bioRxiv Science⌕ Search

Biology subjects

Sawant, A. A.

Publications and source records attributed to Sawant, A. A..

2 recordsLinked to original sources

Cross-catalytic enhancement of peptides and RNA from a common prebiotic activated intermediate

Previous origin of life studies have demonstrated the presence of amino acids and nucleotides in the same prebiotic milieu. In this study, we set out to understand the interplay of amino acids with linear or cyclic nucleotides under prebiotically pertinent reaction conditions, especially for its implications for biomolecular evolution. We characterized the cross-catalytic effect of oligomerization, potentially stemming from the simultaneous presence of these two biochemically important monomers. Qualitative and quantitative analysis indicated the formation of longer AMP oligomers and peptides, with 8-10 fold increase in specific reaction scenarios, when compared to reactions that evaluated the monomer oligomerization in isolation. The reason behind such an increase in yield and length, in case of both the oligomers, was the formation of a reactive intermediate. This aminoacylated-AMP (AMP-aa) resulted from a condensation reaction between the nucleotide and the amino acid. We extended this to other amino acids with different R chain characteristics, to comprehend the properties required for the formation of AMP-aa under our reaction conditions. The nonenzymatic formation of these aminoacylated AMP, which in turn resulted in longer oligomers, indicates the plausibility of the emergence of initial steps involved in a primordial translation system.

biochemistry↗

A prebiotic genetic alphabet as an early Darwinian ancestor for pre-RNA evolution

RNA-based genetic code is thought to be central to lifes emergence due to its dual ability for information transfer and catalysis. Nonetheless, the genetic code of early life was potentially not restricted to canonical genetic alphabets alone. The presence of an extensive repertoire of modified nucleobases in extant biology as signatures of the past, highlights the relevance of non-canonical alphabets, ably strengthened by experiments demonstrating their ready conversion into nucleosides and nucleotides. All these strongly support a pre-RNA World, wherein informational molecules are posited to have contained alternate genetic alphabets. Nevertheless, understanding pre-RNA molecules capacity to acquire emergent function has remained less prevalent. Further, the steps involved in their transition to a canonical RNA World has not been systematically studied in the origins of life framework. In this study, we report the synthesis of a prebiotically relevant genetic alphabet containing the non-canonical nucleobase, barbituric acid. We demonstrate for the first instance the enzymatic incorporation of this prebiotically plausible alphabet (BaTP) into an RNA, using proteinaceous T7 RNA polymerase. Pertinently, the incorporation of this genetic alphabet into a baby spinach aptamer did not affect its overall secondary structure, while also allowing it to retain its aptameric function. Furthermore, we demonstrate the faithful transfer of genetic information from pre-RNA-containing barbitudine nucleotides to DNA, using a high-fidelity RNA-dependent DNA polymerase. These findings allude to a putative pathway for the early molecular evolution of the genetic code of extant life.

biochemistry↗