Supplemental material, sj-xlsx-2-evb-10.1177_11769343231169377 for Worldwide Correlations Support COVID-19 Seasonal Behavior and Impact of Global Change by Nicolas Hernandez and Gustavo Caetano-Anollés in Evolutionary Bioinformatics

Supplemental material, sj-xlsx-2-evb-10.1177_11769343231169377 for Worldwide Correlations Support COVID-19 Seasonal Behavior and Impact of Global Change by Nicolas Hernandez and Gustavo Caetano-Anollés in Evolutionary Bioinformatics

¹Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ∼3.5 billion years ago while the tRNA-independent counterpart emerged ∼500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.¹Current address: Biochemical Engineering Institute, Saarland University, Campus A 1.5, 66123 Saarbrücken, Germany

¹Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ∼3.5 billion years ago while the tRNA-independent counterpart emerged ∼500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.¹Current address: Biochemical Engineering Institute, Saarland University, Campus A 1.5, 66123 Saarbrücken, Germany