4.6 billion to 3.5 billion years ago

precell precell


Modern cells are very complex. For example, modern cells use proteins to catalyze their chemical reactions but the synthesis of protein depends on RNA and the synthesis of RNA depends on DNA. Since the synthesis of DNA itself depends on protein, how could the first cells function without three sets of complex molecules, DNA, RNA, and protein? It is possible that the first cells existed in an "RNA world" in which protein and DNA did not exist. Could RNA molecules have performed the functions of proteins while simultaneously serving as the first genetic code? In modern living things, RNA is still the only molecule which functions both as a genotype (a genetic code) and phenotype (determining outward appearance-many RNAs are functional by themselves and are never converted to protein). There are a number of observations which suggest that RNA was the primary functional molecule in the earliest cells.

a) Nucleotides (primarily RNA nucleotides) have very diverse roles in cells

An analysis of modern cells suggests that RNA is central to many cellular mechanisms. RNA nucleotides (the monomers which compose the chains of RNA) are essential molecules for modern cells. The molecule which cells use for virtually all of their energy transactions (ATP) is an RNA nucleotide with additional phosphate groups added. In other words, the energy which you are using at this moment to power muscle contractions, pump ions, move cilia, cause cells to divide, etc. is being derived from ATP, an RNA nucleotide with additional phosphate groups. Most "enzyme helpers" or coenzymes are either modified nucleotides or can be synthesized from nucleotides.

b) RNA molecules can act as enzymes (both those found in living cells and sequences generated in the absence of life)

Although proteins are indispensable in modern cells (for example, proteins called enzymes catalyze chemical reactions), RNA molecules can be found which perform many of the tasks done by modern proteins. In collections of random RNA sequences, some RNA molecules can be isolated which perform certain functions (such as catalyzing reactions). RNA enzymes (ribozymes) have been isolated from these random sequences that help to copy existing RNA molecules using the same reaction that proteins use in modern cells. These ribozymes can also undergo a "natural selection" of sorts in which researchers favor a certain type of ribozyme and over time these random sequences produced more efficient ribozymes which can catalyze the reaction hundreds to millions of times faster than the rate observed without the ribozyme (Bartel, 1993; Wright, 1997).

c) Ribozymes in modern cells can catalyze a diversity of chemical reactions
In the early earth, could RNA ribozymes have functioned in the conversion of RNA to DNA, the conversion of RNA to protein, and the splicing of small coding units to form functional genetic messages? This is not an unreasonable hypothesis, given that RNA molecules in modern cells perform these and other reactions. RNA continues to perform diverse functions in living cells and is most active in the cellular activities that would have been the most ancient (such as the splicing of the genetic message and the synthesis of proteins).
The reactions that modern RNA molecules isolated from living cells perform include the cutting and splicing of RNA molecules (spliceosomes, self-editing introns; Sharp, 1985; Cech, 1987; Kruger, 1982), extending the ends of chromosomes (telomerase) (Poole, 1997), the modification of the tRNAs used in protein construction (Rnase P), nucleotide insertion (Mueller, 1993), breaking triphosphate bonds for energy (srp RNA) (Jeffares, 1998) and the folding, cleavage, nucleotide modification, and assembly of ribosomal subunits (snoRNAs; Maxwell, 1995). Proteins synthesis, arguably one of the most important cellular processes, occurs at structures known as ribosomes whose RNA actually functions as a ribozyme (Steitz, 2003)

d) Ribozymes generated in the lab can catalyze a diversity of chemical reactions
Can artificial ribozymes replicate themselves? Yes and no. Although ribozymes which perform the necessary reactions in self replication have been isolated, they do not function at the levels that a precursor to a living cell would require (Bartel, 2000). Ribozymes can recognize a primer template and attach complimentary bases to the template. The ability to join RNA nucleotides to a primer has been accomplished by different ribozymes with different structures and biochemical properties. The accuracy of the addition of complementary bases was 97% and could be increased to 99% by altering the nucleotide concentrations. One ribozyme could extend the primer by 14 nucleotides (although the ribozyme itself was 189 nucleotides) (McGuiness, 2003).
In experiments without cells, ribozymes can be selected for out of random RNA sequences that catalyze chemical reactions such as nucleotide synthesis, forming carbon-carbon bonds, forming bonds that modern ribosomes must form during protein synthesis, and forming the bonds that modern tRNA synthetases (which are proteins) perform in protein synthesis, cleave phosphodiester bonds, act as RNA ligase, hydrolyze cyclic phosphates, phosphorylate RNA, transfer phosphate anhydride, perform acyl transfer, form amide bonds, form peptide bonds, form glycosidic bonds, and a number of other reactions (Bartel, 2000; Landweber, 1999, Ekland, 1996; Ekland, 1995. Green 1992, Illangasekare, 1995; Lohse, 1996; Tarasow, 1997; Bartel, 1993; Unrau, 1998).

transformation lateral transfer

How could early precells acquire additional catalytic RNA molecules? Mutations are a source of diversity in modern organisms and would have generated a diversity of RNAs in the early cells. In modern organisms, lateral transfer can also occur in which genes can move from one species into another. DNA can be exchanged between living cells and living cells can take up DNA from their environment. Viruses occasionally introduce DNA fragments from their previous host into their next host.
Early genetic systems would have experienced a very high mutation rate and a very high lateral transfer rate. As a result, "organisms" as the term is currently understood did not exist since genes could be exchanged regardless of lineage. It has been proposed that the last universal common ancestor of modern organisms was more of a community of cells rather than a single cell. Lateral gene transfer may have been the primary mechanism of evolution in these earliest cells, rather than descent with modification (Woese, 1998).

The pre-cells which began to utilize chains of amino acids (proteins) would obviously not have been able to create any specific sequence. Therefore the first proteins used by these cells could not have required for any vital functions. Then why proteins? In modern cells, there are a number of examples known in which RNA molecules interact with proteins to form a complex (such as the ribosome and spliceosome). The proteins function in stabilizing the three-dimensional shape of the RNA and it is the RNA which actually performs the vital function. It seems that the original function of proteins in ancestral cells was to stabilize RNA. As time went on, mechanisms were developed to control the amino acid sequence of proteins. Proteins have the advantage of being able to form more stable 3-dimensional shapes than RNA molecules can. Over time, proteins replaced most of the functions performed by ancestral RNA molecules and became the primary determinants of the phenotype of cells. However, proteins did not completely replace RNA. RNA molecules continue to perform functions in living cells such as the synthesis of proteins and the splicing of genetic messages. Although cells could conceivably use only proteins for these tasks, catalytic RNAs display what may be a conserved function from the RNA world.

The formation of proteins from individual amino acids occurs at ribosomes which are made of rRNA (ribosomal) and protein. Ribosomes must be assembled from several subunits. In a rapidly growing bacterium, ribosomes may compose 1/4 the weight of the cell. The RNA molecules which compose the ribosome are drawn in the following images.


In the following drawing of a ribosome, the RNA is depicted in blue and the small proteins which stabilize the shape of the RNA are depicted in other colors. Note the percentage of the ribosome which is composed of RNA.