The Origin of Genetic Systems

I. Genetic systems and the origins of life

A. Self-replication mechanism can be thought of as independent of cellular physiology, therefore, replication may have evolved independently of other metabolic pathways.

B. Genetic takeover hypothesis — inorganic replication

C. RNA can be self-catalytic. RNA-World hypothesis requires RNA to evolve first with DNA use occurring later.

Ribozyme is the abbreviation for RNA enzyme. The fact that RNA has catalytic activity was discovered by Thomas Cech (1986) in the study of how the eucaryotic rRNA genes containing introns are spliced in the ciliated protozoan Tetrahymena thermophila. Some RNAs can act as their own enzyme, that is they help catalyze reactions involving the addition of molecular parts to themselves.

D. DNA is more stable than RNA, perhaps conferring a Darwinian (selective) advantage as the genetic information carrier.

Histone proteins are related to thermally stable proteins. This may indicate thatThermoplasma or other thermophiles were primitive.

E. The existing triplet code is redundant, giving clues as to its development from simpler versions.

II. RNA and DNA as molecules

A.Molecular structure: subunits

• 5 carbon sugars: Ribose/deoxyribose
• There are five nitrogeneous bases
• Phosphates link the nucleoside sequence
• Nucleosides and nucleotides
• Hydrogen bonding between purines and pyrimidines

B. Kinds of RNA

1. Messenger RNA (mRNA).

2. Transfer RNA (tRNA).

3. RNA enzyme (ribozyme).

III. Replication in today’s cells

A. Classic cell divison

1. Mitosis
2. Division sequence
3. The cell cycle: Interphase and Mitotic Phase
4. G1, S, G2, Mitosis, Cytokenesis

B. Replication mechanism of the DNA in the chromosome

3’ to 5’ end

requirements of RNA primer,

helicases — unwind DNA strands

single-strand binding proteins — keep strands apart

top isomerases — remove kinks

RNA primers needed to initiate replication

C. Protein synthesis in the cell

• mRNA
• Ribosomes
• tRNA

IV. RNA World

1. 1986 - Thomas Cech (Boulder) discovers RNA as enzyme, a ribozyme
2. RNA molecule that catylizes a reaction joining pieces of other RNAs
3. RNA is less stable than DNA, hence thought to be more flexible
4. Ribosomes are composed on a mix of proteins and RNA subunits. In ribosomes (the site of amino acid attachment to form protein), it is the RNA subunits that form the active binding sites used for amino acid attachment.

B. (from Orgel)
“Quite recently Szostak found even stronger evidence that an RNA molecule produced by prebiotic chemistry could have carried out RNA replication on the early earth. He started by creating a pool of random oligonucleotides, to approximate the random production presumed to have occurred some four billion years ago. From that pool he was able to isolate a catalyst that could join together oligonucleotides. Equally important, the catalyst could draw energy for the reaction from a triphosphate group (three joined phosphates), the very same group that now fuels most biochemical reactions in living systems, including nucleic acid replication. Such a resemblance supports the idea that an RNA molecule could have behaved like, and preceded, the protein catalysts that today carry out the replication of genetic material in living organisms. Much remains to be done, but it now seems likely that some kind of RNA-catalyzed reproduction of RNA will be demonstrated in the not too distant future.

Studies of ribosomes, often called the protein factories of cells, have provided support for another important part of the RNA-world hypothesis: the proposition that RNA could have created protein synthesis. Ribosomes, which consist of ribosomal RNA and protein, travel along strands of messenger RNA (single-strand transcripts of protein-coding genes carried by DNA). As the ribosomes move, they link one specified amino acid to the next by forming peptide bonds between them. Harry F. Noller, Jr., of the University of California at Santa Cruz has found that it is probably the RNA in ribosomes, not the protein, that catalyzes formation of the peptide bonds.”

V. Origin of the genetic system

A. Simpler subset theories. The difficulty is that we see the genetic system today as involved both in the duplication of information and in the direct manifestation of that information being translated and transposed into protein synthesis.

1. The reduced code set.

2.Template and Sequence Directed (TSD) model of Lahav and Nir (1997). In this 6 stage model, minerals begin to catalyze random peptide formation by organic molecules. In a step-wise manner, each phase of the process preceeds to the condition whereby both the template directed (information) and amino acid (sequence) come under control of the organic system. This has the advantage of not supposing a mineralogical physiology.

B. Bait and switch theories

1. Genetic takeover theory of Cairns-Smith. Clays first, then a sequential takeover of this function by organic compounds. This theory focuses first on the information transfer capabilities of montmorillonite clays.

2. Mineral template models. The charge distribution on clays, apatite, or gypsum could act to align an m-RNA-like polynucleotide and allow hydrogen bonding to occur with opposite strands, generating a copy. Cyclic patterns in the local environment, such as temperature, could periodically break the H-bonds and rebuild RNA copies.

3. Inclusion of mineral templates into protocell systems (within a plasma membrane?)

Web Resources

• How to make RNA, by Jeff Otto.
• A short announcement about the ability to RNA to construct nucleotides.
• An article by Leslie Orgel about the RNA-world and the origins of life.