The Evolution of RNA and DNA: A Shared History

Abstract

RNA and DNA are molecules that are essential to all life. Many researchers have theorized that RNA preceded DNA as a genetic blueprint, evidenced by its simpler structure and its multifunctional ability to act like a code, a protein, and an enzyme. Summarizing current research on the subject, this paper will examine the structure, function, and evolution of RNA and DNA, including theories on how RNA and DNA originally evolved and experimental evidence that supports or disputes these theories. A better understanding of how DNA was adopted over RNA by a majority of life-forms opens up new avenues for research in medicine and the life sciences.

Introduction

DNA is the blueprint of life. While it's the common bond of the human family tree, from the smallest cell to the largest creatures on Earth, almost every form of life relies on DNA to carry out the processes of growth, development, metabolism, and evolution. However, without the essential contributions of RNA, DNA would not be able to carry out these functions. Some scientists have proposed that before DNA was the primary informational molecule for life, RNA, or an even simpler, similar molecule, a pre-RNA, was responsible for many of the same activities, such as replication, protein synthesis, and other hallmarks of life. Early experiments in the field of abiogenesis, which seeks to shed light on how life arose from non-life, led scientists such as Miller and Urey to conclude in 1951 that naturally occurring chemicals could be subjected to conditions such as heat and electricity to form more complex organic molecules such as amino acids, the precursors to proteins (Lewis, 348). Early RNA molecules were probably naturally synthesized in a similar process. There are many different theories as to how RNA originally developed, and then gave way to the predominance of DNA as the universal genetic code. By examining scientific evidence concerning the structure, origin, and evolution of RNA and DNA, significant insights can be gained for many cutting edge fields such as xenobiology and forensic science, which have wide-reaching implications for society. Desert dwellers must be concerned with the evolution of DNA and RNA because the complex desert ecosystem relies on many unique adaptations that can be studied in depth by examining genetic material. For example, Valderrama-Cháirez, Cruz-Hernández, and Paredes-López (2002) found a good method of extracting RNA from prickly pear (Opuntia ssp.) fruit to study its metabolism and improve yields and quality in the future.

Methods

The authors reviewed here utilized different methodologies depending on the scope of their research. Focusing on summaries of current research and empirical data, the following studies generally took both a retrospective and prospective approach.

Forterre, Myllykallio, & Filée, (2013) analyzed DNA replication of Okazaki fragments in their laboratory across the three different domains of life. Jonsson (1996) examined the chemical stability of RNA and DNA bases using a multivariate quantitative physicochemical characterization. Lin and Patei (1997) examined the structure of DNA and RNA using nuclear magnetic resonance. Seoighe, Gehring, and Valcarcel (2010) used Affymetrix exon microarray data from the International HapMap project to examine the heritability of mRNA degradation. Theimer, Blois, and Feigon, (2005) looked at properties of the solution structure of the telomerase enzyme. Valderrama-Cháirez, Cruz-Hernández, and Paredes-López (2002) presented a novel method of extracting RNA from polysaccharide-rich fruits such as cactus fruit which used a procedure involving ethanol and liquid nitrogen to extract RNA and ran agarose gels to test for RNA.

In addition to these empirical studies, the overview of current and historic research found in Lewis (2004), Clancy (2014) and Talaro (2008) is fundamental in understanding the way that these specific facts and facets allow for a cohesive view of the interplay and evolution of RNA and DNA over time. This paper aims to overcome any specific methodological limitations by having a broad focus which includes both narrow empirical studies and general summaries.

Results

According to the results gathered, RNA and DNA have structural commonalities: they are both nucleic acids that contain a sugar backbone and organic bases. However, RNA and DNA have distinct structures and components which set them apart. RNA is composed of a D-ribose backbone; this sugar is a pentose monosaccharide with a hydroxyl group on its C2 Carbon atom (Clancy, 2014). In its open form, it contains an aldehyde group at one end, whereas in the ringed form found in RNA, a “phosphodiester linkage connects the 5’ phosphate group and the 3’-OH group of adjoining nucleotides” (Clancy, 2014).

DNA, on the other hand, is composed of a 2-deoxyribose backbone, this sugar lacks the hydroxyl group of ribose which is theorized to allow for greater flexibility, and hence a double helical structure and greater overall length. In eukaryotes, this flexibility also allows DNA to be tightly folded inside a chromosome. 2-deoxyribose is a modified form of ribose which has been reduced. RNA is generally single-stranded, however, it can “hybridize” and form double-stranded structures, including between RNA and DNA, this ability is important to its actions inside the cell (Clancy, 2014). Not only that, like proteins, but RNA can also form complex 3-dimensional structures consisting of secondary and tertiary forms of intricate loops (Clancy, 2014). This structural complexity demonstrates that RNA was capable of performing many of the roles that DNA now plays in current lifeforms. RNA contains the purine nitrogenous bases adenine and guanine and the pyrimidine nitrogenous bases cytosine and uracil. There were probably many intermediate steps in the evolution of RNA to DNA structurally, including one where RNA played a larger role in cellular functioning and DNA a smaller one.

