Prebiotic competition and evolution in self-replicating polynucleotides can explain the properties of DNA/RNA in modern living systems.

BACKGROUND: We hypothesize prebiotic evolution of self-replicating macro-molecules (Alberts, Molecular biology of the cell, 2015; Orgel, Crit Rev Biochem Mol Biol 39:99-123, 2004; Hud, Nat Commun 9:5171) favoured the constituent nucleotides and biophysical properties observed in the RNA and DNA of modern organisms. Assumed initial conditions are a shallow tide pool, containing a racemic mix of diverse nucleotide monomers (Barks et al., Chembiochem 11:1240-1243, 2010; Krishnamurthy, Nat Commun 9:5175, 2018; Hirao, Curr Opin Chem Biol 10:622-627), subject to day/night thermal fluctuations (Piccirilli et al., Nature 343:33-37, 1990). Self-replication, like Polymerase Chain Reactions, followed as higher daytime thermal energy "melted" inter-strand hydrogen bonds causing strand separation while solar UV radiation increased prebiotic nucleobase formation (Szathmary, Proc Biol Sci 245:91-99, 1991; Materese et al., Astrobiology 17:761-770, 2017; Bera et al., Astrobiology 17:771-785, 2017). Lower night energies allowed free monomers to form hydrogen bonds with their template counterparts leading to daughter strand synthesis (Hirao, Biotechniques 40:711, 2006). RESULTS: Evolutionary selection favoured increasing strand length to maximize auto-catalytic function in RNA and polymer stability in double stranded DNA (Krishnamurthy, Chemistry 24:16708-16715, 2018; Szathmary, Nat Rev Genet 4:995-1001, 2003). However, synthesis of the full daughter strand before daytime temperatures produced strand separation, longer polymer length required increased speed of self-replication. Computer simulations demonstrate optimal polynucleotide autocatalytic speed is achieved when the constituent nucleotides possess a left-right asymmetry that decreases the hydrogen bond kinetic barrier for the free nucleotide attachment to the template on one side and increases bond barrier on the other side preventing it from releasing prior to covalent bond formation. This phenomenon is similar to asymmetric kinetics observed during polymerization of the front and the back ends of linear cytoskeletal proteins such as actin and microtubules (Orgel, Nature 343:18-20, 1990; Henry, Curr Opin Chem Biol 7:727-733, 2003; Walker et al., J Cell Biol 108:931-937, 1989; Crevenna et al., J Biol Chem 288:12102-12113, 2013). Since rotation of the nucleotide would disrupt the asymmetry, the optimal nucleotides must form two or more hydrogen bonds with their counterpart on the template strand. All nucleotides in modern RNA and DNA have these predicted properties. Our models demonstrate these constraints on the properties of constituent monomers result in biophysical properties found in modern DNA and RNA including strand directionality, anti-parallel strand orientation, homochirality, quadruplet alphabet, and complementary base pairing. Furthermore, competition between RNA and DNA auto-replicators for 3 nucleotides in common permit states coexistence and possible cooperative interactions that could be incorporated into nascent living systems. CONCLUSION: Our findings demonstrate the molecular properties of DNA/RNA could have emerged from Darwinian competition among macromolecular replicators that selected nucleotide monomers that maximized the speed of autocatalysis.

Evolutionary advantage of anti-parallel strand orientation of duplex DNA.

DNA in all living systems shares common properties that are remarkably well suited to its function, suggesting refinement by evolution. However, DNA also shares some counter-intuitive properties which confer no obvious benefit, such as strand directionality and anti-parallel strand orientation, which together result in the complicated lagging strand replication. The evolutionary dynamics that led to these properties of DNA remain unknown but their universality suggests that they confer as yet unknown selective advantage to DNA. In this article, we identify an evolutionary advantage of anti-parallel strand orientation of duplex DNA, within a given set of plausible premises. The advantage stems from the increased rate of replication, achieved by dividing the DNA into predictable, independently and simultaneously replicating segments, as opposed to sequentially replicating the entire DNA, thereby parallelizing the replication process. We show that anti-parallel strand orientation is essential for such a replicative organization of DNA, given our premises, the most important of which is the assumption of the presence of sequence-dependent asymmetric cooperativity in DNA.

Chiral Monomers Ensure Orientational Specificity of Monomer Binding During Polymer Self-Replication.

Biomolecular homochirality is universally observed in living systems but the molecular and evolutionary dynamics that led to its emergence are unknown. In fact, there are significant disadvantages in using chiral monomers for polymerization, which include enantiomeric cross-inhibition in racemic medium and under-utilization of available resources for self-replication in the primordial environment. Nevertheless, most investigations of homochirality in living systems assume that the individual primordial monomers were chiral prior to the formation of self-replicating polymer and therefore focus on identifying a symmetry-breaking mechanism that might choose one enantiomer over the other in a racemic medium. Within the premise that the extant biomolecules are products of molecular evolution, we ask a related but distinct question: why is an achiral monomer molecule disfavored? Here we identify an evolutionary advantage for molecular evolution to choose chiral over achiral monomers to construct primordial self-replicating polymers. We argue that when polymerization is constrained to proceed in only one direction along the template, as in DNA, evolution favors chiral monomers and homochiral polymers. This evolutionary advantage stems from the ability of a chiral monomer to bond with the template in only one orientation relative to the template monomer, along the direction of polymerization. An achiral monomer, on the other hand, offers more than one possible orientation for bonding with the template monomer, due to the presence of symmetry elements in its structure, which would lead to inhibition of polymerization. We show that the requirement of orientational specificity leads to monomer chirality, by using a known relationship between rotational and reflection symmetry elements, within the constraint that the resultant polymers are helical.

Evolutionary advantage of directional symmetry breaking in self-replicating polymers.

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, DNA's 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. Within our model, circular strands, the configuration prefered by primitive life forms, have higher replicative potential compared to linear strands.

In-plane uniaxial magnetic anisotropy in (Ga, Mn)As due to local lattice distortions around Mn²âº ions.

We theoretically investigate the interplay between local lattice distortions around the Mn(2+) impurity ion and its magnetization, mediated through spin-orbit coupling of holes. We show that the tetrahedral symmetry around the Mn(2+) ion is spontaneously broken and that local Jahn-Teller distortions coupled with growth strain result in uniaxial magnetic anisotropy. We also account for the experimentally observed in-plane uniaxial magnetic anisotropy rotation due to variation of hole density. According to this model, lack of inversion and top-down symmetries of (Ga, Mn)As layers lead to in-plane biaxial symmetry breaking in the presence of Jahn-Teller distortions.