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1.  Computational methods for Gene Orthology inference 
Briefings in Bioinformatics  2011;12(5):379-391.
Accurate inference of orthologous genes is a pre-requisite for most comparative genomics studies, and is also important for functional annotation of new genomes. Identification of orthologous gene sets typically involves phylogenetic tree analysis, heuristic algorithms based on sequence conservation, synteny analysis, or some combination of these approaches. The most direct tree-based methods typically rely on the comparison of an individual gene tree with a species tree. Once the two trees are accurately constructed, orthologs are straightforwardly identified by the definition of orthology as those homologs that are related by speciation, rather than gene duplication, at their most recent point of origin. Although ideal for the purpose of orthology identification in principle, phylogenetic trees are computationally expensive to construct for large numbers of genes and genomes, and they often contain errors, especially at large evolutionary distances. Moreover, in many organisms, in particular prokaryotes and viruses, evolution does not appear to have followed a simple ‘tree-like’ mode, which makes conventional tree reconciliation inapplicable. Other, heuristic methods identify probable orthologs as the closest homologous pairs or groups of genes in a set of organisms. These approaches are faster and easier to automate than tree-based methods, with efficient implementations provided by graph-theoretical algorithms enabling comparisons of thousands of genomes. Comparisons of these two approaches show that, despite conceptual differences, they produce similar sets of orthologs, especially at short evolutionary distances. Synteny also can aid in identification of orthologs. Often, tree-based, sequence similarity- and synteny-based approaches can be combined into flexible hybrid methods.
doi:10.1093/bib/bbr030
PMCID: PMC3178053  PMID: 21690100
homolog; ortholog; paralog; xenolog; orthologous groups; tree reconciliation; comparative genomics
2.  Comparison of Phylogenetic Trees and Search for a Central Trend in the “Forest of Life” 
Journal of Computational Biology  2011;18(7):917-924.
Abstract
The widespread exchange of genes among prokaryotes, known as horizontal gene transfer (HGT), is often considered to “uproot” the Tree of Life (TOL). Indeed, it is by now fully clear that genes in general possess different evolutionary histories. However, the possibility remains that the TOL concept can be reformulated and remain valid as a statistical central trend in the phylogenetic “Forest of Life” (FOL). This article describes a computational pipeline developed to chart the FOL by comparative analysis of thousands of phylogenetic trees. This analysis reveals a distinct, consistent phylogenetic signal that is particularly strong among the Nearly Universal Trees (NUTs), which correspond to genes represented in all or most of the analyzed organisms. Despite the substantial amount of apparent HGT seen even among the NUTs, these gene transfers appear to be distributed randomly and do not obscure the central tree-like trend.
doi:10.1089/cmb.2010.0185
PMCID: PMC3123530  PMID: 21457008
evolution; genomics
3.  Planctomycetes and eukaryotes: a case of analogy not homology 
Summary
Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla that are sometimes grouped together as the PVC superphylum of eubacteria. Some PVC species possess interesting attributes, in particular, internal membranes that superficially resemble eukaryotic endomembranes. Some biologists now claim that PVC bacteria are nucleus-bearing prokaryotes and that they are evolutionary intermediates in the transition from prokaryote to eukaryote. PVC prokaryotes do not possess a nucleus and are not intermediates in the prokaryote-to-eukaryote transition. All of the PVC traits that are currently cited as evidence for aspiring eukaryoticity are either analogous (the result of convergent evolution), not homologous, to eukaryotic traits; or else they are the result of lateral gene transfers. Here we summarize the evidence that shows why most of the purported similarities between the PVC bacteria and eukaryotes are analogous and the rest are consequence of lateral gene acquisition.
doi:10.1002/bies.201100045
PMCID: PMC3795523  PMID: 21858844
4.  Common Origins and Host-Dependent Diversity of Plant and Animal Viromes 
Current opinion in virology  2011;1(5):322-331.
