SCOL Project: Evolution of Primordial Peptides, Proteins and the Genetic Code
On the path to contemporary protein-dominated biology, life on earth has gone through multiple stages that included a primitive protocell and likely an RNA World. Yet, even before life appeared, numerous amino acids have been accessible through non-biological processes. This fact has been famously demonstrated by the Urey-Miller experiment which simulated the conditions thought to be present on the early Earth. It is therefore conceivable that some of those primitive amino acids or even short peptides had been utilized since the earliest stages of life.
More than three billion years later, today’s biology is defined by the ‘universal’ genetic code that produces proteins from the ‘standard’ alphabet of twenty amino acids. From a perspective of the origin and evolution of life, the amino acid alphabet was never a fixed ‘standard’ but rather a work in progress, which likely started with a smaller subset of primitive amino acids and subsequently evolved into the alphabet of twenty we see today. Numerous studies have speculated on the genesis of amino acids and the history of the genetic code. Unfortunately, this field of research has been dominated by hypotheses and theoretical concepts but is largely lacking experimental support.
The central goal of our proposed work is to experimentally investigate this missing link between primitive non-biological amino acids and today’s highly functional proteins. We will test different primitive alphabets containing fewer and fewer amino acids for their ability to produce protein structures that possess functions important for the survival of a primitive cell. These experiments will produce critical insights into the history and evolution of the standard amino acids alphabet.
Burckhard Seelig is an assistant professor in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota. He received a master’s degree in chemistry from the Humboldt University of Berlin, Germany. He has been actively involved in research on origin of life subjects since he started graduate school with Andres Jaeschke at the Free University of Berlin. During his PhD work he generated an artificial ribozyme by in vitro selection and thereby demonstrated that RNA is capable of catalyzing a carbon-carbon bond formation reaction. This type of reaction is considered crucial for the metabolism in an RNA World. As a postdoc at Harvard Medical School with Jack Szostak, he conducted experimental work on potential scenarios for the origin of early protein enzymes. He generated enzymes de novo from a library of billions of randomized protein variants of a non-catalytic scaffold. Dr. Seelig’s research program at the University of Minnesota is centered on the origin and evolution of functional proteins using principles of Darwinian evolution in the laboratory while borrowing methods from biochemistry, organic chemistry, and molecular biology.