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Register a new userEvolutionary advantage of a broken symmetry in autocatalytic polymers explains fundamental properties of DNA
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Added by
Hemachander Subramanian
Publication date
2016
fields
Biology
and research's language is
English
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The macromolecules that encode and translate information in living systems, DNA and RNA, exhibit distinctive structural asymmetries, including homochirality or mirror image asymmetry and $3 - 5$ directionality, that are invariant across all life forms. The evolutionary advantages of these broken symmetries remain unknown. Here we utilize a very simple model of hypothetical self-replicating polymers to show that asymmetric autocatalytic polymers are more successful in self-replication compared to their symmetric counterparts in the Darwinian competition for space and common substrates. This broken-symmetry property, called asymmetric cooperativity, arises with the maximization of a replication potential, where the catalytic influence of inter-strand bonds on their left and right neighbors is unequal. Asymmetric cooperativity also leads to tentative, qualitative and simple evolution-based explanations for a number of other properties of DNA that include four nucleotide alphabet, three nucleotide codons, circular genomes, helicity, anti-parallel double-strand orientation, heteromolecular base-pairing, asymmetric base compositions, and palindromic instability, apart from the structural asymmetries mentioned above. Our model results and tentative explanations are consistent with multiple lines of experimental evidence, which include evidence for the presence of asymmetric cooperativity in DNA.
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Due to the asymmetric nature of the nucleotides, the extant informational biomolecule, DNA, is constrained to replicate unidirectionally on a template. As a product of molecular evolution that sought to maximize replicative potential, DNAs unidirectional replication poses a mystery since symmetric bidirectional self-replicators obviously would replicate faster than unidirectional self-replicators and hence would have been evolutionarily more successful. Here we carefully examine the physico-chemical requirements for evolutionarily successful primordial self-replicators and theoretically show that at low monomer concentrations that possibly prevailed in the primordial oceans, asymmetric unidirectional self-replicators would have an evolutionary advantage over bidirectional self-replicators. The competing requirements of low and high kinetic barriers for formation and long lifetime of inter-strand bonds respectively are simultaneously satisfied through asymmetric kinetic influence of inter-strand bonds, resulting in evolutionarily successful unidirectional self-replicators.
The problem of DNA-DNA interaction mediated by divalent counterions is studied using computer simulation. Although divalent counterions cannot condense free DNA molecules in solution, we show that if DNA configurational entropy is restricted, divalent counterions can cause DNA reentrant condensation similar to that caused by tri- or tetra-valent counterions. DNA-DNA interaction is strongly repulsive at small or large counterion concentration and is negligible or slightly attractive for a concentration in between. Implications of our results to experiments of DNA ejection from bacteriophages are discussed. The quantitative result serves to understand electrostatic effects in other experiments involving DNA and divalent counterions.
Topology affects physical and biological properties of DNA and impacts fundamental cellular processes, such as gene expression, genome replication, chromosome structure and segregation. In all organisms DNA topology is carefully modulated and the supercoiling degree of defined genome regions may change according to physiological and environmental conditions. Elucidation of structural properties of DNA molecules with different topology may thus help to better understand genome functions. Whereas a number of structural studies have been published on highly negatively supercoiled DNA molecules, only preliminary observations of highly positively supercoiled are available, and a description of DNA structural properties over the full range of supercoiling degree is lacking. Atomic Force Microscopy (AFM) is a powerful tool to study DNA structure at single molecule level. We here report a comprehensive analysis by AFM of DNA plasmid molecules with defined supercoiling degree, covering the full spectrum of biologically relevant topologies, under different observation conditions. Our data, supported by statistical and biochemical analyses, revealed striking differences in the behavior of positive and negative plasmid molecules.
Statistics of Poincare recurrences is studied for the base-pair breathing dynamics of an all-atom DNA molecule in realistic aqueous environment with thousands of degrees of freedom. It is found that at least over five decades in time the decay of recurrences is described by an algebraic law with the Poincare exponent close to $beta=1.2$. This value is directly related to the correlation decay exponent $ u = beta -1$, which is close to $ uapprox 0.15$ observed in the time resolved Stokes shift experiments. By applying the virial theorem we analyse the chaotic dynamics in polynomial potentials and demonstrate analytically that exponent $beta=1.2$ is obtained assuming the dominance of dipole-dipole interactions in the relevant DNA dynamics. Molecular dynamics simulations also reveal the presence of strong low frequency noise with the exponent $eta=1.6$. We trace parallels with the chaotic dynamics of symplectic maps with a few degrees of freedom characterized by the Poincare exponent $beta sim 1.5$.
Molecular chaperones are ATP-consuming biological machines, which facilitate the folding of proteins and RNA molecules that are kinetically trapped in misfolded states for long times. Unassisted folding occurs by the kinetic partitioning mechanism according to which folding to the native state, with low probability as well as misfolding to one of the many metastable states, with high probability, occur rapidly on similar time scales. GroEL is an all-purpose stochastic machine that assists misfolded substrate proteins (SPs) to fold. The RNA chaperones (CYT-19) help the folding of ribozymes that readily misfold. GroEL does not interact with the folded proteins but CYT-19 disrupts both the folded and misfolded ribozymes. Despite this major difference, the Iterative Annealing Mechanism (IAM) quantitatively explains all the available experimental data for assisted folding of proteins and ribozymes. Driven by ATP binding and hydrolysis and GroES binding, GroEL undergoes a catalytic cycle during which it samples three allosteric states, referred to as T (apo), R (ATP bound), and R (ADP bound). In accord with the IAM predictions, analyses of the experimental data shows that the efficiency of the GroEL-GroES machinery and mutants is determined by the resetting rate $k_{Rrightarrow T}$, which is largest for the wild type GroEL. Generalized IAM accurately predicts the folding kinetics of Tetrahymena ribozyme and its variants. Chaperones maximize the product of the folding rate and the steady state native state fold by driving the substrates out of equilibrium. Neither the absolute yield nor the folding rate is optimized.
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