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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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Schematic representation of the main reactions and components of vesicles with complementary replicating strands.Vesicles are composed of two types of macromolecules (type 1 as red, and type 2 as blue), and with two strand types (plus () strands with light, and minus () strands with dark shading). The minus () strands (molecules colored dark red) serve both as enzymes (enzymatic activity indicated with asterisk) for producing monomers (molecule colored green) from source material, and as templates for producing plus () strands (molecules colored orange). The monomers are used as the building blocks (green arrow) for the productions of replicators (replication complexes are indicated in curly brackets). The plus strand only serves as template for producing minus strands. For molecule type 2, the metabolic and replication processes are similar to those of molecule type 1 described above, except that the minus () strand catalyzes a different chemical reaction.
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pcbi-1003936-g001: Schematic representation of the main reactions and components of vesicles with complementary replicating strands.Vesicles are composed of two types of macromolecules (type 1 as red, and type 2 as blue), and with two strand types (plus () strands with light, and minus () strands with dark shading). The minus () strands (molecules colored dark red) serve both as enzymes (enzymatic activity indicated with asterisk) for producing monomers (molecule colored green) from source material, and as templates for producing plus () strands (molecules colored orange). The monomers are used as the building blocks (green arrow) for the productions of replicators (replication complexes are indicated in curly brackets). The plus strand only serves as template for producing minus strands. For molecule type 2, the metabolic and replication processes are similar to those of molecule type 1 described above, except that the minus () strand catalyzes a different chemical reaction.

Mentions: Here we address the problem of RNA strand asymmetry in the context of metabolically active ribozymes encapsulated in reproducing protocells, relying on the stochastic corrector model [12], [17] for the basic dynamics. There are two different ribozymes () that are assumed to be essential for protocell growth and reproduction (Figure 1). In contrast to previous treatments plus () and minus () strands are explicitly considered. For simplicity we assume that only minus strands are enzymatically active. All templates grow stochastically within each protocell, and protocells also grow and divide stochastically. There is selection at two levels: faster replicating templates within protocells have an advantage, but protocells with a balanced and adequately abundant ribozyme composition are favored [17]. Although we assume their existence, we do not explicitly model replicase molecules, except that a limited number of templates can be replicated at the same time. Their effect is assumed to allow for copying of plus strand from minus strands and vice versa, including neat strand separation (which is still an unsolved problem in the origin of life studies [18]). It is assumed that minus strands being copied cannot perform enzymatic function at the same time, due to the opening of the catalytic sites. The two ribozymes are assumed to contribute to the production of the nucleotide monomers of the RNAs. One of the ribozymes (type 1) transforms a source material available in the environment to intermediate , which in turn is transformed by the other ribozyme (type 2) to the monomer . The monomer is then consumed to build up the four different kinds of strands present in the vesicle. Concrete examples of similar ribozymes that could have helped sustain the RNA world have been successfully selected in vitro[19], including nucleoside synthesis, phosphorylation of nucleosides, activation of nucleotides, and processive RNA primer extension. The rates of these reactions are determined by the catalytic activities of the ribozymes. The enzymatic activities of the ribozymes are in trade-off with their replication rates (e.g., active ribozymes are more difficult to unfold due to a denser structure and substrate binding), and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes. Both higher and lower relative replication rates of the minus strands are allowed to evolve. The traits can change at each replication due to mutations. When the within-vesicle concentration of RNAs reaches a critical level the vesicle splits into two and its content is divided randomly, without replacement, between the two resultant daughter vesicles. See Methods for details and Table 1 for parameters and their values used throughout this study.


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)

Schematic representation of the main reactions and components of vesicles with complementary replicating strands.Vesicles are composed of two types of macromolecules (type 1 as red, and type 2 as blue), and with two strand types (plus () strands with light, and minus () strands with dark shading). The minus () strands (molecules colored dark red) serve both as enzymes (enzymatic activity indicated with asterisk) for producing monomers (molecule colored green) from source material, and as templates for producing plus () strands (molecules colored orange). The monomers are used as the building blocks (green arrow) for the productions of replicators (replication complexes are indicated in curly brackets). The plus strand only serves as template for producing minus strands. For molecule type 2, the metabolic and replication processes are similar to those of molecule type 1 described above, except that the minus () strand catalyzes a different chemical reaction.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003936-g001: Schematic representation of the main reactions and components of vesicles with complementary replicating strands.Vesicles are composed of two types of macromolecules (type 1 as red, and type 2 as blue), and with two strand types (plus () strands with light, and minus () strands with dark shading). The minus () strands (molecules colored dark red) serve both as enzymes (enzymatic activity indicated with asterisk) for producing monomers (molecule colored green) from source material, and as templates for producing plus () strands (molecules colored orange). The monomers are used as the building blocks (green arrow) for the productions of replicators (replication complexes are indicated in curly brackets). The plus strand only serves as template for producing minus strands. For molecule type 2, the metabolic and replication processes are similar to those of molecule type 1 described above, except that the minus () strand catalyzes a different chemical reaction.
Mentions: Here we address the problem of RNA strand asymmetry in the context of metabolically active ribozymes encapsulated in reproducing protocells, relying on the stochastic corrector model [12], [17] for the basic dynamics. There are two different ribozymes () that are assumed to be essential for protocell growth and reproduction (Figure 1). In contrast to previous treatments plus () and minus () strands are explicitly considered. For simplicity we assume that only minus strands are enzymatically active. All templates grow stochastically within each protocell, and protocells also grow and divide stochastically. There is selection at two levels: faster replicating templates within protocells have an advantage, but protocells with a balanced and adequately abundant ribozyme composition are favored [17]. Although we assume their existence, we do not explicitly model replicase molecules, except that a limited number of templates can be replicated at the same time. Their effect is assumed to allow for copying of plus strand from minus strands and vice versa, including neat strand separation (which is still an unsolved problem in the origin of life studies [18]). It is assumed that minus strands being copied cannot perform enzymatic function at the same time, due to the opening of the catalytic sites. The two ribozymes are assumed to contribute to the production of the nucleotide monomers of the RNAs. One of the ribozymes (type 1) transforms a source material available in the environment to intermediate , which in turn is transformed by the other ribozyme (type 2) to the monomer . The monomer is then consumed to build up the four different kinds of strands present in the vesicle. Concrete examples of similar ribozymes that could have helped sustain the RNA world have been successfully selected in vitro[19], including nucleoside synthesis, phosphorylation of nucleosides, activation of nucleotides, and processive RNA primer extension. The rates of these reactions are determined by the catalytic activities of the ribozymes. The enzymatic activities of the ribozymes are in trade-off with their replication rates (e.g., active ribozymes are more difficult to unfold due to a denser structure and substrate binding), and the relative replication rates compared to those of complementary strands are evolvable traits of the ribozymes. Both higher and lower relative replication rates of the minus strands are allowed to evolve. The traits can change at each replication due to mutations. When the within-vesicle concentration of RNAs reaches a critical level the vesicle splits into two and its content is divided randomly, without replacement, between the two resultant daughter vesicles. See Methods for details and Table 1 for parameters and their values used throughout this study.

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