Molecular basis of Arginine and Lysine DNA sequence-dependent thermo-stability modulation.

Benjamin Martin,Pablo D Dans,Nuria Villegas,Federica Battistini,Montserrat Terrazas,Milosz Wieczór,Modesto Orozco,Isabelle Brun-Heath,Anna R Panchenko

doi:10.1371/journal.pcbi.1009749

Abstract

We have used a variety of theoretical and experimental techniques to study the role of four basic amino acids–Arginine, Lysine, Ornithine and L-2,4-Diaminobutyric acid–on the structure, flexibility and sequence-dependent stability of DNA. We found that the presence of organic ions stabilizes the duplexes and significantly reduces the difference in stability between AT- and GC-rich duplexes with respect to the control conditions. This suggests that these amino acids, ingredients of the primordial soup during abiogenesis, could have helped to equalize the stability of AT- and GC-rich DNA oligomers, facilitating a general non-catalysed self-replication of DNA. Experiments and simulations demonstrate that organic ions have an effect that goes beyond the general electrostatic screening, involving specific interactions along the grooves of the double helix. We conclude that organic ions, largely ignored in the DNA world, should be reconsidered as crucial structural elements far from mimics of small inorganic cations.

Highlights

One “dogma” originating from the early Watson-Crick models [1] is that GC-rich DNAs are more stable than the AT-rich ones [2]
Primordial soups was supposed to be enriched in basic amino acids [17,18], the proteinogenic ones Arg and Lys, and non-proteinogenic ones such as Ornithine, and L-2,4-Diaminobutyric acid (DABA)
We found that duplexes got stiffer with the increasing of the concentration of organic cations

Summary

Introduction

One “dogma” originating from the early Watson-Crick models [1] is that GC-rich DNAs are more stable than the AT-rich ones [2]. We can imagine prebiotic conditions with cycles of heat/cold opening and renaturing the duplex, mimicking a protein-free “PCR-like” auto-replication process [16] Such a process could not have been efficient if the relative stability of AT- and GC-rich duplexes was very different, as it happens in dilute aqueous conditions. Primordial soups was supposed to be enriched in basic amino acids [17,18], the proteinogenic ones Arg and Lys, and non-proteinogenic ones such as Ornithine (synthesized at high yields in Miller-Urey experiments [19]), and L-2,4-Diaminobutyric acid (DABA) We hypothesize that such amino acids could reduce the gap between AT- and GC-rich duplexes, a requirement for the self-replication of nucleic acids, the only mechanism for copying DNA information [16]. This hypothesis links with the high prevalence of arginine and lysine interactions with DNA in known protein-DNA complexes [20] (just arginine establishes more hydrogen bonds with phosphates than all the neutral amino acids together [20]) and with the ability of small Arg and Lys peptides to condensate DNA, a requirement for defining pre-biotic phases [21], as to polymerize without the presence of enzymes large concentration of building blocks are required [22]

Methods

Results

Conclusion