A well-resolved pre-LUCA history of Class I aminoacyl-synthetase proteins reveals a critical link to the RNA world
Dr. Gregory Fournier, Cecil and Ida Green Assistant Professor of Geobiology
Massachusetts Institute of Technology
2:00-3:00 | Molecular Science & Engineering 3201A
Friday, December 7, 2018
Translation is one of the most ancient and essential biological processes. An important step in the process is aminoacylation, by which tRNA are loaded with the amino acid cognate to their anticodon specificity. This process is carried out in all life by two unrelated groups of proteins, Class I and Class II aminoacyl-tRNA synthetases (aaRSs), each class containing protein families with specificity for 10 of the 20 canonical amino acids. As all aaRS families are present across all 3 Domains of life, it has been inferred that the lineage containing LUCA inherited a full “modern” collection of aaRS. Therefore, these protein families must have diversified from a common ancestor pre-LUCA. While clearly homologous, extensive structural and sequence divergence within each family makes alignment and phylogenetic reconstruction extremely difficult. Previous phylogenetic reconstructions of pre-LUCA aaRS divergences have therefore only used small highly conserved regions of the proteins associated with the catalytic aminoacylation domain, leading to poorly resolved histories due to an insufficient number of informative sites. Here I present an improved alignment of Class I aaRS proteins, that recovers a much greater number of informative sites, and produces a fully resolved, robust phylogeny. Improved alignment techniques, including structure-based alignments, still consistently mis-align regions of these proteins. Therefore, a careful, site-by-site manually curated alignment was performed, with reference to structural and functional studies in the literature. The resulting phylogeny is distinctly ladderized, permitting a rooting of protein family divergences based on parsimony models for insertion and deletions. Ancestral sequence reconstruction of the root shows that all 20 amino acids were very likely already being incorporated at conserved sites within the ancestor, requiring a “modern” genetic code to predate the origin of cognate aaRS proteins. This result is only possible if the protein-based aaRS system was predated by an earlier aminoacylation coding system, implicating such a process being part of the RNA world. Additionally, we show that the best fitting evolutionary models for these ancient protein divergences resemble those empirically determined from modern proteins, and that our observed phylogeny is unlikely biased by wrongly assuming that an earlier genetic code operated by the same general substitution frequencies. This further supports that not only the amino acid alphabet, but the structure of the genetic code itself may have been similarly modern at this time. Finally, we make the surprising observation that bacterial leucyl-tRNA synthetase underwent a major recombination event early in its history, inserting its proofreading domain to a different region of the protein. Misalignments resulting from this recombination may have further confounded previous attempts at reconstructing the history of this protein family.
Seminar Presented by The Daniel Guggenheim School of Aerospace Engineering:
Seeking and Supporting Life Beyond Earth
Christopher E. Carr, Ph.D., Research Scientist, MIT Research Fellow, MGH
3:30 PM | Guggenheim Building, Room 442
Tuesday, November 27, 2018
The search for life beyond Earth is a major focus of space exploration, both robotic and human. Informed by the molecular biology revolution, exploration of extreme environments, from Earth, to icy moons, and exoplanets, are dramatically transforming our view of life in the universe. We now know that Mars was once habitable and may support life today. We are developing the Search for Extra-Terrestrial Genomes (SETG) to search for life on Mars ancestrally related to us, possibly shared by ancient impact events that transported a billion tons of rock between our worlds. Beyond Mars, we can now seriously consider missions to search for life at Enceladus, or Europa, although it will require transformational mission capabilities including a revolution in autonomy. More broadly, we now have the foundation to understand the limits of our own adaptation to space, and to augment those limits through innovative engineering, both biologically inspired, and biology-based. Building the tools required for a robotic and human future in space, on Mars, and beyond, we can simultaneously advance human health and sustainability on Earth.
Biography: Christopher E. Carr is a Research Scientist in the Department of Earth, Atmospheric and Planetary Sciences at MIT and a Research Fellow in the Massachusetts General Hospital Department of Molecular Biology. After completing dual S.B. degrees in Aero/Astro and Electrical Engineering from MIT, Dr. Carr worked on the Mars Sample Return mission at the Jet Propulsion Laboratory. As an NSF Graduate Research Fellow, Dr. Carr applied bioengineering principles to human adaptation to space, the bioenergetics of movement, and improved space-suit design. He currently serves as the Science PI for the SETG life detection instrument, also relevant to astronaut health, space biotechnology, and field research. He is broadly interested in searching for and expanding the presence of life beyond Earth.
Sustaining Life with Genes and Proteins Designed ‘From Scratch’
School of Biological Science Seminar
Dr. Michael Hecht | Princeton University
11:00-12:00| Engineered Biosystems Building 1005
Friday, November 16, 2018
October 18-19, Georgia Tech Global Learning Center
“The Georgia Department of Economic Development and Georgia Tech Center for Space Technology & Research are hosting a one-day symposium at the Georgia Tech Global Learning Center in Atlanta, GA. The symposium is planning a combination of technical presentations, panel discussions and guest speakers to highlight recent innovations in space science and technology.”
Life in the Universe
Prof. Avid Loeb, Chair, Astronomy Department, Director, Institute for Theory and Computation, Founder Black Hole Initiative, Harvard University
March 12, 2018 3:00-4:00 Marcus Nanotechnology Building . 1116-1118
Avi has a wide range of research interest, including black holes, the first stars, and the search for extraterrestrial life. Avi is the chair of the Astronomy Department, founding director of the Black Hole Initiative, director of the Institute for Theory and Computation at Harvard university, and he also chairs the Advisory Committee for the Breakthrough Starshot Initiative.
Geochemical Controls on Protocell Self-Assembly in the Origins of LifeProf. Nita Sahai, Department of Polymer Science; Department of Geology; and Integrated Bioscience Program, University of Akron, Akron, OH
March 1, 2018 10:50-11:50 Ford ES&T L1205
The focus of our work is to determine the constraints placed by atmosphere-water-rock interactions on the environmental conditions for self-assembly of the molecular building blocks of the earliest like-like entities, “protocells.” We have addressed the problem that modern geochemical concentrations of total dissolved phosphate (PT) and Mg2+ are much lower than those are required for non-enzyamtic (prebiotic) RNA synthesis, while Mg2 and Ca2+ concentrations are too high for membrane stability, so how did life emerge on early Earth? We used a geochemical thermodynamic modeling approach, to show that a single, globally-occurring geological process of komatiite rock weathering and evaporation of the resulting solutions under specific partial pressures of atmospheric CO2 (PCO2) can quantitatively provide the PT, Mg2+ and Ca2+ concentrations required for nucleotide synthesis, RNA polymerization and protocell-membrane stability. Conversely, the biologically-required concentrations of PT, Mg2+ and Ca2+ place constraints on the PCO2 levels on early Earth compared to previous estimates ranging over five orders of magnitude. Using these environmental constraints on Mg2+ and Ca2+ concentrations, we examined the stability and evolution of simple protocell membranes from pure single chain amphiphile (SCA) compositions through mixed SCA-phospholipid (PL) to pure PL compositions found in modern cells. We showed that, rather than acting being toxic, the divalent cations promoted evolution of the membranes towards more modern compositions. We also found that RNA oligomer synthesis is possible even at much lower concentrations of Mg2+ than previously reported, well within the concentration range constrained by the atmosphere-water-rock interactions. Thus, we have used a geochemical modeling approach to create the components of a simple protocell under geochemically plausible conditions.