Many viruses infecting animals and plants share common cores of homologous genes involved in the key processes of viral replication. In contrast, genes that mediate virus – host interactions including in many cases capsid protein genes are markedly different. There are three distinct scenarios for the origin of related viruses of plants and animals: i) evolution from a common ancestral virus predating the divergence of plants and animals; ii) horizontal transfer of viruses, for example, through insect vectors; iii) parallel origin from related genetic elements. We present evidence that each of these scenarios contributed, to a varying extent, to the evolution of different groups of viruses.
doi:10.1016/j.coviro.2011.09.007
PMCID: PMC3293486  PMID: 22408703
5.  Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli 
Virology  2011;417(2):334-342.
The F16L gene of vaccinia virus (VACV) is conserved in all chordopoxviruses except avipoxviruses. The crocodile poxvirus F16 protein ortholog has highly significant similarity to prokaryotic serine recombinases and contains all amino acids that comprise the catalytic site. In contrast, F16 orthologs encoded by other poxviruses show only marginally significant similarity to serine recombinases, lack essential amino acids of the active site and are most likely inactive derivatives of serine recombinases. Nevertheless, the conservation of F16L in non-avian poxviruses suggested an important function. However, a VACV mutant with the F16L gene knocked out replicated normally in dividing and quiescent cells. The F16 protein was synthesized early after infection and detected in virus cores. When expressed in infected or uninfected cells, F16 accumulated in nucleoli depending on the level of expression and confluency of cells. Evidence was obtained that F16 forms multimers, which might regulate concentration-dependent intracellular localization.
doi:10.1016/j.virol.2011.06.017
PMCID: PMC3163719  PMID: 21752417
poxvirus orthologs; poxvirus prokaryotic homologs; vaccinia virus replication; poxvirus recombinase
6.  Obituary: Walter Fitch and the orthology paradigm 
Briefings in Bioinformatics  2011;12(5):377-378.
doi:10.1093/bib/bbr058
PMCID: PMC3178060  PMID: 21949265
7.  Predictability of Evolutionary Trajectories in Fitness Landscapes 
PLoS Computational Biology  2011;7(12):e1002302.
Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.
Author Summary
Is evolution deterministic, hence predictable, or stochastic, that is unpredictable? What would happen if one could “replay the tape of evolution”: will the outcomes of evolution be completely different or is evolution so constrained that history will be repeated? Arguably, these questions are among the most intriguing and most difficult in evolutionary biology. In other words, the predictability of evolution depends on the fraction of the trajectories on fitness landscapes that are accessible for evolutionary exploration. Because direct experimental investigation of fitness landscapes is technically challenging, the available studies only explore a minuscule portion of the landscape for individual enzymes. We therefore sought to investigate the topography of fitness landscapes within the framework of a previously developed model of protein folding and evolution where fitness is equated with robustness to misfolding. We show that model-derived and experimental landscapes are significantly smoother than random landscapes and resemble moderately perturbed additive landscapes; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. Thus, the smoothness and substantial deficit of peaks in fitness landscapes of protein evolution could be fundamental consequences of the physics of protein folding.
doi:10.1371/journal.pcbi.1002302
PMCID: PMC3240586  PMID: 22194675
8.  Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs 
Genome Biology and Evolution  2011;3:1390-1404.
Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product.