The direction of replicase action is also evidence of a transition from RNA to DNA, as “purine and pyrimidine biosyntheses are built up on ribose 5 monophosphate as a common precursor” (Forterre, Myllykallio & Filee, 2013). The nitrogenous bases found in DNA are adenine, guanine, cytosine, and thymine. Thymine is a modified form of uracil, which, in turn, can be a degraded form of cytosine (Jonsson, 1996). Some rare microorganisms utilize uDNA or DNA which contains uracil as a base, and some scientists believe they are extant species showing an evolutionary link between RNA and DNA.

The aptamers that grab AMP show similarity between RNA and DNA, though they have different “tertiary structures and binding stoichiometries” (Lin and Patei, 1997). Nevertheless, AMP targets both of these aptamers through the same mechanism: “intercalating through purine bases and through identical G-A mismatch formation” (Lin & Patei, 1997). Like two keys cut slightly differently from the same guide, the aptamers found in RNA and DNA are related because of their shared evolutionary history.

Recent research has demonstrated that methods of DNA synthesis probably evolved separately multiple times (Forterre, et al., 2013). Another possible avenue for the evolution of DNA was in ancient viruses, who may have evolved DNA for multiple reasons, such as the ability to resist RNAase enzymes which confers an evolutionary advantage in terms of immunity (Forterre, et al., 2013). Organisms in the domain archaea and those in bacteria have different methods of DNA synthesis. Some of the proteins used by archaea are more closely related to those found in eukaryotes than the synthesizing proteins used by prokaryotic bacteria. This is even though archaea and bacteria have similar overall morphology and general metabolic and reproductive style. This suggests that archaea and all eukaryotes share a common ancestor which gave them their DNA reproducing proteins; this ancestor branched off from the one which passed on its code to bacteria or it is possible that DNA evolved separately in different places and times in ancient lifeforms (Forterre, et al., 2013).

The main biochemical development which allowed RNA to evolve into DNA was the formation of reverse transcriptase; this allowed RNA to be copied into DNA (Lewis, 2004). Before the chain from DNA to RNA to protein existed, RNA likely coded for rudimentary proteins by itself. After attaining sufficient length, and a working sequence coding for amino-acids, reverse transcriptase evolved. This meant that DNA could be used to hold genetic information safely away from metabolic reactions, while RNA could still play the messaging, transport, and enzymatic roles it does today through tRNA, mRNA, and rRNA (Lewis, 2004).

The ability of RNA to catalyze its own synthesis, while DNA requires a small piece of RNA to begin replication, strongly suggests that RNA predates DNA as a biological blueprint molecule. Forterre, et al. (2013) argue that “the synthesis of DNA building blocks from RNA precursors is a major argument in favor of” the evolution from RNA to DNA and that “DNA synthesis itself is…a relic of the RNA world metabolism.” There is variability in the way that RNA translates genes to be expressed within an individual’s cells, and among different individuals in a population (Seoighe, et al., 2010).

This means that RNA’s role as an intermediary is vital because it allows for genes to be expressed in specific ways, and for the rates of different forms of expression to be heritable as well. Cao, et al. (2011) investigated the relationship between telomere dysfunction and progerin in causing cellular aging and the disease progeria. RNA performs an enzymatic function as part of Telomerase, which is an enzyme essential to human cell function, as it helps to keep the biological clock with the telomeres which are attached to chromosomes. Telomeres cannot be added to a new chromosome with DNA polymerase, and so “progressive shortening” will occur unless the combination of reverse transcriptase and RNA found in telomerase act to control telomere length (Cao, et al., 2011). Cell immortality, found in cancer, also corresponds to “persistent telomerase expression” (Cao, et al., 2011).

RNA likely played a greater role in enzymatic catalysis before the advent of DNA. Ribozymes are evidence of this theory (Talaro, 2008). The longer codes allowed by DNA led to the production of more intricate and specified proteins for carrying out cell metabolism. RNA can be found in a self-replicating form independently as viroids, self-replicating pathogens that inflict disease, including on plants (Lewis, 2004). Viroids demonstrate “naked,” “double-stranded RNA that host cell enzymes” are unable to degrade because of its coiled nature (Lewis, 2004). Viroids can be transmitted mechanically through contact or by hereditary means (Lewis, 2004). Scientists have developed biotechnological remedies for plant viroids including transgenic potatoes with a yeast gene enabling the ability to attack viroids (Lewis, 2004).

Self-catalyzing enzymes composed of RNA called ribozymes which are found in cells have important medical implications, including the use of genetically engineered ribozymes in treatments for “cancer and AIDS” (Talaro, 2008).

