The work presented in this paper essentially focuses at providing a scientific theory to explain the growth of information bearing molecules (size and information contents) without the need of any enzymatic system. It infers the footprints of molecular evolution in the cell interior for a property common to all life forms. It is deducted that molecular crowding is a vital cellular trait common to the all types of cells (primitive or highly evolved). It is argued that this trait is pervasive and must have been incorporated at some stage as a common vital feature of life. If this feature has central importance it must have been part of the pre-biotic information growth of information bearing molecules. The thermodynamic consequences of molecular crowding on the growth of RNA (50-100bp long) in the absence of enzyme system were calculated.
Deep Dive into Thermodynamic consequences of molecular crowding in information growth during pre biotic evolution.
The work presented in this paper essentially focuses at providing a scientific theory to explain the growth of information bearing molecules (size and information contents) without the need of any enzymatic system. It infers the footprints of molecular evolution in the cell interior for a property common to all life forms. It is deducted that molecular crowding is a vital cellular trait common to the all types of cells (primitive or highly evolved). It is argued that this trait is pervasive and must have been incorporated at some stage as a common vital feature of life. If this feature has central importance it must have been part of the pre-biotic information growth of information bearing molecules. The thermodynamic consequences of molecular crowding on the growth of RNA (50-100bp long) in the absence of enzyme system were calculated.
While talking about evolution, one should start with Charles Darwin who published Origin of species in 1959. The theory gave birth to the new scientific principle and emphasized that the life evolves under selection pressure and has a direction. Subsequent development not only reinforced the Darwinian evolutionary concept but also shifted the focus of attention on problem of 'Origin of life'. Towards quest of origin of life, there is contribution of enormous scientists e.g. Miller established amino aced syntheses, then synthesis of nucleic acids, and stable polymers such as polypeptides 1 , and polyamino acids were reported 2 . Then the problem of self replication and information crisis came i.e. how genetic codes (RNA or DNA) were formed when there were no enzymes (proteins) or how enzymes were formed without RNA the chicken an egg problem. It was though possible to form RNA polymer by activating imidazdlide nucleotide bases in presence of Zn was Pb ions in absence of enzyme, but in this way the polynucleotide sequences of RNA was restricted to 20 to 40 base long 3,4 . For self replication machinery to evolve in the primordial soup, the information contents of RNA in the absence of Enzyme, in terms of the size of the genetic code, should be much larger 5 .
The availability of large information of RNA I crucial as only then the primitive replicate could be translated. These inferences can be drawn by the experiments done 6,7 .
In these experiments it was found that the enzyme Qb replicase enzyme in presence of the four energized substrate nucleotide, ATP, GTP, UTP and CTP, and synthesizes RNA, even if no RNA template is present. Q replicase enzyme is in tern coded by β 4500 base long genome of Q virus. These results on one hand have shown that β evolution of self replication, in the presence of primitive replicate type of enzyme, would have been the sequence preceding evolution of eth cell. But, one the other hand, no explanation came forth, so far, to explain the mechanism of RNA (4500 base long) synthesis, in the absence of the enzyme, for the evolution of the information contents large enough to provide the code for a evolution of the information contents large enough to provide the code for a primitive replicase enzyme system. It means how RNA of size 4500 bas long is made, in absence of enzyme remain a crucial missing piece in the quest to explain prebiotic evolution of enzyme remains a crucial missing piece in the quest to explain prebiotic evolution of self replicating molecular mechanism. In present work we propose to evolve of self replicating molecular mechanism. In present work we propose to evolve a theory which beyond reasonable doubt explains the growth in information, in the absence of enzyme system. If only one assumes that this information crisis somehow was resolved, only then, the rest of the steps leading to the emergence of the self replicating machinery would fall in place.
Our theory tries to bridge the gap between 20-40 base long RNA to 4500 base long RNA, in absence of the enzyme the theory is based on thermodynamics of crowded solutions and takes into accounts fundamental traits common to all life form. The proposed theory includes the thermodynamics of molecular crowding and its consequences on the reacting kinetics.
Most of the reaction so far done is in test tube in very dilute condition. The scientific basis and rationale to consider the molecular crowding as central factor comes from the fact that biological reactions are generally performed in very crowded condition, as there are has many macromolecules within cell. The condition inside cell is thermodynamically non-ideal and has significant 8 bearing on chemical kinetics of reaction occurring under such condition 9,10 there are many biochemical reaction which have shown to be increased by molecular crowding e.g. blunt end ligation by DNA ligase increased 1000 times in presence of polyethylene gycol (PEG) crowding 11 .There are many more examples of biochemical processes occurring many fold more in crowded condition like amino acid solubility increases in presence of high concentration of PEG 12 gelling tendency of sickle shaped haemoglobin enhances in presence of non gelling proteins 13 , the activity coefficient of cytoplasmic condition of E. coli changed with addition of PEG 14 . Likewise there is a possibility of crowding playing a significant role in increasing RNA size.
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The calculations of chemical potential was done for varying conditions, shown in table, for different sized of polyp varied from 2,4,10,20,50, and 100 base pairs. The basis of selecting size below 100 base pairs falls within the con-evidence for the growth f RNA, in the absence of enzyme, under simulated prebiotic conditions 15,16 .
The size of polypeptide chain was also varied from 2, 4,10,20,50 and 100 base pairs long. Experimental evidence validates the presence of the large amount of polypeptides (PP), of diverse sizes, during prebiotic mol
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