Protein 'big bang' reveals molecular makeup for medicine and bioengineering

Since the COVID-19 pandemic, proteins have quietly taken over our lives. The virus's "spike" protein has been mutating dozens of time to produce more deadly forms. We have lived at its will since then. The truth is that proteins have ruled us all our lives. They are responsible for almost everything at the cellular level.Proteins are so essential that DNA, the genetic material that makes us all unique, is actually just a sequence of protein blueprints. This is true for all animals, plants and fungi as well as bacteria, archaea and viruses. Proteins and their components also change and evolve over time just like these groups of organisms.Researchers at the University of Illinois have published a new study in Scientific Reports that maps the evolution and interrelationships of subunits of proteins over 3.8 billion year.Scientists could learn how and why domains in proteins combine during evolution to improve their understanding and engineering of the activity of proteins for medicine or bioengineering. These insights could help with disease management such as the development of better vaccines against the COVID-19 virus spike protein," Gustavo Caetano–Anolls, senior author of the paper and professor in the Department of Crop Sciences.Caetano-Anolls studied the evolution COVID mutations from the very beginning of the pandemic. However, that timeline is only a small fraction of the work he and Fayez Aziz did in their current research.Researchers compiled sequences of millions of protein sequences from hundreds of genomes, across all taxonomic classes, including higher organisms as well as microbes. They did not focus on whole proteins but structural domains.Advertisement"Most proteins have more than one domain. These modules are small structural units that can hold specialized functions," Caetano Anolls explains. They are also the units of evolution.After sorting proteins into domains in order to build evolutionary trees they began to create a network to study how domains developed and were shared among proteins over billions of years."We created a series of time-series networks that show how domains have been accumulated and how their domains were rearranged by evolution. Fayez Aziz states that this is the first study of such a network of "domain organization" as an evolutionary chronology. "Our survey revealed that there is an evolving network that describes how domains interact with one another in proteins."Each link in the network is a moment when a domain was recruited into protein, usually to perform a new function.Fayez Aziz states that this fact alone suggests that domain recruitment is a powerful force within nature. The chronology revealed which domains had important protein functions. The researchers were able, for example, to trace the origins domains that are responsible for environmental sensing and secondary metabolites or toxins used by bacterial and plant defenses.AdvertisementIt was found that domains began to mix early in protein evolution. However, there were also periods when networks grew rapidly. The researchers report on a "big bang", 1.5 billion years ago that saw domain combinations. This coincided with the rise in multicellular organisms, eukaryotes and organisms with membrane-bound nuclear nuclei, which include humans.It is not new to know that biological big bangs exist. The team of Caetano Anolls previously reported on the enormous and early origins of metabolism. They recently discovered it again in a study of the history of metabolic networks.New tools for understanding protein makeup are provided by the historical record of a large bang that describes the evolution of proteins.Caetano - Anolls states that this could be used to identify structural variations and genetic recombinations in SARS-CoV-2.He says that understanding proteins in a new way could prevent pandemics and help to understand how viruses are created. It could also be used to improve vaccine design in cases of outbreaks.Scientific Reports published the article "Evolution of networks protein domain organization." The National Science Foundation and U.S. Department of Agriculture supported the work.The Department of Crop Sciences can be found in the College of Agricultural, Consumer and Environmental Sciences of the University of Illinois.