Journal of Molecular Evolution (J Mol Evol)

Publisher: Springer Verlag

Journal description

The Journal covers experimental and theoretical work aimed at deciphering features of molecular evolution and the processes bearing on these features from the initial formation of macromolecular systems onward. Topics addressed in the Journal include the evolution of informational macromolecules and their relation to more complex levels of biological organization up to populations and taxa. This coverage accommodates well such subfields as comparative structural and functional genomics population genetics the molecular evolution of development the evolution of gene regulation and gene interaction networks and in vitro evolution of DNA and RNA.

Current impact factor: 1.68

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 1.68
2013 Impact Factor 1.863
2012 Impact Factor 2.145
2011 Impact Factor 2.274
2010 Impact Factor 2.311
2009 Impact Factor 2.323
2008 Impact Factor 2.762
2007 Impact Factor 3.234
2006 Impact Factor 2.767
2005 Impact Factor 2.703
2004 Impact Factor 2.751
2003 Impact Factor 3.114
2002 Impact Factor 3.041
2001 Impact Factor 4.011
2000 Impact Factor 3.984
1999 Impact Factor 3.655
1998 Impact Factor 3.271
1997 Impact Factor 3.181
1996 Impact Factor 3.052
1995 Impact Factor 3.519
1994 Impact Factor 3.777
1993 Impact Factor 3.484
1992 Impact Factor 3.15

Impact factor over time

Impact factor

Additional details

5-year impact 1.95
Cited half-life >10.0
Immediacy index 0.37
Eigenfactor 0.00
Article influence 0.74
Website Journal of Molecular Evolution website
Other titles Journal of molecular evolution (Online), Molecular evolution, J mol evol
ISSN 1432-1432
OCLC 39983975
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

