The emergence of DNA in the RNA world: an in silico simulation study of genetic takeover

Abstract

Background: It is now popularly accepted that there was an "RNA world" in early evolution of life. This idea has a direct consequence that later on there should have been a takeover of genetic material - RNA by DNA. However, since genetic material carries genetic information, the "source code" of all living activities, it is actually reasonable to question the plausibility of such a "revolutionary" transition. Due to our inability to model relevant "primitive living systems" in reality, it is as yet impossible to explore the plausibility and mechanisms of the "genetic takeover" by experiments.

Results: Here we investigated this issue by computer simulation using a Monte-Carlo method. It shows that an RNA-by-DNA genetic takeover may be triggered by the emergence of a nucleotide reductase ribozyme with a moderate activity in a pure RNA system. The transition is unstable and limited in scale (i.e., cannot spread in the population), but can get strengthened and globalized if certain parameters are changed against RNA (i.e., in favor of DNA). In relation to the subsequent evolution, an advanced system with a larger genome, which uses DNA as genetic material and RNA as functional material, is modeled - the system cannot sustain if the nucleotide reductase ribozyme is "turned off" (thus, DNA cannot be synthesized). Moreover, the advanced system cannot sustain if only DNA's stability, template suitability or replication fidelity (any of the three) is turned down to the level of RNA's.

Conclusions: Genetic takeover should be plausible. In the RNA world, such a takeover may have been triggered by the emergence of some ribozyme favoring the formation of deoxynucleotides. The transition may initially have been "weak", but could have been reinforced by environmental changes unfavorable to RNA (such as temperature or pH rise), and would have ultimately become irreversible accompanying the genome's enlargement. Several virtues of DNA (versus RNA) - higher stability against hydrolysis, greater suitability as template and higher fidelity in replication, should have, each in its own way, all been significant for the genetic takeover in evolution. This study enhances our understandings of the relationship between information and material in the living world.

Fig. 1

The influence of Nrr with different active rates on the system of the RNA-based protocells. (a) The Nrr’s active rate (P _NRR) is kept 0 throughout the simulation. Based on the case shown in A, at step 0.7 × 10⁶, P _NRR is changed from 0 to (b) 0.5; (c) 0.02; (d) 0.001. For each subfigure, the top panel shows the dynamics at the molecular level, and the bottom panel the cellular level. Stars represent the chromosome (RNA in black and DNA in red) containing all the five genes, while x-shapes represent the chromosome (RNA in black and DNA in red) containing only four genes (lacking the Nrr). The black dashed line denotes the total materials concerning RNA, including RNA, nucleotides, nucleotide precursors and nucleotide precursors’ precursors (all counted as quotients in measurement of nucleotides; and to be drawn in this same figure, the “materials” are here represented in a 1/200 scale); and in a similar way the red dashed line denotes the total materials concerning DNA. Dots represent the ribozymes (Rep in magenta, Nsr in green, Npsr in cyan, Asr in yellow, and Nrr in blue). Empty circles represent total protocells, and the circles with a symbol in represent the protocells containing the chromosome represented by that symbol (e.g., the circles with a black star in represent the protocells containing the five-gene RNA chromosome). Note that the symbols in the following dynamic figures are interpreted the same way

Fig. 2

Several cases showing the dynamics of the model system when the Nrr’s effect is not “applied on a global scale”. Based on the case shown in Fig. 1a, at step 1.4 × 10⁶, P _NRR is changed from 0 to (a) 0.5; (b) 0.02. Based on the case shown in B, (c) at step 1.5 × 10⁶, F _SFR is changed from 2 to 10; (d) at step 1.8 × 10⁶, P _BBR is changed from 2 × 10⁻⁶ to 2 × 10⁻⁵. Note that at step 1.4 × 10⁶, due to random mutation, apparently only a portion of the RNA chromosome molecules maintains the “non-functional” Nrr gene (see the descending of black stars, which denote the five-gene chromosome, and the rising of black x-shapes, which denote the four-gene chromosome). So when the activity of the Nrr is turned on at this moment, the Nrr’s effect is only “applied on a limited scale”. The thorough genetic takeover shown in D is in fact originated from a single individual, because at step 1.8 × 10⁶ in this case there are actually only one protocell containing the five-gene chromosome, which bears the moderate Nrr gene

Fig. 3

The stabilization of the DNA/RNA platform that is brought about by the moderate Nrr. Based on the case shown in Fig. 1c, at step 2.4 × 10⁶, (a) F _SFR is changed from 2 to 10 (the template activity of RNA is turned down); (b) P _BBR is changed from 2 × 10⁻⁶ to 2 × 10⁻⁵ (the rate of RNA’s chain break is turned up)

Fig. 4

About the causes for the genetic takeover in evolution. Based on the case show in (a), which represents an advanced system supported by a DNA genome (See text for details), at step 2 × 10⁶, (b) F _SFD is changed from 1 to 2 (the template activity of DNA is turned down); (c) P _FPDD is changed from 0.001 to 0.01 (the fidelity of DNA replication is turned down); (d) F _BBD is changed from 0.01 to 1 (i.e., DNA becomes equal to RNA in stability)

Fig. 5

Key events associated with the relation, difference and interaction between RNA and DNA. The diagram shows one grid room in the model which is occupied by a protocell. Legends: Npp, nucleotide precursor’s precursor; Np, nucleotide precursor; Nt, nucleotide; Ap, amphiphile precursor; Am, amphiphile; Dnpp, deoxynucleotide precursor’s precursor; Dnp, deoxynucleotide precursor; Dnt, deoxynucleotide; the notations of ribozymes are the same as in the text. The parameters shown in bold type are those newly introduced which are explained in Table 1, and the others are “old ones” whose descriptions can be found in Table 2. Note that while the rate of chain breaking (hydrolysis) for RNA is represented by P _BBR, that for DNA is defined as P _BBR × F _BBD – wherein, F _BBD < <1. The tendency of a nucleic acid chain turning to template is inversely proportional to the factor for its folding, which is F _SFR for RNA and F _SFD for DNA – wherein, F _SFR > F _SFD (and so DNA is easier to act as a template than RNA). The fidelity of the template-directed copying is associated with the probability of false base-pairing tolerated at each residue site when the substrates (monomers or oligomers) are attracted onto the template, which are here represented respectively by P _FPRR, P _FPRD, P _FPDD, and P _FPDR according to the type of the template as well as the type of the substrates. The replication of DNA is more accurate than that of RNA replication – i.e., P _FPDD < P _FPRR. See the text for details

Fig. 6

A scheme describing the routes concerning replication and transcription in the system. The chromosome is in a circular form: thick lines represent the sense chain, while thin lines represent the antisense chain. RNA is drawn in black, while DNA in red. Broad white arrows highlight the way in which the ribozymes (crescent-shapes) are created: the linear sense RNA, which arises from the spontaneous break of the sense chain of the RNA chromosome or partial copying of the antisense chain of the RNA or DNA chromosome, may be readily broken at sites (marked by short bands) between the linked genes (the so-called “self-cleaving” feature, see [15] for details). The routes which are led in the original pure RNA-based system can be easily identified at the left part, where no DNA (red line) is involved. When Nrr begins to take effect, “reverse transcription” may happen and give rise to the DNA chromosome (see the routes labeled by white triangles). When a thorough genetic takeover is completed, DNA’s replication (labeled by stars) and its transcription to the sense RNA chain (labeled by black triangles) would constitute the most significant information flow in the living system