Discussion and Conclusions

It is fascinating to consider the complex elegance of the RNA-DNA dance which takes place in every living cell. In some of the earliest life forms, self-replicating RNA allowed for the evolution of life’s essential chemicals on a molecular scale. Selection pressures on this RNA included rate of reproduction, error correction, and overall stability. Like on Earth today, there were probably RNA life forms that resembled viruses, and their infectious presence may have driven their victims toward the evolution of DNA. Before modern molecular biological methods of examining molecules of DNA, RNA, or proteins, scientists believed that DNA evolved only once in a last common ancestor and then took over as the predominant genetic code; however, some have suggested that it may have evolved at different times and in different contexts. An early virus may have even been the first creature to form DNA. The formation of reverse transcriptase was the keystone in building the first DNA molecules from RNA. Before that, RNA likely acted as a self-catalyzing enzyme and code in the early history of life.

Whichever evolutionary pathway it took, DNA outcompeted RNA among early life-forms because it allowed for organisms that could adapt to the environment in increasingly complex ways and synthesize larger chemicals such as complicated, specifically acting proteins. In today’s ecological state, the three domains of life all use different methods of DNA synthesis, indicating a complex evolutionary history pointing to an RNA to DNA transition that may have occurred multiple times over the history of life. Scientists are finally beginning to fully understand the meanings and implications of DNA’s role in life through genetic sequencing and analyzing in detail its molecular structure, chemical interactions, and heritability. How DNA carries out cellular activities is based on multiple types of RNA working together, including the RNA inside the structure of the ribosome itself which synthesizes proteins, the products of the messages encoded in DNA. Scientists are just beginning to realize how large a role RNA plays in evolution, as a mediator of gene expression which is also subject to RNA-specific selective pressures (Seoighe, Gehring, & Valcarcel, 2010). The epigenetic relationship between RNA and DNA demonstrates that they are evolving together, in ways both parallel and intersecting. If the hypothesis that RNA evolved into DNA through many modifications is true, then the ways that extant life forms use DNA and RNA in interlocking processes strongly suggests that RNA continues to evolve within the cells of contemporary species.

New drugs are being developed based on custom-made snippets of RNA which carry out various, highly-targeted functions within the body to treat disease. The relationship between RNA, telomerase, the chromosome, and progerin production has important medical implications including cancer treatment, anti-aging therapies, and possible cures for rare diseases like progeria. Although some geneticists are more concerned with current forms of life than the origin and evolution of their molecular blueprints, a greater understanding of the history, mechanisms, and scales of time which allowed for RNA to evolve into DNA, will shed light on the evolutionary processes which occur today. Extant examples such as Viroids, whose DNA-like RNA structure, ability to propagate themselves, and evolutionary longevity show that they have some of the properties likely found in an RNA world proving that the RNA to DNA transition could happen gradually in living creatures of the past. The evolutionary forces acting in ancient times were similar to those in place today.

Desert dwellers should be concerned about evolution as it relates to crop safety and sustainability, especially in desert crops such as avocados and prickly pear fruit. Research into viroids and the extraction of plant DNA and RNA is aiding farmers (Lewis, 2004) (Valderrama-Cháirez, et al., 2002). Further research into likely modes of RNA to DNA evolution should focus on examining the genomes of ancient viruses, rare microorganisms, and extremophiles for molecular fossils which might indicate more specifically the nature of this important evolutionary milestone. Understanding how an organism’s molecules evolve helps to understand the larger interplay of ecological systems and the interlocking mechanisms of evolution. Biotechnology opens the doors to custom-made DNA, RNA, and XNA sequences that serve human needs, whether in research, industry, or medicine. This is the forefront of many converging fields and scientists must engage in ethical discourse with an eye toward evolutionary history to move forward on a steady course into the bewildering future.

References

Clancy, S. (2014) Chemical structure of RNA. Nature Education 7(1):60

Lewis, R. (2004). Life (5th ed.). Boston, Mass.: WCB/McGraw-Hill. pp. 350-356, 370-381

Forterre, P., Myllykallio, H., & Filée, J. (2013). Origin and Evolution of DNA and DNA Replication Machineries. Madame Curie Bioscience Database. Retrieved April 1, 2014, from http://www.ncbi.nlm.nih.gov/books/NBK6360/

Jonsson, J. (1996). The Evolutionary Transition from Uracil to Thymine Balances the Genetic Code Journal of Chemometrics, 10, 163-170

Lin, C. H., & Patei, D. J. (1997). Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP. Chemistry & Biology, 4(11), 817-832.

Seoighe, C., Gehring, C., & Valcarcel, J. (2010). Heritability in the Efficiency of Nonsense-Mediated mRNA Decay in Humans. PLoS ONE, 5(7), e11657.

Talaro, K. P. (2008). Foundations in microbiology (6th ed.). New York, NY: McGraw-Hill. pp. 22-23, pp. 222

Theimer, C. A., Blois, C. A., & Feigon, J. (2005). Structure of the Human Telomerase RNA Pseudoknot Reveals Conserved Tertiary Interactions Essential for Function. Molecular Cell, 17(5), 671-682.

Valderrama-Cháirez, M. L., Cruz-Hernández, A., & Paredes-López, O. (2002). Isolation of functional RNA from cactus fruit. Plant Molecular Biology Reporter, 20(3), 279-286.