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Evolution of the division of labor between genes and enzymes in the RNA world.

Boza G, Szilágyi A, Kun Á, Santos M, Szathmáry E - PLoS Comput. Biol. (2014)

Bottom Line: Enzymatic activities of the two modeled ribozymes are in trade-off with their replication rates, and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes.Although some asymmetry between gene and enzymatic strands could have evolved even in earlier, surface-bound systems, the shown mechanism in protocells seems inevitable and under strong positive selection.This could have preadapted the genetic system for transcription after the subsequent origin of chromosomes and DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Systematics, Ecology and Theoretical Biology, Institute of Biology, Eötvös Loránd University, Budapest, Hungary; MTA-ELTE-MTMT Ecology Research Group, Budapest, Hungary.

ABSTRACT
The RNA world is a very likely interim stage of the evolution after the first replicators and before the advent of the genetic code and translated proteins. Ribozymes are known to be able to catalyze many reaction types, including cofactor-aided metabolic transformations. In a metabolically complex RNA world, early division of labor between genes and enzymes could have evolved, where the ribozymes would have been transcribed from the genes more often than the other way round, benefiting the encapsulating cells through this dosage effect. Here we show, by computer simulations of protocells harboring unlinked RNA replicators, that the origin of replicational asymmetry producing more ribozymes from a gene template than gene strands from a ribozyme template is feasible and robust. Enzymatic activities of the two modeled ribozymes are in trade-off with their replication rates, and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes. The degree of trade-off is shown to have the strongest effect in favor of the division of labor. Although some asymmetry between gene and enzymatic strands could have evolved even in earlier, surface-bound systems, the shown mechanism in protocells seems inevitable and under strong positive selection. This could have preadapted the genetic system for transcription after the subsequent origin of chromosomes and DNA.

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Characteristics of secondary structures of complementary strands.The characteristics of minimum free energy secondary structures are measured on a sample of 107 randomly generated sequences of length 50. In case of complementary strands, the complementary sequences of the randomly generated strands are also analyzed. (A) Complementary strands have higher full tree edit distance between them (red bars) than random sequence pairs (black bars). (B) Energy difference between members of pairs of complementary, folded strands. Around tree edit distance 30 most complementary, folded structures have negligible energy difference, but a decreasing proportion of pairs show a difference of up to 40 kcal. (C) Example of a complementary pair of strands in which one of the strands does not have a structure, while the other has a rich structure. The difference of their minimum free energies is (6.6 kcal). (D) Example of a complementary pair of strands in which the two strands have very different (tree edit distance 68) but still rich structures. The difference of their minimum free energies is (7.0 kcal).
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pcbi-1003936-g006: Characteristics of secondary structures of complementary strands.The characteristics of minimum free energy secondary structures are measured on a sample of 107 randomly generated sequences of length 50. In case of complementary strands, the complementary sequences of the randomly generated strands are also analyzed. (A) Complementary strands have higher full tree edit distance between them (red bars) than random sequence pairs (black bars). (B) Energy difference between members of pairs of complementary, folded strands. Around tree edit distance 30 most complementary, folded structures have negligible energy difference, but a decreasing proportion of pairs show a difference of up to 40 kcal. (C) Example of a complementary pair of strands in which one of the strands does not have a structure, while the other has a rich structure. The difference of their minimum free energies is (6.6 kcal). (D) Example of a complementary pair of strands in which the two strands have very different (tree edit distance 68) but still rich structures. The difference of their minimum free energies is (7.0 kcal).

Mentions: We investigated the evolution of division labor between enzymatic and genetic strands based on the implicit assumption that minus and plus strands can have very different secondary structures. This indeed proves to be the case: on a sample of 10 million sequences, the distances between the secondary structures of minus and plus strands are slightly higher than those between pairs of randomly generated sequences (Figure 6A). Furthermore, there is asymmetry in the complexity of secondary structures (Figure 6A, C, D); and the difference between the free energies of folding can reach levels up to 20 kcal/mol (Figure 6B). Thus, there is a fraction of complementary, folded strand pairs for which one member is more readily opened by a replicase than the other, due to the looser structure of the former (Figure 6C). Here we have only considered the minimum free energy (MFE) structures of the RNAs. It is known that there are suboptimal structures that could be quite close energetically to the MFE structure [25], and thus provide additional ways in which the two strands can be different (albeit evolution can lead to well-defined structures with little ambiguity in their energetically close sub-optimal structures [26]). Co-folding of the RNA with smaller RNAs can further increase the structural diversity of RNAs [27], again possibly promoting functional diversification of the strands. Our conservative estimate of structural difference is sufficient for strand separation, and incorporation of further mechanisms can further foster the effect demonstrated above.