doi:10.1093/gbe/evr116
PMCID: PMC3242500  PMID: 22071789
long noncoding RNA; ncRNA; RNA expression; genomic alignments; introns; RNA folding
9.  Divergence and Convergence in Enzyme Evolution* 
Comparative analysis of the sequences of enzymes encoded in a variety of prokaryotic and eukaryotic genomes reveals convergence and divergence at several levels. Functional convergence can be inferred when structurally distinct and hence non-homologous enzymes show the ability to catalyze the same biochemical reaction. In contrast, as a result of functional diversification, many structurally similar enzyme molecules act on substantially distinct substrates and catalyze diverse biochemical reactions. Here, we present updates on the ATP-grasp, alkaline phosphatase, cupin, HD hydrolase, and N-terminal nucleophile (Ntn) hydrolase enzyme superfamilies and discuss the patterns of sequence and structural conservation and diversity within these superfamilies. Typically, enzymes within a superfamily possess common sequence motifs and key active site residues, as well as (predicted) reaction mechanisms. These observations suggest that the strained conformation (the entatic state) of the active site, which is responsible for the substrate binding and formation of the transition complex, tends to be conserved within enzyme superfamilies. The subsequent fate of the transition complex is not necessarily conserved and depends on the details of the structures of the enzyme and the substrate. This variability of reaction outcomes limits the ability of sequence analysis to predict the exact enzymatic activities of newly sequenced gene products. Nevertheless, sequence-based (super)family assignments and generic functional predictions, even if imprecise, provide valuable leads for experimental studies and remain the best approach to the functional annotation of uncharacterized proteins from new genomes.
doi:10.1074/jbc.R111.241976
PMCID: PMC3249071  PMID: 22069324
Enzyme Catalysis; Enzyme Mechanisms; Enzyme Structure; Evolution; Phosphodiesterases; Convergence; Divergence
10.  Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems ▿†‡ 
Journal of Bacteriology  2011;193(21):6039-6056.
The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic “sinks” that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands.
doi:10.1128/JB.05535-11
PMCID: PMC3194920  PMID: 21908672
13.  Phylogenomics of prokaryotic ribosomal proteins 
Genome Biology  2011;12(Suppl 1):P30.
doi:10.1186/gb-2011-12-s1-p30
PMCID: PMC3439054
14.  A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes 
PLoS Computational Biology  2011;7(9):e1002150.
Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing.
Author Summary
In eukaryotes, protein-coding genes are interrupted by non-coding introns. The intron densities widely differ, from 6–7 introns per kilobase of coding sequence in vertebrates, some invertebrates and plants, to only a few introns across the entire genome in many unicellular forms. We applied a robust statistical methodology, Markov Chain Monte Carlo, to reconstruct the history of intron gain and loss throughout the evolution of eukaryotes using a set of 245 homologous genes from 99 genomes that represent the diversity of eukaryotes. Intron-rich ancestors were confidently inferred for each major eukaryotic group including 53% to 74% of the human intron density for the last eukaryotic common ancestor, and 120% to 130% of the human value for the last common ancestor of animals. Evolution of eukaryotic genes involved primarily intron loss, with substantial gain only at the bases of several major branches including plants and animals. Thus, the common ancestor of all extant eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. The line of descent from the last common ancestor to mammals was an uninterrupted intron-rich state that, given the error-prone splicing in intron-rich organisms, was conducive to the elaboration of functional alternative splicing.
doi:10.1371/journal.pcbi.1002150
PMCID: PMC3174169  PMID: 21935348
15.  Are There Laws of Genome Evolution? 
PLoS Computational Biology  2011;7(8):e1002173.
Research in quantitative evolutionary genomics and systems biology led to the discovery of several universal regularities connecting genomic and molecular phenomic variables. These universals include the log-normal distribution of the evolutionary rates of orthologous genes; the power law–like distributions of paralogous family size and node degree in various biological networks; the negative correlation between a gene's sequence evolution rate and expression level; and differential scaling of functional classes of genes with genome size. The universals of genome evolution can be accounted for by simple mathematical models similar to those used in statistical physics, such as the birth-death-innovation model. These models do not explicitly incorporate selection; therefore, the observed universal regularities do not appear to be shaped by selection but rather are emergent properties of gene ensembles. Although a complete physical theory of evolutionary biology is inconceivable, the universals of genome evolution might qualify as “laws of evolutionary genomics” in the same sense “law” is understood in modern physics.
doi:10.1371/journal.pcbi.1002173
PMCID: PMC3161903  PMID: 21901087
16.  Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems 
Biology Direct  2011;6:38.