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    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: We report an investigation of the functional relationship between two independently selected RNA-cleaving DNAzymes, NaA43, and Ce13, through in vitro selection. The NaA43 DNAzyme was obtained through a combination of gel-based and column-based in vitro selection in the presence of Na(+) and reported to be highly selective for Na(+) over other metal ions. The Ce13 DNAzyme was isolated via a gel-based method in the presence of Ce(4+) and found to be active with trivalent lanthanides, Y(3+) and Pb(2+). Despite completely different activities reported for the two DNAzymes, they share a high level of sequence similarity (~60 % sequence identity). In this work, we systematically analyzed the activity of both DNAzymes to elucidate their potential functional relationship. We found that Na(+) is an obligate cofactor of the Ce13 DNAzyme and lanthanides cannot initiate the cleavage reaction in the absence of Na(+). Hence, we conclude that the Ce13 DNAzyme is a variant of the NaA43 DNAzyme that catalyzes reaction in the presence Na(+) and also utilizes lanthanides in a potentially allosteric manner. These results have identified a new DNAzyme motif that is not only remarkably Na(+)-specific, but also allows for design of novel allosteric DNAzymes for different biotechnological applications.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9715-7
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    ABSTRACT: Here, we report a fluorescent probe based on a macrocyclic peptide scaffold that specifically stains EpCAM-expressing MCF7 cells. The 14-mer macrocyclic peptide binding to the extracellular domain of EpCAM with a dissociation constant in the low nM range (1.7 nM) was discovered using the random non-standard peptide-integrated discovery system. Notably, this probe containing a fluorescence tag is less than 3000 Da in total and able to visualize nearly every live cell under high cell-density conditions, which was not achieved by the conventional mAb staining method. This suggests that the molecular probe based on the compact macrocyclic scaffold has great potentials as an imaging tool for the EpCAM biomarker as well as a delivery vehicle for drug conjugates.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9710-z
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    ABSTRACT: Aptamers of high affinity and specificity have a wide range of analytic and clinical applications. Selection of DNA or RNA aptamer molecules usually involves systematic evolution of ligands via exponential enrichment (SELEX), in which a random DNA or RNA library is incubated with a target molecule, and the oligonucleotides that bind the target are then separated from the nonbinders, PCR amplified, and used as refined libraries in the next round of selection. Conventional SELEX methodologies require the use of purified target molecules and their immobilization onto a solid support. However, purified targets from cells are not always available, and fixing the target to a support may alter its conformation. To overcome these problems, we have developed a SELEX technique using live bacterial cells in suspension as targets, for selecting DNA aptamers specific to cell-surface molecules. Through the selection of aptamers binding to Lactobacillus acidophilus and Streptococcus pyogenes, we report here optimization of this technique and show how varying selection conditions impact the characteristics of resultant aptamer pools, including the binding affinity, selectivity, and the secondary structures. We found that the use of larger starting library sequence diversity, gel purification of the subsequent pools, and the introduction of counter-selection resulted in a more efficient SELEX process and more selective aptamers. A SELEX protocol with lower starting sequence diversity, the use of heat denaturation, and the absence of counter-selection still resulted in high-affinity aptamer sequences specific to the target cell types; however, the SELEX process was inefficient, requiring 20 rounds, and the aptamers were not specific to the strain of the bacterial cells. Strikingly, two different SELEX methodologies yielded the same sequence that bound strongly to the target S. pyogenes cells, suggesting the robustness of the bacterial cell-SELEX technique.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9711-y
