.

Sergei N Rodin and Susumu OhnoPNAS 94 p 5183-5188 (1997

The Early (G,C) Code In contrast with anticodons (and also codons), which are built offour bases, G, A, C, and U, their double-stranded precursors inthe 1-2-3 positions of acceptors appear as triplets almost invariablycomposed of G-C and C-G base pairs.

The archaic (G,C) code was hypothesized long ago . The general thesishas been argued that, like all other evolving systems, the code

“began simply and evolved to the present complexity’’ .The very fact that the anticodon/codon-like triplets in the acceptor

helix turned out to be composed of predominantly G-C and C-G base pairsstrongly supports this hypothesis.

Class II synthetase expansion

Addition ofAnti codondomain

Expanded Operationalreading

Addition ofEditing domain

Mini RNA Helix ? Or onlyXCCA ?

1H4T Bac Pro

Potential active site operational code interactionsDividing the class II into two groups

Proc Natl Acad Sci U S A. 1997 May 13; 94(10): 5183–5188.Four primordial modes of tRNA-synthetase recognition, determined by the (G,C) operational codeSergei N. Rodin and Susumu Ohno

tRNAsDiscriminator base

Operational code

Anticodon

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rodin SN[Author]&cauthor=true&cauthor_uid=9144212https://www.ncbi.nlm.nih.gov/pubmed/?term=Ohno S[Author]&cauthor=true&cauthor_uid=9144212

Our current ideas derive from the work of many others, in particular,those attending the recent Cold Spring Harbor meeting