Background
The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III).
Results
A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes.
Conclusions
Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution.
Open peer review
This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia), Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.
doi:10.1186/1745-6150-6-38
PMCID: PMC3150331  PMID: 21756346
17.  How stands the Tree of Life a century and a half after The Origin? 
Biology Direct  2011;6:32.
We examine the Tree of Life (TOL) as an evolutionary hypothesis and a heuristic. The original TOL hypothesis has failed but a new "statistical TOL hypothesis" is promising. The TOL heuristic usefully organizes data without positing fundamental evolutionary truth.
Reviewers
This article was reviewed by W. Ford Doolittle, Nicholas Galtier and Christophe Malaterre.
doi:10.1186/1745-6150-6-32
PMCID: PMC3158114  PMID: 21714936
18.  Viruses with More Than 1,000 Genes: Mamavirus, a New Acanthamoeba polyphaga mimivirus Strain, and Reannotation of Mimivirus Genes 
The genome sequence of the Mamavirus, a new Acanthamoeba polyphaga mimivirus strain, is reported. With 1,191,693 nt in length and 1,023 predicted protein-coding genes, the Mamavirus has the largest genome among the known viruses. The genomes of the Mamavirus and the previously described Mimivirus are highly similar in both the protein-coding genes and the intergenic regions. However, the Mamavirus contains an extra 5′-terminal segment that encompasses primarily disrupted duplicates of genes present elsewhere in the genome. The Mamavirus also has several unique genes including a small regulatory polyA polymerase subunit that is shared with poxviruses. Detailed analysis of the protein sequences of the two Mimiviruses led to a substantial amendment of the functional annotation of the viral genomes.
doi:10.1093/gbe/evr048
PMCID: PMC3163472  PMID: 21705471
Mimivirus; viral genome; nucleocytoplasmic large DNA viruses
19.  A late origin of the extant eukaryotic diversity: divergence time estimates using rare genomic changes 
Biology Direct  2011;6:26.
Background
Accurate estimation of the divergence time of the extant eukaryotes is a fundamentally important but extremely difficult problem owing primarily to gross violations of the molecular clock at long evolutionary distances and the lack of appropriate calibration points close to the date of interest. These difficulties are intrinsic to the dating of ancient divergence events and are reflected in the large discrepancies between estimates obtained with different approaches. Estimates of the age of Last Eukaryotic Common Ancestor (LECA) vary approximately twofold, from ~1,100 million years ago (Mya) to ~2,300 Mya.
Results
We applied the genome-wide analysis of rare genomic changes associated with conserved amino acids (RGC_CAs) and used several independent techniques to obtain date estimates for the divergence of the major lineages of eukaryotes with calibration intervals for insects, land plants and vertebrates. The results suggest an early divergence of monocot and dicot plants, approximately 340 Mya, raising the possibility of plant-insect coevolution. The divergence of bilaterian animal phyla is estimated at ~400-700 Mya, a range of dates that is consistent with cladogenesis immediately preceding the Cambrian explosion. The origin of opisthokonts (the supergroup of eukaryotes that includes metazoa and fungi) is estimated at ~700-1,000 Mya, and the age of LECA at ~1,000-1,300 Mya. We separately analyzed the red algal calibration interval which is based on single fossil. This analysis produced time estimates that were systematically older compared to the other estimates. Nevertheless, the majority of the estimates for the age of the LECA using the red algal data fell within the 1,200-1,400 Mya interval.
Conclusion
The inference of a "young LECA" is compatible with the latest of previously estimated dates and has substantial biological implications. If these estimates are valid, the approximately 1 to 1.4 billion years of evolution of eukaryotes that is open to comparative-genomic study probably was preceded by hundreds of millions years of evolution that might have included extinct diversity inaccessible to comparative approaches.
