**1. Introduction**

Protocellular organisms may have come into existence 2.5 to 3.5 billion years ago [1, 2]. Woese [3] proposed that the genomes of the early protocellular forms of life were individual strands of RNA rather than DNA, and that these RNA strands were present as separate genome segments, rather than being linked together end-to-end as is generally the case for genes in DNA. The idea that, during an early period in the evolution of life, genetic information was stored and transmitted solely by RNA molecules has come to be known as the "RNA world hypothesis." This hypothesis is currently being tested by many investigators. Of particular significance, Horning and Joyce [4] have demonstrated that the replication of genetic information and its conversion into functional molecules can be accomplished with RNA in the complete absence of protein. RNA molecules with catalytic activity are called ribozymes. An RNA ribozyme developed by Horning and Joyce can act as an RNA polymerase to replicate RNA [4].

Persistence and replication of even the simplest forms of RNA life must have depended on preserving the information content of the RNA genome from damage (a form of informational noise). Damage to the RNA genome likely occurred in a variety of ways including spontaneous hydrolysis, exposure to UV light and exposure to reactive chemicals. Natural selection would have acted to promote the evolution of RNA sequences that allowed solutions to this problem of informational noise. While free living organisms with ssRNA genomes are unknown in today's world, viruses with ssRNA genomes are currently common. The present day ssRNA viruses also need to cope with informational noise in the form of damage to their RNA genome. Therefore, such ssRNA viruses can serve as models for understanding the adaptive solutions that early ssRNA protocells may have developed for coping with genome damage. Numerous ssRNA viruses have been shown to be capable of exchanging sequence information between individual genomes within an infected cell [5]. This information exchange, or genetic recombination, can occur by reassortment of genome segments or during genome replication by a process of strand-switching to form a progeny genome with information from two parental genomes. The process of strand-switching is often referred to as "copy-choice" recombination. The term "copy-choice" embodies the idea of template-switching during genome replication, although the term was introduced before the DNA/RNA nature of genetic information was understood. Lederberg [6] and Bernstein [7] were among the first to explicitly propose copy-choice mechanisms of recombination. The two recombination processes, segment reassortment and copy-choice, allow the formation of an undamaged progeny genome even when one or both parental genomes contain damage. In the sense that both segment reassortment and copy-choice restore genetic sequence information that is damaged in the parental genomes, these are informational repair processes. Although information is restored in progeny, the parental genomes may retain their physical damage. Thus when "repair" is discussed at the level of ssRNA organisms it is the genetic information content of damaged parental genomes that is restored or "repaired" during formation of the progeny genome.

The role of RNA segment reassortment in genome repair is discussed by Bernstein et al. [8] and the role of copy choice recombination in an RNA genome repair is discussed by Hu and Temin [9].

As the early protocells with RNA genomes evolved they likely went through a series of adaptive transitions that eventually led to the double-stranded DNA (dsDNA) genome. The archaea are a group of prokaryotes with a dsDNA genome that likely evolved prior to the emergence of eukaryotes. These organisms are capable of a process, genetic transformation, during which cells exchange DNA to repair DNA double-strand breaks via homologous recombination [10]. In eukaryotes, during meiosis and mitosis, most recombination events occur by a repair process termed "synthesis-dependent strand annealing" (SDSA) [11] that is basically a form of copy-choice recombination (see Section 6.1.). In addition, single-strand damages that block the movement of the DNA polymerase during replication can be repaired by a mechanism that includes copy-choice recombination [12, 13]. Thus strandswitching copy-choice mechanisms that likely emerged in early ssRNA protocells appear to have evolved into fundamental processes for maintaining the information content of dsDNA genomes.

While the capability for recombinational repair is retained as a major mechanism for dealing with DNA damages, organisms with a dsDNA genome, including humans, have also evolved other repair processes that take advantage of the duplex nature of the DNA genome [14]. For such organisms, damages in one strand can be repaired by removal of the damaged section and its replacement by copying information from the other strand, as occurs in the well-studied processes of mismatch repair, nucleotide

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ribozyme function [8].

evolution of cellular life [8].

*Origin of DNA Repair in the RNA World DOI: http://dx.doi.org/10.5772/intechopen.93822*

**2. Genome repair in the RNA world**

excision repair and base excision repair [14]. Other processes for dealing with DNA damages in organisms with DNA genomes include direct reversal of UV photolesions and alkylated bases, repair of DNA crosslinks by Fanconi anemia proteins, and a

The aim of this review is to outline how genome repair processes emerged in the earliest evolved protocells that likely had RNA genomes, and how these processes

Since the actual sequence of evolutionary adaptive events in the RNA world that gave rise to genome repair occurred in organisms that are probably long extinct, and it is unlikely that events at the nucleic acid level are preserved in the fossil record, the sequence of evolutionary events proposed here is necessarily speculative. However, the proposed evolutionary sequence is based on the established activities of extant RNA viruses. These activities are reviewed in sections 2.1, 2.2, 3 and 4. Thus it is assumed, as discussed by Bernstein et al. (pgs. 342-345) [8], that the adaptations that extant RNA viruses use to repair genome damage can illumi-

mechanism for tolerating damages termed translesion synthesis [15].

further evolved in the transition from the RNA world to the DNA world.

nate how early life in the RNA world also coped with genome damage.