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    ABSTRACT: Some mutations in gene coding regions exchange one synonymous codon for another, and thus do not alter the amino acid sequence of the encoded protein. Even though they are often called 'silent,' these mutations may exhibit a plethora of effects on the living cell. Therefore, they are often selected during evolution, causing synonymous codon usage biases in genomes. Comparative analyses of bacterial, archaeal, fungal, and human cancer genomes have found many links between a gene's biological role and the accrual of synonymous mutations during evolution. In particular, highly expressed genes in certain functional categories are enriched with optimal codons, which are decoded by the abundant tRNAs, thus enhancing the speed and accuracy of the translating ribosome. The set of genes exhibiting codon adaptation differs between genomes, and these differences show robust associations to organismal phenotypes. In addition to selection for translation efficiency, other distinct codon bias patterns have been found in: amino acid starvation genes, cyclically expressed genes, tissue-specific genes in animals and plants, oxidative stress response genes, cellular differentiation genes, and oncogenes. In addition, genomes of organisms harboring tRNA modifications exhibit particular codon preferences. The evolutionary trace of codon bias patterns across orthologous genes may be examined to learn about a gene's relevance to various phenotypes, or, more generally, its function in the cell.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9714-8
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    ABSTRACT: We have previously shown that through test-tube molecular evolution, an arbitrarily chosen noncatalytic DNA sequence can be evolved into a catalytic DNA (DNAzyme) with significant RNA-cleaving activity. In this study, we aim to address the question of whether the catalytic activity of such a DNAzyme can be further optimized using in vitro selection. Several cycles of selective enrichment starting with a partially randomized DNA library have resulted in the isolation of many sequence variations that show notably improved catalytic activity. Bioinformatic analysis and activity examination of several DNAzyme-substrate constructs have led to two interesting findings about sequence mutations and the secondary structure of this DNAzyme: (1) three crucial mutations have transformed the DNAzyme into 8-17, a DNAzyme that has been discovered in multiple previous in vitro selection experiments, and (2) other mutations have allowed this special 8-17 variant to make structural fine-tuning in order to cleave an arbitrarily chosen RNA-containing substrate with a defined sequence. Our study not only showcases the combined power of directed molecular evolution and in vitro selection techniques in turning a noncatalytic nucleic acid sequence into an efficient enzyme, but it also raises the question of whether mother nature has used a similar approach to evolve natural enzymes.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9712-x
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    ABSTRACT: Emergence of the very first RNA or RNA-like oligomers from simple nucleotide precursors is one of the most intriguing questions of the origin of life research. In the current paper, we analyse the mechanism of four non-enzymatic template-free scenarios suggested for the oligomerization of chemically non-modified cyclic and acyclic nucleotides in the literature. We show that amines may have a twofold role in these syntheses: due to their high affinity to bind protons they may activate the phosphorus of the phosphate group via proton transfer reactions, or indirectly they may serve as charge compensating species and influence the self-assembling of nucleotides to supramolecular architectures compatible with the oligomerization reactions. Effect of cations and pH on the reactions is also discussed.
    Journal of Molecular Evolution 11/2015; DOI:10.1007/s00239-015-9709-5
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    ABSTRACT: In vitro selection or SELEX has allowed for the identification of functional nucleic acids (FNAs) that can potentially mimic and replace protein enzymes. These FNAs likely interact with cofactors, just like enzymes bind cofactors in their active sites. Investigating how FNA binding affects cofactor properties is important for understanding how an active site is formed and for developing useful enzyme mimics. Oxidoreductase enzymes contain cofactors in their active sites that allow the enzymes to do redox chemistry. In certain applications, these redox cofactors act as electron-transfer shuttles that transport electrons between the enzymes' active sites and electrode surfaces. Three redox cofactors commonly found in oxidoreductases are flavin adenine dinucleotide, nicotinamide adenine dinucleotide (NAD(+)), and pyrroloquinoline quinone (PQQ). We are interested in investigating how DNA aptamers that bind these cofactors influence the cofactors' redox abilities and if these aptamer-cofactor complexes could serve as redox catalysts. We employed cyclic voltammetry and amperometry to study the electrochemical properties of NAD(+) and PQQ when bound to DNA aptamers. Our results suggest that the aptamers provide a stable environment for the cofactor to participate in redox reactions, although enhanced redox activity was not observed. This work provides a foundation for the development of new FNAs capable of redox activity.
    Journal of Molecular Evolution 10/2015; DOI:10.1007/s00239-015-9707-7

