Inevitability of Genetic Parasites

“The inevitability of the emergence of parasites has figured prominently in theoretical studies on the origin of life (Szathmary and Demeter 1987; Szathmary 1992; Maynard Smith and Szathmary 1995; Koonin and Martin 2005; Takeuchi and Hogeweg 2012).”

“This observation suggests a fresh outlook on the “selfish gene” concept (Doolittle and Sapienza 1980; Orgel and Crick 1980; Dawkins 2006).”

“This trend is indeed strikingly apparent in microbes whose life style leads to curtailment of HGT, such as obligate endosymbiotic bacteria (Moran 1996; Mamirova et al. 2007; Moran et al. 2008).”

“…large fractions of the genomes of diverse eukaryotes, (e.g., up to 90% of many plant genomes) and are considered to be important drivers of genome evolution (Kazazian 2004; Hua-Van et al. 2005; Jurka et al. 2007; Goodier and Kazazian 2008; Huda and Jordan 2009; Lopez-Flores and Garrido-Ramos 2012).”

“This trend is indeed strikingly apparent in microbes whose life style leads to curtailment of HGT, such as obligate endosymbiotic bacteria (Moran 1996; Mamirova et al. 2007; Moran et al. 2008).”

“Although these costs are presumably small for many if not most non-viral selfish elements (Lynch 2007), the relatively low copy numbers of such elements in prokaryotic genomes imply that host populations are able to keep them under control (Lynch 2006b; Wolf and Koonin 2013).”

“Although genomic parasites are not quite as prominent in prokaryotes, there are few bacterial or archaeal genomes that are free of selfish, parasitic elements including transposons and prophages (Casjens 2003; Busby et al. 2013).”

“Parasite–host interaction and co-evolution undoubtedly are major aspects of all evolution of life that to a large extent drive evolutionary transitions (May and Anderson 1990; Messinger and Ostling 2009; Koskella and Brockhurst 2014; Leggett et al. 2014; Gorter et al. 2015; Koonin 2016).”

“The first strategy is consistent with the general observation that, in prokaryotes, deletions are more frequent than insertions and the rate of gene loss exceeds the rates of gene acquisition and gene duplication (Andersson and Andersson 1999, 2001; Mira et al. 2001; Kuo and Ochman 2009).”

“Horizontal gene transfer (HGT) is a dominant process in the evolution of bacteria and archaea that is the source of most innovations and adaptations to new environments (Lerat et al. 2005; Dagan et al. 2008; Koonin and Wolf 2008; Treangen and Rocha 2011; Puigbo et al. 2014).”

“Therefore, transformation can be not only a source of genetic innovation (Croucher et al. 2011; Johnston et al. 2014) but also a means of transmission of genetic parasites.”

“Specifically, population genetics models show that, in a population of size N, Muller’s ratchet drives the accumulation of mutations with the cost s’ such that Ns 0 > 1 > Ns 0 e U=s 0 , where U is the rate at which such mutations occur (Gordo and Campos 2008).”

“Eventually, the “reduced costs” strategy is bounded by the energy cost associated to the replication of the additional genetic material (Lynch and Marinov 2015) which likely sets a limit to the size of non-beneficial elements that do not encode autonomous transfer mechanisms.”

“…strains from filarial nematodes (Brugia malayi and Onchocerca ochengi) are transmitted in a strict vertical manner that (virtually) excludes HGT (Bandi et al. 1998), and their genomes are characterized by the lack of prophages and functional insertion sequences (Foster et al. 2005; Cordaux…”

“In line with its major evolutionary impact, avoidance of Muller’s ratchet is thought to be one of the key driving forces in the evolution of sex (Kondrashov1988, 1993; Gordo and Campos 2008; Hartfield and Keightley 2012).”

“…in several prokaryotes are typically of the order of one (Posada et al. 2000; Feil et al. 2001; Sarkar and Guttman 2004; Lynch 2006a; Vos and Didelot 2009), with a median of approximately 1.5 (Q1–Q3 equal to 0.5 and 7, respectively) when pooling data from Lynch (2006a) and Vos and Didelot (2009).”

“A major aspect of this co-evolution is the perennial arms race whereby cellular hosts evolve multiple mechanisms of defense to which the parasites respond by evolving counter-defense systems (Forterre and Prangishvili 2009; Stern and Sorek 2011; Forterre and Prangishvili 2013).”

“Horizontal gene transfer (HGT) is a dominant process in the evolution of bacteria and archaea that is the source of most innovations and adaptations to new environments (Lerat et al. 2005; Dagan et al. 2008; Koonin and Wolf 2008; Treangen and Rocha 2011; Puigbo et al. 2014).”

“…between different life styles, e.g., between low cost prophages and high cost lytic viruses, as in the thoroughly studied case of temperate bacteriophages (Canchaya et al. 2003; Los and Wegrzyn 2012; Casjens and Hendrix 2015), or between a bacteriophage and a plasmid (Briani et al. 2001).”

“…the ratio between recombination and mutation rates in several prokaryotes are typically of the order of one (Posada et al. 2000; Feil et al. 2001; Sarkar and Guttman 2004; Lynch 2006a; Vos and Didelot 2009), with a median of approximately 1.5 (Q1–Q3 equal to 0.5 and 7, respectively) when pooling…”

“Genetic parasites are non-cellular replicators that possess their own genomes but to various degrees depend on the host cells for information processing systems, in particular translation (Raoult and Forterre 2008).”

