Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?

Abstract

Background: The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO(2) producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing proposal that life arose within alkaline (pH 9-11) deep-sea hydrothermal vents like those of the 'Lost City', with the interface with the acidic ocean creating a proton gradient sufficient to drive the first metabolism. However, RNA is most stable at pH 4-5 and is unstable at alkaline pH, raising the possibility that RNA may have first arisen in the acidic ocean itself (possibly near an acidic hydrothermal vent), acidic volcanic lake or comet pond. As the Hadean Eon progressed, the ocean pH is inferred to have gradually risen to near neutral as atmospheric CO(2) levels decreased.

Presentation of the hypothesis: We propose that RNA is well suited for a world evolving at acidic pH. This is supported by the enhanced stability at acidic pH of not only the RNA phosphodiester bond but also of the aminoacyl-(t)RNA and peptide bonds. Examples of in vitro-selected ribozymes with activities at acid pH have recently been documented. The subsequent transition to a DNA genome could have been partly driven by the gradual rise in ocean pH, since DNA has greater stability than RNA at alkaline pH, but not at acidic pH.

Testing the hypothesis: We have proposed mechanisms for two key RNA world activities that are compatible with an acidic milieu: (i) non-enzymatic RNA replication of a hemi-protonated cytosine-rich oligonucleotide, and (ii) specific aminoacylation of tRNA/hairpins through triple helix interactions between the helical aminoacyl stem and a single-stranded aminoacylating ribozyme.

Implications of the hypothesis: Our hypothesis casts doubt on the hypothesis that RNA evolved in the vicinity of alkaline hydrothermal vents. The ability of RNA to form protonated base pairs and triples at acidic pH suggests that standard base pairing may not have been a dominant requirement of the early RNA world.

Figure 1

The RNA phosphodiester bond is most stable at pH 4-5 at 90°C. Hydrolysis of the dinucleoside 3',5'-UpU at 90°C as a function of pH. Figure reprinted with permission from [15] Oivanen et al. ^©1998 American Chemical Society; data used with permission from [10] Järvinen et al. ^©1991 American Chemical Society.

Figure 2

Proposed timeline of early evolution from the origin of RNA (pH 4-5) to modern life forms (pH ~7). On the right of diagram are two proposed RNA world mechanisms compatible with acidic pH (see section 'Testing the hypothesis' for details).

Figure 3

A self-cleaving ribozyme isolated by in vitro-selection has maximal activity at pH 4.2. The rate of cleavage obtained at each pH value was normalized to the maximum rate measured at pH 4.2. Figure adapted with permission from [11] Jayasena and Gold 1997 ^©1997 National Academy of Sciences, U.S.A.

Figure 4

Rate of hydrolysis of aminoacyl-tRNA decreases with pH over the range pH 6-11. Rate of hydrolysis of leucyl-tRNA at 37°C and ionic strength 0.30 (the break in the curve between pH 8-10 represents the shift from rate-determining hydroxide attack on the ammonium acid ester cation to rate-determining attack on the free amino acid ester). Figure adapted with permission from [22] Wolfenden ^©1963 American Chemical Society.

Figure 5

A possible scheme for non-enzymatic RNA replication at pH 4-5. (a) tRNA^Gly(GCC) forms dimers through its GCC anticodon due to hemi-protonation of the central cytosine at pH 4-5 [37](b) At pH 4-5, C-rich (GCC)_n sequences might produce C-rich duplicates by non-enzymatic replication. Base pairs involving hemi-protonated cytosines are indicated by (+).

Figure 6

A possible mechanism for aminoacylation specificity in the RNA world. Specificity could have been through a triple helix interaction at acidic pH between the aminoacyl stem of a tRNA/precursor hairpin (shown here as the glycine tRNA sequence) (blue) and an aminoacylating ribozyme comprised of an active variant of the 5-nucleotide ribozyme from [48] fused to a 3' polypyrimidine 'tail' (red). See text for further comments and references. X_n = nucleotide linker sequence. Base triples involving protonated cytosines are indicated by (+).