Special Issue "The Origins and Early Evolution of RNA"


A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Chemistry".

Deadline for manuscript submissions: closed (30 September 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Niles Lehman
Department of Chemistry, Portland State University, PO Box 751, Portland, OR 97207, USA
Website: http://www.pdx.edu/clas/profile/dr-niles-lehman
E-Mail: niles@pdx.edu
Phone: +1 503 725 8769
Interests: origins of life; RNA; ribozymes; recombination; prebiotic chemistry; systems chemistry, cooperation; in vitro evolution

Special Issue Information

Dear Colleagues,

The notion that molecular systems such as RNA can display a wide range of evolutionary processes in the absence of fully formed cellular life continues to gain support. Understanding how RNA can behave in an abiotic context is a key piece of our picture of how life developed and expanded on the Earth, and by proxy, elsewhere. We can study how RNA behaves in this regard through a combination of in vivo work (with small regulatory RNAs and larger catalytic RNAs alike), experimental work in the laboratory, and through powerful analytical and simulation studies. These efforts will not only grant us a better sense of the early stages of life on this planet but also of how RNA evolved to play a central role in contemporary metabolism. Many key ideas of primitive RNA functionality were developed in the 1970s and 1980s before we had either the experimental systems in place to fully explore these concepts or the appreciation of the extent to which RNAs were important to the cell. In this special issue, some of the recent discoveries and advances in RNA biology, biochemistry, and evolutionary biology are presented.

Prof. Dr. Niles Lehman
Guest Editor


Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


  • RNA
  • primitive genotypes
  • genetic networks
  • fitness landscapes
  • genetic takeover
  • early evolutionary processes
  • evolvability
  • robustness
  • error threshold
  • quasispecies
  • small RNA-directed gene regulation

Published Papers (7 papers)

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Displaying article 1-7
p. 1013-1025
Life 2014, 4(4), 1013-1025; doi:10.3390/life4041013
Received: 23 October 2014; in revised form: 27 November 2014 / Accepted: 11 December 2014 / Published: 16 December 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
p. 887-902
by , ,  and
Life 2014, 4(4), 887-902; doi:10.3390/life4040887
Received: 12 October 2014; in revised form: 1 December 2014 / Accepted: 2 December 2014 / Published: 11 December 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
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p. 800-818
Life 2014, 4(4), 800-818; doi:10.3390/life4040800
Received: 7 October 2014; in revised form: 11 November 2014 / Accepted: 12 November 2014 / Published: 24 November 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
p. 788-799
by ,  and
Life 2014, 4(4), 788-799; doi:10.3390/life4040788
Received: 30 September 2014; in revised form: 12 November 2014 / Accepted: 17 November 2014 / Published: 21 November 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
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p. 341-373
by , , , , ,  and
Life 2014, 4(3), 341-373; doi:10.3390/life4030341
Received: 29 April 2014; in revised form: 23 July 2014 / Accepted: 25 July 2014 / Published: 11 August 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
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p. 227-249
by  and
Life 2014, 4(2), 227-249; doi:10.3390/life4020227
Received: 30 January 2014; in revised form: 23 April 2014 / Accepted: 25 April 2014 / Published: 20 May 2014
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(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
p. 131-141
by , , ,  and
Life 2014, 4(2), 131-141; doi:10.3390/life4020131
Received: 27 February 2014; in revised form: 28 March 2014 / Accepted: 31 March 2014 / Published: 10 April 2014
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: In Vitro Selected Ribozymes
Author: Ulrich F. Müller
Affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, USA
Abstract: The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genomes and as the only genome-encoded catalyst. This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory, for a wide range of reactions that might have been used by RNA world organisms. The focus of this review is to: summarize which ribozymes have been generated in the lab; describe some of their selection procedures; briefly discuss their relevance to RNA world scenarios; and to describe what future developments are required to generate an RNA world organism in the lab.

Title: Acytota: Neglected Kingdom of Life
Edward N. Trifonov 1 and Eduard Kejnovsky 2
1 Genome Diversity Center, Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel
Department of Plant Developmental Genetics, Institute of Biophysics ASCR, Kralovopolska 135, 61265 Brno, Czech Republic
There is a huge variety of RNA- and DNA-containing entities which multiply within and propagate between cells of all kingdoms of life, having no cells of their own. Apart of cellular organisms these entities (viroids, plasmids, mobile elements, viruses and others) are the only ones which have their distinct genetic identities, but not included in any kingdom of life, since all the traditional kingdoms are cellular. We suggest to introduce the distinct category of the acellular organisms, Acytota, as an additional, undeservedly ignored kingdom of life. Acytota are indispensable for cellular life and its evolution. Six traditional kingdoms (Cytota) together with Acytota complete the classification of biological world (Biota), leaving nothing life-like beyond.

