Zachary F. Burton

The Paleocene–Eocene Thermal Maximum

The Paleocene–Eocene Thermal Maximum occurred about 55.8 million years ago. Global warming rose by about 5 ° C and ocean pH dropped by about 0.5 units.

Eukaryotic Multi-Subunit RNA Polymerases, General Transcription Factors, and the CTD

With many additions, eukaryotic transcription systems evolved from archaeal transcription systems. Eukaryotes have RNA polymerases I, II, and III, with a carboxy terminal domain (CTD) repeat (YSPTSPS) on RNA polymerase II. Beginning with the intron-splicing apparatus, an extensive interactome evolved to function with the CTD. Tracking RNA polymerase II through the transcription cycle requires the CTD and the CTD interactome, and the eukaryotic cell cycle was evolved from the RNA polymerase II transcription cycle. Much of eukaryote cell and organism complexity and intricate eukaryotic signaling evolved from RNA polymerase II transcription systems.

Computers in Biology

To appreciate protein structure/function/evolution/dynamics, you need a computer: a PC or Mac will do. You do not need a supercomputer initially. This is the best art and science. Perusing a protein structure is like visiting Mars, only more alive, more essential, more human.

LEGO (Trademark) Life

The story of genesis of life on earth is preserved as written history. The remarkable story remains written in genetic code, protein secondary structure, and protein tertiary structure. This is a language that can be read by anyone (no PhD necessary, although perhaps helpful). The story has now largely been decoded.

Promoter Proximal Pausing and the CTD Interactome

The promoter-proximal pausing mechanism, found in only complex animals, is an evolutionary innovation in the RNA polymerase II CTD interactome. Because promoter-proximal pausing allows nuanced and complex gene regulation, this system helps direct development of complex body patterns. Not surprisingly, cancers and viral infections target the promoter-proximal pausing mechanism.

The RNA World

The presumed RNA world was a time largely dominated by RNA and ribozymes before evolution of the tRNA cloverleaf, the ribosome and RNA-directed protein coding.

The Chemical Synthesis of Life

The many necessary transitions from chemistry to energy transduction to polymers to coding to protocells to DNA genomes to cellular life are mostly unknown but appear to have occurred rapidly over a few hundred million years on earth. Harnessing redox power and chemical energy was essential. Generation of polymers and then coding and replicating polymers was essential.

General Transcription Factors and Promoters

The last universal common ancestor (LUCA) promoters and general transcription factors evolved via iteration of a small number of simple DNA sequences and interacting protein motifs. Divergence of archaeal and bacterial transcription systems from LUCA describes why archaea and bacteria became separate domains. Archaeal transcription factor B (TFB) and bacterial σ factors are homologs that include homologous helix-turn-helix domains that locate to homologous regions of archaeal and bacterial promoters. TFB-σ homology appears, therefore, to root the “tree of life” at LUCA.

What This Book Is About

The intention of this book is to provide a simple, verifiable understanding of evolution of life on earth. The argument, at its core, is frighteningly simple: (1) our “designs” are surprisingly simple and not obviously “intelligent”; (2) RNA synthesis describes evolution; (3) evolution describes RNA synthesis; and (4) evolution of seemingly overly complex protein synthesis systems can be simply modeled. Therefore, evolution can be viewed by understanding mechanisms of RNA and protein syntheses. Before DNA genomes, life passed through a strange RNA-protein world. RNA-template-dependent RNA polymerases of the two double-Ψ–β-barrel types (described in detail in this book) became the dominant enzymes for RNA synthesis. As life evolved into the DNA-template world, these enzymes evolved to become DNA-template-dependent RNA polymerases and spread to all cellular life. RNA, therefore, was and is the central coding molecule of life on earth and remains the intermediary between DNA genomes and protein catalysts. Because life comes from an RNA-protein world, mechanisms for RNA synthesis remain at the heart of life processes, and understanding RNA synthesis is a key to understand evolution.

Evolution as a Cutout Doll Problem III

The core concept of this book is that last universal (cellular) common ancestor (LUCA) and the RNA-protein world, ancient though they be, can be viewed in extant core protein motifs. By any human standard, core protein motifs are immortal. Core protein motifs go back to LUCA and beyond to the RNA-protein world. Astoundingly, ancient core protein motifs are ∼4xa0billion years old on an ∼4.6xa0billion year old earth.