In early protocellular organisms the genome is thought to have consisted of ssRNAs (genes) that formed folded structures with catalyic activity (ribozymes) [16]. If two or more such ssRNAs were present in a protocell they presumably functioned interdependently to promote the viability and reproduction of the protocell. A key ribozyme in early protocellular organisms would likely have been a polymerase that could catalyze RNA replication [4]. A persistent problem for early protocellular organisms would probably have been damage to their ssRNA genomes. The damaging stresses on protocellular organisms likely would have included hydrolytic reactions, exposure to UV light and interaction with reactive chemicals in the environment. For example, Sagan [17] analyzed the flux of solar UV light that penetrated the earth's primitive reducing atmosphere. His analysis indicated that unprotected microorganisms of the type existing today would receive a mean lethal dose at 2600 angstroms within 0.3 seconds and that this vulnerability could have posed a major problem during the early evolution of life. A protocell that has only one copy of each ssRNA (a haploid protocell) would be very vulnerable to damage, since damage to even one base in a ssRNA sequence might be lethal to the protocell by either blocking replication of the ssRNA or interfering with an essential ssRNA

One possible adaptation for dealing with genome damage would be to maintain two or more copies of each ssRNA gene in each protocell, yielding a diploid or polyploid state. Genome redundancy would allow replacement of a damaged gene by an additional replication of an undamaged homologous gene. However, for a simple protocellular organism, the proportion of available resource budgeted to the maintenance of two or more genomes would have been a large portion of its total resource budget. When resources are limited, the protocell's reproductive rate would likely be inversely related to ploidy number. The fitness of the protocell would be diminished by the costs of genome redundancy. Coping with damage to the ssRNA genome while minimizing the costs of genome redundancy would likely have been a fundamental problem in the early

When the costs of maintaining genome redundancy verses the costs of genome damage were balanced against each other in a cost–benefit analysis, it was found that under a wide range of conditions the selected strategy would be for each

*DNA - Damages and Repair Mechanisms*

formation of the progeny genome.

content of dsDNA genomes.

repair is discussed by Hu and Temin [9].

Persistence and replication of even the simplest forms of RNA life must have depended on preserving the information content of the RNA genome from damage (a form of informational noise). Damage to the RNA genome likely occurred in a variety of ways including spontaneous hydrolysis, exposure to UV light and exposure to reactive chemicals. Natural selection would have acted to promote the evolution of RNA sequences that allowed solutions to this problem of informational noise. While free living organisms with ssRNA genomes are unknown in today's world, viruses with ssRNA genomes are currently common. The present day ssRNA viruses also need to cope with informational noise in the form of damage to their RNA genome. Therefore, such ssRNA viruses can serve as models for understanding the adaptive solutions that early ssRNA protocells may have developed for coping with genome damage. Numerous ssRNA viruses have been shown to be capable of exchanging sequence information between individual genomes within an infected cell [5]. This information exchange, or genetic recombination, can occur by reassortment of genome segments or during genome replication by a process of strand-switching to form a progeny genome with information from two parental genomes. The process of strand-switching is often referred to as "copy-choice" recombination. The term "copy-choice" embodies the idea of template-switching during genome replication, although the term was introduced before the DNA/RNA nature of genetic information was understood. Lederberg [6] and Bernstein [7] were among the first to explicitly propose copy-choice mechanisms of recombination. The two recombination processes, segment reassortment and copy-choice, allow the formation of an undamaged progeny genome even when one or both parental genomes contain damage. In the sense that both segment reassortment and copy-choice restore genetic sequence information that is damaged in the parental genomes, these are informational repair processes. Although information is restored in progeny, the parental genomes may retain their physical damage. Thus when "repair" is discussed at the level of ssRNA organisms it is the genetic information content of damaged parental genomes that is restored or "repaired" during

The role of RNA segment reassortment in genome repair is discussed by Bernstein et al. [8] and the role of copy choice recombination in an RNA genome

As the early protocells with RNA genomes evolved they likely went through a series of adaptive transitions that eventually led to the double-stranded DNA (dsDNA) genome. The archaea are a group of prokaryotes with a dsDNA genome that likely evolved prior to the emergence of eukaryotes. These organisms are capable of a process, genetic transformation, during which cells exchange DNA to repair DNA double-strand breaks via homologous recombination [10]. In eukaryotes, during meiosis and mitosis, most recombination events occur by a repair process termed "synthesis-dependent strand annealing" (SDSA) [11] that is basically a form of copy-choice recombination (see Section 6.1.). In addition, single-strand damages that block the movement of the DNA polymerase during replication can be repaired by a mechanism that includes copy-choice recombination [12, 13]. Thus strandswitching copy-choice mechanisms that likely emerged in early ssRNA protocells appear to have evolved into fundamental processes for maintaining the information

While the capability for recombinational repair is retained as a major mechanism for dealing with DNA damages, organisms with a dsDNA genome, including humans, have also evolved other repair processes that take advantage of the duplex nature of the DNA genome [14]. For such organisms, damages in one strand can be repaired by removal of the damaged section and its replacement by copying information from the other strand, as occurs in the well-studied processes of mismatch repair, nucleotide

**22**

excision repair and base excision repair [14]. Other processes for dealing with DNA damages in organisms with DNA genomes include direct reversal of UV photolesions and alkylated bases, repair of DNA crosslinks by Fanconi anemia proteins, and a mechanism for tolerating damages termed translesion synthesis [15].

The aim of this review is to outline how genome repair processes emerged in the earliest evolved protocells that likely had RNA genomes, and how these processes further evolved in the transition from the RNA world to the DNA world.