Evolution of the division of labor between genes and enzymes in the RNA world.

Boza G, Szilágyi A, Kun Á, Santos M, Szathmáry E - PLoS Comput. Biol. (2014)

Characteristics of secondary structures of complementary strands.The characteristics of minimum free energy secondary structures are measured on a sample of 107 randomly generated sequences of length 50. In case of complementary strands, the complementary sequences of the randomly generated strands are also analyzed. (A) Complementary strands have higher full tree edit distance between them (red bars) than random sequence pairs (black bars). (B) Energy difference between members of pairs of complementary, folded strands. Around tree edit distance 30 most complementary, folded structures have negligible energy difference, but a decreasing proportion of pairs show a difference of up to 40 kcal. (C) Example of a complementary pair of strands in which one of the strands does not have a structure, while the other has a rich structure. The difference of their minimum free energies is (6.6 kcal). (D) Example of a complementary pair of strands in which the two strands have very different (tree edit distance 68) but still rich structures. The difference of their minimum free energies is (7.0 kcal).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256009&req=5

pcbi-1003936-g006: Characteristics of secondary structures of complementary strands.The characteristics of minimum free energy secondary structures are measured on a sample of 107 randomly generated sequences of length 50. In case of complementary strands, the complementary sequences of the randomly generated strands are also analyzed. (A) Complementary strands have higher full tree edit distance between them (red bars) than random sequence pairs (black bars). (B) Energy difference between members of pairs of complementary, folded strands. Around tree edit distance 30 most complementary, folded structures have negligible energy difference, but a decreasing proportion of pairs show a difference of up to 40 kcal. (C) Example of a complementary pair of strands in which one of the strands does not have a structure, while the other has a rich structure. The difference of their minimum free energies is (6.6 kcal). (D) Example of a complementary pair of strands in which the two strands have very different (tree edit distance 68) but still rich structures. The difference of their minimum free energies is (7.0 kcal).
Mentions: We investigated the evolution of division labor between enzymatic and genetic strands based on the implicit assumption that minus and plus strands can have very different secondary structures. This indeed proves to be the case: on a sample of 10 million sequences, the distances between the secondary structures of minus and plus strands are slightly higher than those between pairs of randomly generated sequences (Figure 6A). Furthermore, there is asymmetry in the complexity of secondary structures (Figure 6A, C, D); and the difference between the free energies of folding can reach levels up to 20 kcal/mol (Figure 6B). Thus, there is a fraction of complementary, folded strand pairs for which one member is more readily opened by a replicase than the other, due to the looser structure of the former (Figure 6C). Here we have only considered the minimum free energy (MFE) structures of the RNAs. It is known that there are suboptimal structures that could be quite close energetically to the MFE structure [25], and thus provide additional ways in which the two strands can be different (albeit evolution can lead to well-defined structures with little ambiguity in their energetically close sub-optimal structures [26]). Co-folding of the RNA with smaller RNAs can further increase the structural diversity of RNAs [27], again possibly promoting functional diversification of the strands. Our conservative estimate of structural difference is sufficient for strand separation, and incorporation of further mechanisms can further foster the effect demonstrated above.

Bottom Line: Enzymatic activities of the two modeled ribozymes are in trade-off with their replication rates, and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes.Although some asymmetry between gene and enzymatic strands could have evolved even in earlier, surface-bound systems, the shown mechanism in protocells seems inevitable and under strong positive selection.This could have preadapted the genetic system for transcription after the subsequent origin of chromosomes and DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Systematics, Ecology and Theoretical Biology, Institute of Biology, Eötvös Loránd University, Budapest, Hungary; MTA-ELTE-MTMT Ecology Research Group, Budapest, Hungary.

ABSTRACT
The RNA world is a very likely interim stage of the evolution after the first replicators and before the advent of the genetic code and translated proteins. Ribozymes are known to be able to catalyze many reaction types, including cofactor-aided metabolic transformations. In a metabolically complex RNA world, early division of labor between genes and enzymes could have evolved, where the ribozymes would have been transcribed from the genes more often than the other way round, benefiting the encapsulating cells through this dosage effect. Here we show, by computer simulations of protocells harboring unlinked RNA replicators, that the origin of replicational asymmetry producing more ribozymes from a gene template than gene strands from a ribozyme template is feasible and robust. Enzymatic activities of the two modeled ribozymes are in trade-off with their replication rates, and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes. The degree of trade-off is shown to have the strongest effect in favor of the division of labor. Although some asymmetry between gene and enzymatic strands could have evolved even in earlier, surface-bound systems, the shown mechanism in protocells seems inevitable and under strong positive selection. This could have preadapted the genetic system for transcription after the subsequent origin of chromosomes and DNA.

Show MeSH
Related in: MedlinePlus