2002 Annual Science Report

University of Colorado, Boulder Reporting  |  JUL 2001 – JUN 2002

Properties of the Ribocyte (RNA Cell)

Project Summary

There are two areas of notable progress this year.

4 Institutions
3 Teams
0 Publications
0 Field Sites
Field Sites

Project Progress

There are two areas of notable progress this year.

Firstly, a theory bearing on the likelihood of initiation of the ribonucleic acid (RNA) world has been completed and published. In particular, the first potentially realistic calculations of the amount of RNA (the number of molecules of arbitrary sequence) needed to evolve particular ribozymes have been made. Obviously, the more RNA that is required, the more difficult it would have been to evolve primitive RNA cells. These calculations suggest:

    a. The number of RNA molecules required to begin to evolve ribozymes is anti-intuitively small. Thus an RNA cell (a ribocyte) is unexpectedly accessible. Zeptomoles of RNA molecules (1 zmol = 602 molecules), less than in a modern bacterium, might suffice (the zeptomole world hypothesis).

    b. Selection itself strongly shaped the RNAs available to an ancient ribocyte (RNA cell). These effects can be summarized in three maxims:

      I. The maxim of Magnitude – Newly selected RNA active sites will contain as few functional nucleotides as possible (1.6 specified nucleotides costs an order of magnitude more starting RNA).


      II. The maxim of Modularity – Newly selected RNA active sites will be folded from as many separated contiguous sequences (modules) as possible. It is statistically easier to find small, separated sequences than one large contiguous sequence of the same total size.


      III. The maxim of Minimization – The separate RNA modules folded together in 3 dimensions to compose an active site will be as equal in size as is practical. Unequal pieces imply some larger, improbable ones, so real sites will tend to contain the smallest (most equal) modules.


    Secondly, an RNA enzyme (peptidyl transferase, PT) dating from the RNA world itself is built into the large ribosomal subunit to make peptide bonds and thus all cellular proteins. We have now synthesized and tested a second-generation transition state analogue (TSA) that binds to the PT site on the ribosome. Our first TSA (which can be abbreviated by the name CCdApPuro) was of unique importance in finding and elucidating the initial crystallographic structure of the ribosome’s PT site. The new compound, called CCdApPuroC, was predicted from crystallography of the ribosome’s large subunit to be even more complementary to the real PT site. As predicted, the new compound fits the ribosome even more accurately, binds more strongly, and will serve as an even better marker for this ancient ribozyme.
  • PROJECT INVESTIGATORS:
  • PROJECT MEMBERS:
    Michael Yarus
    Project Investigator

    Robin Knight
    Postdoc

    Ico de Zwart
    Postdoc

  • RELATED OBJECTIVES:
    Objective 2.0
    Develop and test plausible pathways by which ancient counterparts of membrane systems, proteins and nucleic acids were synthesized from simpler precursors and assembled into protocells.

    Objective 3.0
    Replicating, catalytic systems capable of evolution, and construct laboratory models of metabolism in primitive living systems.

    Objective 8.0
    Search for evidence of ancient climates, extinct life and potential habitats for extant life on Mars.