Reviewers
This article was reviewed by William Martin, Herve Philippe (nominated by I. King Jordan), and Romain Derelle.
doi:10.1186/1745-6150-6-26
PMCID: PMC3125394  PMID: 21595937
bilateria; opisthokonts; angiosperms; last eukaryotic common ancestor; molecular dating
20.  Structure and Activity of a Novel Archaeal β-CASP Protein with N-Terminal KH Domains 
Structure(London, England:1993)  2011;19(5):622-632.
Summary
MTH1203, a β-CASP metallo-β-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-β-lactamase nuclease and the β-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3′ ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome.
Graphical Abstract
Highlights
► MTH1203 combines RNA-processing and binding domains, unique to archaea ► MTH1203 is a Zn-dependent β-CASP RNase that functions as a dimer ► The MBL domain of MTH1203 binds U-rich sequences with a Kd in the micromolar range ► We propose MTH1203 acts with the proteasome degrading mRNAs of aberrant proteins
doi:10.1016/j.str.2011.03.002
PMCID: PMC3095777  PMID: 21565697
21.  On the Origin of DNA Genomes: Evolution of the Division of Labor between Template and Catalyst in Model Replicator Systems 
PLoS Computational Biology  2011;7(3):e1002024.
The division of labor between template and catalyst is a fundamental property of all living systems: DNA stores genetic information whereas proteins function as catalysts. The RNA world hypothesis, however, posits that, at the earlier stages of evolution, RNA acted as both template and catalyst. Why would such division of labor evolve in the RNA world? We investigated the evolution of DNA-like molecules, i.e. molecules that can function only as template, in minimal computational models of RNA replicator systems. In the models, RNA can function as both template-directed polymerase and template, whereas DNA can function only as template. Two classes of models were explored. In the surface models, replicators are attached to surfaces with finite diffusion. In the compartment models, replicators are compartmentalized by vesicle-like boundaries. Both models displayed the evolution of DNA and the ensuing division of labor between templates and catalysts. In the surface model, DNA provides the advantage of greater resistance against parasitic templates. However, this advantage is at least partially offset by the disadvantage of slower multiplication due to the increased complexity of the replication cycle. In the compartment model, DNA can significantly delay the intra-compartment evolution of RNA towards catalytic deterioration. These results are explained in terms of the trade-off between template and catalyst that is inherent in RNA-only replication cycles: DNA releases RNA from this trade-off by making it unnecessary for RNA to serve as template and so rendering the system more resistant against evolving parasitism. Our analysis of these simple models suggests that the lack of catalytic activity in DNA by itself can generate a sufficient selective advantage for RNA replicator systems to produce DNA. Given the widespread notion that DNA evolved owing to its superior chemical properties as a template, this study offers a novel insight into the evolutionary origin of DNA.
Author Summary
At the core of all biological systems lies the division of labor between the storage of genetic information and its phenotypic implementation, in other words, the functional differentiation between templates (DNA) and catalysts (proteins). This fundamental property of life is believed to have been absent at the earliest stages of evolution. The RNA world hypothesis, the most realistic current scenario for the origin of life, posits that, in primordial replicating systems, RNA functioned both as template and as catalyst. How would such division of labor emerge through Darwinian evolution? We investigated the evolution of DNA-like molecules in minimal computational models of RNA replicator systems. Two models were considered: one where molecules are adsorbed on surfaces and another one where molecules are compartmentalized by dividing cellular boundaries. Both models exhibit the evolution of DNA and the ensuing division of labor, revealing the simple governing principle of these processes: DNA releases RNA from the trade-off between template and catalyst that is inevitable in the RNA world and thereby enhances the system's resistance against parasitic templates. Hence, this study offers a novel insight into the evolutionary origin of the division of labor between templates and catalysts in the RNA world.
doi:10.1371/journal.pcbi.1002024
PMCID: PMC3063752  PMID: 21455287

Results 1-21 (21)