In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Bioinformatics in the School of Biological Sciences Petar Penev Defends his thesis:Ribosomal evolution at the intersection of sequence and structure Friday, April 9, 2021 5:00pm Eastern Timehttps://bluejeans.com/5757076859/ Thesis Advisor: Dr. Loren Dean Williams School of Chemistry & Biochemistry Committee Members: Dr. William C. Ratcliff School of Biological Sciences Dr. Nicholas V. Hud School of Chemistry & Biochemistry Dr. King I. Jordan School of Biological Sciences Dr. Jennifer B. Glass Earth & Atmospheric Sciences Abstract: The ribosome has a central position in the informational transfer within cells, it has produced all coded proteins that have ever existed in the history of life. Its undying presence in living organisms has allowed the ribosome to witness and archive life's history in structure and sequence. The centrality of translation ensures that loss of ribosomal function means loss of life. In that way the ribosome is at the basis of species taxonomy and provides a direct link back to the last universal common ancestor. Structures from ribosomes of Bacteria, Archaea, Eukarya reveal that all crucial elements necessary for ribosomal function are incredibly conserved across all major branches of the tree of life and form a common core. However, ribosomes also contain differences between the major domains of life. The ribosome is a unique molecular entity that has archived life's history in structure and sequence and holds answers to the earliest bifurcations in the tree of life and the origins of life. Here I establish a ribosomal protein (rProtein) database, provide tools for the study of deep branching points within the tree of life, and extend our understanding of the ribosome at these branching points. I first explore the branching point between Archaea and Eukarya by expanding on existing ribosomal sequence databases. I elucidate features of ribosomal RNA (rRNA) from the recently discovered Asgard archaeal clade, which is likely a close relative of Eukarya. The Asgard rRNA contains the common core and supersized expansion segments (ES). Some Asgard groups (Lokiarchaeota) demonstrate longer rRNA sequences than many eukaryotic rRNA, deviating from previously established patterns. I survey Asgard variability of ribosomal structure within one ES region by predicting and validating its secondary structures across Asgard species. Based on the accretion model of ribosomal evolution the structural variability data predicts that complex ESs were present in ancient ribosomes of the last Asgard and Eukarya common ancestor. Next, I propose TwinCons - a conservation score that highlights conserved, variable and diverging (signature) positions between a pair of sequence groups within alignments. I use the score to identify deep co-evolution of rRNA and rProtein between Bacteria and Archaea. Further I discover shared peptide segments within the translation and transcription systems. Next, I develop ProteoVision - a web server that connects protein sequence alignments with related topology and 3D structures. This web server provides an easy, quick, and simultaneous online study of ribosomal protein evolution through simultaneous visualization of primary, secondary, and tertiary structure. Finally, I discuss possible applications of the expanded ribosomal databases, specifically combined with the use of TwinCons to determine relative phylogenetic location of clades within the tree of life.
Petar Penev, PhD Bioinformatics