  • Journal of Molecular Evolution 10/2015; DOI:10.1007/s00239-015-9705-9

  • Journal of Molecular Evolution 10/2015; DOI:10.1007/s00239-015-9706-8
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    ABSTRACT: The leadzyme refers to a small ribozyme that cleaves a RNA substrate in the presence of Pb(2+). In an optimized form, the enzyme strand contains only two unpaired nucleotides. Most RNA-cleaving DNAzymes are much longer. Two classical Pb(2+)-dependent DNAzymes, 8-17 and GR5, both contain around 15 nucleotides in the enzyme loop. This is also the size of most RNA-cleaving DNAzymes that use other metal ions for their activity. Such large enzyme loops make spectroscopic characterization difficult and so far no high-resolution structural information is available for active DNAzymes. The goal of this work is to search for DNAzymes with smaller enzyme loops. A simple replacement of the ribonucleotides in the leadzyme by deoxyribonucleotides failed to produce an active enzyme. A Pb(2+)-dependent in vitro selection combined with deep sequencing was then performed. After sequence alignment and DNA folding, a new DNAzyme named PbE22 was identified, which contains only 5 nucleotides in the enzyme catalytic loop. The biochemical characteristics of PbE22 were compared with those of the leadzyme and the two classical Pb(2+)-dependent DNAzymes. The rate of PbE22 rises with increase in Pb(2+) concentration, being 1.7 h(-1) in the presence of 100 μM Pb(2+) and reaching 3.5 h(-1) at 500 µM Pb(2+). The log of PbE22 rate rises linearly in a pH-dependent fashion (20 µM Pb(2+)) with a slope of 0.74. In addition, many other abundant sequences in the final library were studied. These sequences are quite varied in length and nucleotide composition, but some contain a few conserved nucleotides consistent with the GR5 structure. Interestingly, some sequences are active with Pb(2+) but none of them were active with even 50 mM Mg(2+), which is reminiscent of the difference between the GR5 and 8-17 DNAzymes.
    Journal of Molecular Evolution 10/2015; DOI:10.1007/s00239-015-9702-z
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    ABSTRACT: Angiosperm mitochondrial genes appear to have very low mutation rates, while non-gene regions expand, diverge, and rearrange quickly. One possible explanation for this disparity is that synonymous substitutions in plant mitochondrial genes are not truly neutral and selection keeps their occurrence low. If this were true, the explanation for the disparity in mutation rates in genes and non-genes needs to consider selection as well as mechanisms of DNA repair. Rps14 is co-transcribed with cob and rpl5 in most plant mitochondrial genomes, but in some genomes, rps14 has been duplicated to the nucleus leaving a pseudogene in the mitochondria. This provides an opportunity to compare neutral substitution rates in pseudogenes with synonymous substitution rates in the orthologs. Genes and pseudogenes of rps14 have been aligned among different species and the mutation rates have been calculated. Neutral substitution rates in pseudogenes and synonymous substitution rates in genes are significantly different, providing evidence that synonymous substitutions in plant mitochondrial genes are not completely neutral. The non-neutrality is not sufficient to completely explain the exceptionally low mutation rates in land plant mitochondrial genomes, but selective forces appear to play a small role.
    Journal of Molecular Evolution 10/2015; 81(3-4). DOI:10.1007/s00239-015-9704-x
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    ABSTRACT: Lampreys and hagfish are the earliest diverging of extant vertebrates and are obvious targets for investigating the origins of complex biochemical systems found in mammals. Currently, the simplest approach for such inquiries is to search for the presence of relevant genes in whole genome sequence (WGS) assemblies. Unhappily, in the past a high-quality complete genome sequence has not been available for either lampreys or hagfish, precluding the possibility of proving gene absence. Recently, improved but still incomplete genome assemblies for two species of lamprey have been posted, and, taken together with an extensive collection of short sequences in the NCBI trace archive, they have made it possible to make reliable counts for specific gene families. Particularly, a multi-source tactic has been used to study the lamprey blood clotting system with regard to the presence and absence of genes known to occur in higher vertebrates. As was suggested in earlier studies, lampreys lack genes for coagulation factors VIII and IX, both of which are critical for the "intrinsic" clotting system and responsible for hemophilia in humans. On the other hand, they have three each of genes for factors VII and X, participants in the "extrinsic" clotting system. The strategy of using raw trace sequence "reads" together with partial WGS assemblies for lampreys can be used in studies on the early evolution of other biochemical systems in vertebrates.
    Journal of Molecular Evolution 10/2015; 81(3). DOI:10.1007/s00239-015-9701-0
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    ABSTRACT: The widely acknowledged 'RNA world' theory pertains to how life might have chemically originated on early Earth. It presumes the existence of catalytic RNAs, which were also capable of storing and propagating genetic information. Substantial research has gone into understanding how enzyme-free reactions of nucleic acids might have led to the formation of such catalytic RNA polymers. However, most of these studies involved reactions that were performed in aqueous systems devoid of any "background" molecules. This scenario is not a true representation of the complex chemical environment that might have been prevalent on prebiotic Earth. In the present study, we analyzed the effect of co-solutes ("background" molecules) on the rate and accuracy of template-directed nonenzymatic replication of RNA, in a putative RNA world. Our results suggest that presence of co-solutes in the reaction affects the addition of purine monomers across their cognate template base. Reduction in the rate of these 'fast' cognate addition reactions resulted in an apparent increase in the frequency of mismatches in the presence of co-solutes. However, reactions that involved the addition of a mismatched base were not notably affected. Such a scenario could have led to an accrual of mutations during the propagation of functional sequences on early Earth, unless the relevant sequences were separated from the bulk reaction milieu by some limiting boundary structure (e.g., a membrane). In general, our results suggest that the presence of co-solutes could have affected certain prebiotic reaction rates to a larger extent than others. Even modest changes in nonenzymatic replication reaction rates could have eventually resulted in the accumulation of greater variation in RNA sequences over prolonged time periods. It, therefore, is pertinent to account for the chemical complexity intrinsic to prebiotic environments while studying relevant nonenzymatic reactions.
    Journal of Molecular Evolution 10/2015; 81(3). DOI:10.1007/s00239-015-9700-1
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    ABSTRACT: Deoxyribozymes (DNA enzymes) have been developed for a growing variety of chemical reactions, including with peptide substrates. We recently described the first tyrosine kinase deoxyribozymes, which lacked the ability to discriminate among peptide substrates on the basis of the amino acids surrounding the tyrosine residue. Those deoxyribozymes were identified by in vitro selection using a DNA-anchored peptide substrate in which the residues neighboring tyrosine were all alanine. Here, we performed in vitro selection for tyrosine kinase activity using three peptide substrates in which the neighboring residues included a variety of side chains. For one of these three peptides, we found numerous deoxyribozymes that discriminate strongly in favor of phosphorylating tyrosine when the surrounding residues are specifically those used in the selection process. Three different short peptide sequence motifs of 2-4 amino acids were required for catalysis by three unique deoxyribozymes. For a second peptide substrate, the selection process led to one deoxyribozyme which exhibits partial discrimination among peptide sequences. These findings establish the feasibility of identifying DNA enzymes that catalyze sequence-selective tyrosine phosphorylation, which suggests the downstream practical utility of such deoxyribozymes. More broadly, this outcome reinforces the conclusion that nucleic acid catalysts can discriminate among peptide substrates in the context of biochemically relevant reactions.
    Journal of Molecular Evolution 09/2015; DOI:10.1007/s00239-015-9699-3