On the the evolution of the ribosome, the central dogma of molecular biology, and what lies beyond the root of the tree of life
Beyond the root of the tree of life, nearly 4 billion years into the distant past, lies the origin. During or near the origin of life, the onset of production of proteins of specific sequences, with well-defined structures and sophisticated functions, launched Crick’s Central Dogma of Molecular Biology. The initial translation of messenger RNA into protein set the path of biology and established the paradigm that continues to dominate the biological earth after over 3.5 billion years.
In our research we develop methods, grounded in three-dimensional structures, for reading primordial information stored deep within the ribosome. This information has guided us in building a highly detailed molecular-level model of the evolution of the ribosome. This model, which we call the “Accretion Model”, is comprehensive in that it describes the origins of the large ribosomal subunit, the small subunit, transfer RNA and messenger RNA. The model describes iterative accretion of RNA fragments in an incremental building up of gigantic ribosomes. The timeline of the Accretion Model initiates in ancient proto-biology in the initial formation of functional centers, and progresses to establishment of the genetic code and the functional integration of polynucleotide and polypeptide. The Accretion Model provides a framework to understand the rapid ongoing increase in sizes of metazoan and especially mammalian ribosomes. Of course the word ‘rapid’ must be interpreted here in the timeframe of a multi-billion year process.
In 1969, Associate Professor of Microbiology Carl Woese wrote to Nobel Laureate Francis Crick seeking moral support for an investigation of the distant past. Woese wrote:
…I would be grateful… for any backing (largely moral) you could give me… if we are ever to unravel the course of events leading to the evolution of the prokaryotic (i.e., simplest) cells… this can be done by using the cell’s “internal fossil record”. The obvious choice of molecules here lies in the components of the translation apparatus. What more ancient lineage is there?
Woese was deeply insightful in choosing to concentrate on the ribosome. No other biological system could have provided the information he sought. And it worked. In 1977, Woese and research associate George Fox shook the scientific world by announcing their discovery of a third domain of life, and by their fundamental revision of the tree of life. For determining phylogenetic relationships Woese and Fox pioneered the use of ribosomal RNA sequencing. Their method is so powerful and pervasive that there are now around 5 million rRNA sequences in the databases.
The ribosome in three-dimensions shows us that the exit tunnel was a central theme of all phases of its evolution. The tunnel was continuously extended and rigidified. The synthesis of non-coded peptides of increasing length conferred advantage as some reaction products bound to the ribosome. The ribosome sequentially gained capabilities for RNA folding, catalysis, subunit association, correlated subunit evolution, decoding and energy-driven translocation. Surface proteinization of the decoding ribosome was one driver of a more general proteinization of other biological processes, giving rise to modern biology. The ribosome spawned the existing symbiotic relationship of functional proteins and informational nucleic acids.
Our research foci are on dissecting and literally resurrecting the ancient ribosome. We formulate computational models and test them by experimentally rebuilding extinct macromolecules from the dawn of life, to regenerate ancient functions. We rewind the “tape of life” by mapping, at the molecular level, the processes by which RNA and protein joined forces to create the ribosome – a surviving functional asssembly dating from life’s origin. Through our work, we hope to reveal how the original and most profound symbiotic relationship in all of biology, that of polypeptide and polynucleotide, took place and evolved to define life as we know it.