Title: The Origin and Evolution of Ribonucleotide Reduction—A Repeated History of Reciprocal Dependencies
Daniel Lundin 1, Gustav Berggren 1, David Nord 1, Derek Logan 2 and Britt-Marie Sjöberg 1
1 Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden
Department of Biochemistry and Structural Biology, Lund University, Box 124, SE-221 00 Lund, Sweden
: Ribonucleotide reduction is the only pathway for de novo synthesisof deoxyribonucleotides in extant organisms. Ribonucleotide reductase (RNR) catalyses the reaction, which is chemically demanding and involves a carbon-based radical. The mechanism has been deemed unlikely to be catalysed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesised at the transition from RNA to DNA encoded genomes. While it is entirely possible that a different pathway was used, later to be replaced with the extant mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA+protein world and suggest a model for a proto typical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to extant RNRs, the urRNR, which diversified to the extant three classes characterised mainly by how the radical is initially generated. Subsequent to the origin of the three classes, RNRs have undergone further specialisations, and we describe a phylogenetic subclassification of the enzyme family. RNR genes are frequent hosts of selfish genetic elements—introns and inteins—and we observe an interesting organism distribution of classes and subclasses indicating both short and long-range horizontal transfer of RNR genes.

Title: Characterization of RNA-like oligomers from lipid-assisted nonenzymatic synthesis: Implications for origin of informational molecules in the RNA world
Chaitanya Mungi 1 and Sudha Rajamani 1,*
Indian Institute of Science Education and Research, Pune, Maharashtra 411008 India
Formation of informational molecules is a crucial step in the origin of life. In modern biology, fundamental functions like information storage and catalysis are carried out by specialized polymers, whose polymerization is orchestrated by enzymes that use activated monomers. However, prebiotic polymerization had to be a nonenzymatic chemically driven process that used non-activated monomers. Chemical polymerization of monomers is the result of a condensation reaction; an uphill event which is particularly favored in scenarios that push reaction regimes far from equilibrium conditions. Dehydration-rehydration (DH-RH) cycles are one such regime which is thought to have been common on prebiotic Earth. These would have been prevalent in niches like inter-tidal and geothermal pools, which would have been driven by day-night cycles and seasonal variations. In the present study, we undertook detailed characterization of reaction conditions under which lipid-assisted nonenzymatic polymerization of nucleoside 5’-monophosphates is optimum. In addition, the resultant products were characterized using biochemical methods to delineate their chemical makeup and understand the plausible reaction mechanism that drove their formation. Importantly, our study demonstrates that the resultant RNA-like oligomers have abasic sites which result from low pH and high temperatures that drive these uphill reactions; conditions encountered in acidic geothermal pools. In other words, these RNA-like oligomers lack information carrying capability because of loosing most of their heterocyclic bases during the reaction process. Interestingly, sugar-phosphate backbones however readily form under these reaction conditions when ribose 5’-monophosphate is used as the starting monomer. Formation of such backbones would have permitted sampling of a large variety of bases on a preformed polymer backbone. Our results support what is increasingly considered to be a more prebiotically realistic scenario for the origin of the RNA world as it is thought that the native bases in extant biology (A, U/T, G and C) may actually have resulted from fine tuning of a chemical evolutionary process. And, very early on in this process, primordial informational polymers would have utilized simpler bases that might have conferred greater N-glycosyl bond stability; a feature crucial for information propagation in low pH and high temperature regimes of early Earth.

Title: How Amino Acids and Peptides Shaped the RNA world
Peter van der Gulik and Dave Speijer
Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
The “RNA world” hypothesis is seen as one of the main contenders for a viable theory on the origin of life. Relatively small RNAs have catalytic power, RNA is everywhere in present-day life, the ribosome is seen as a ribozyme, and rRNA and tRNA are crucial for modern protein synthesis. However, this view may be incomplete.The modern protein-RNA ribosome, though at its core an RNA structure, possibly started out with amino acids and tiny peptides playing an essential role. The ancient peptidyl transferase center might have emerged in close connection with ancient aminoacylated tRNAs. Small RNAs and amino acids, as well as tiny peptides, probably coevolved. Remember, it is the amino group of aminoacylated tRNA that attacks peptidyl-tRNA destroying the bond between peptide and tRNA. This activity of the amino acid part of aminoacyl-tRNA illustrates the centrality of amino acids in life. With the rise of the “RNA world” view of early life, the pendulum seems to have swung too much towards the ribozymatic part of early biochemistry. The necessary presence and activity of amino acids and peptides is in need of highlighting. In this article, we try to bring the role of the peptide component of earlylife back into focus. We argue that an RNA world independent of amino acids never existed.

Last update: 31 October 2014

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