“A major role of viruses in the host biology has also been demonstrated in prokaryotes as illustrated by the transfer of photosystem genes by cyanophages (Sullivan et al. 2006; Lindell et al. 2007), the utilization of defective prophages as vehicles for horizontal gene transfer known as Gene Transfer Agents (Lang et al…”

“M systems that target unmodified virus DNA but not DNA modified similarly to the host genome (Pleska et al. 2016) and CRISPR-Cas systems at least some of which appear to specifically target actively replicating DNA (Amitai and Sorek 2016).”

“The inevitability of the emergence of parasites has figured prominently in theoretical studies on the origin of life (Szathmary and Demeter 1987; Szathmary 1992; Maynard Smith and Szathmary 1995; Koonin and Martin 2005; Takeuchi and Hogeweg 2012).”

“The utility of the second choice, lowering the mutation rate, is limited by the power of genetic drift (Lynch 2011; Sung et al. 2012).”

“Horizontal gene transfer (HGT) is a dominant process in the evolution of bacteria and archaea that is the source of most innovations and adaptations to new environments (Lerat et al. 2005; Dagan et al. 2008; Koonin and Wolf 2008; Treangen and Rocha 2011; Puigbo et al. 2014).”

“…between different life styles, e.g., between low cost prophages and high cost lytic viruses, as in the thoroughly studied case of temperate bacteriophages (Canchaya et al. 2003; Los and Wegrzyn 2012; Casjens and Hendrix 2015), or between a bacteriophage and a plasmid (Briani et al. 2001).”

“…that are most typical of parasitic and symbiotic bacteria but appear to also occur in some free-living microbes (Lynch 2006b; Wolf et al. 2012; Wolf and Koonin 2013) could be either signs of genome degeneration along the path to extinction driven by Muller’s ratchet or a manifestation of…”

“All or nearly all cellular life forms appear to harbor diverse genetic parasites including transposable elements, plasmids, viruses, and others (Koonin and Dolja 2013).”

“…large fractions of the genomes of diverse eukaryotes, (e.g., up to 90% of many plant genomes) and are considered to be important drivers of genome evolution (Kazazian 2004; Hua-Van et al. 2005; Jurka et al. 2007; Goodier and Kazazian 2008; Huda and Jordan 2009; Lopez-Flores and Garrido-Ramos 2012).”

“The first strategy is consistent with the general observation that, in prokaryotes, deletions are more frequent than insertions and the rate of gene loss exceeds the rates of gene acquisition and gene duplication (Andersson and Andersson 1999, 2001; Mira et al. 2001; Kuo and Ochman 2009).”

“Estimation of Duplication, Loss and Transfer Rates from Genomic Data Genomic data were obtained from an updated version of the ATCG database that clusters genomes from bacteria and archaea into closely related groups (Novichkov et al. 2009; Puigbo et al. 2014).”

“Arthropodassociated strains of Wolbachia (e.g., those from Culex aculeatus and Drosophila melanogaster) are known to coinfect hosts and undergo HGT (Bordenstein and Wernegreen 2004; Baldo et al. 2006).”

“The first strategy is consistent with the general observation that, in prokaryotes, deletions are more frequent than insertions and the rate of gene loss exceeds the rates of gene acquisition and gene duplication (Andersson and Andersson 1999, 2001; Mira et al. 2001; Kuo and Ochman 2009).”

“Accordingly, it has been proposed that such a strong deletion bias could even be an adaptive trait that is selected for the beneficial effect of parasite elimination (Lawrence et al. 2001).”

“Arthropodassociated strains of Wolbachia (e.g., those from Culex aculeatus and Drosophila melanogaster) are known to coinfect hosts and undergo HGT (Bordenstein and Wernegreen 2004; Baldo et al. 2006).”

“Parasites are lost at two levels: at the genome level, the intrinsic loss bias observed in prokaryotic genomes leads to attrition of non-beneficial genes (Kuo and Ochman 2009, 2010); at the population level, purifying selection eliminates the hosts with the larger parasitic load (Lynch 2006b).”

“The utility of the second choice, lowering the mutation rate, is limited by the power of genetic drift (Lynch 2011; Sung et al. 2012).”

“To derive a condition for such a minimum HGT rate, we built upon the results of previous theoretical analyses that dealt with the mutation accumulation dynamics in finite populations (Rouzine et al. 2008; Neher and Shraiman 2012; Takeuchi et al. 2014).”

“A major aspect of this co-evolution is the perennial arms race whereby cellular hosts evolve multiple mechanisms of defense to which the parasites respond by evolving counter-defense systems (Forterre and Prangishvili 2009; Stern and Sorek 2011; Forterre and Prangishvili 2013).”

“…populations are subject to irreversible deterioration through accumulation of deleterious mutations, a process known as Muller’s ratchet, that eventually leads to the collapse of a population via mutational meltdown (Muller 1964; Felsenstein 1974; Pamilo et al. 1987; Charlesworth et al. 1993).”

“…genome streamlining that are most typical of parasitic and symbiotic bacteria but appear to also occur in some free-living microbes (Lynch 2006b; Wolf et al. 2012; Wolf and Koonin 2013) could be either signs of genome degeneration along the path to extinction driven by Muller’s ratchet or a…”

“The first strategy is consistent with the general observation that, in prokaryotes, deletions are more frequent than insertions and the rate of gene loss exceeds the rates of gene acquisition and gene duplication (Andersson and Andersson 1999, 2001; Mira et al. 2001; Kuo and Ochman 2009).”

“Thus, the primordial parasite-host arms race could have been a key driver of the evolution of biological complexity (Koonin 2016).”

“…8, 2016 The relationships between genomic parasites and their hosts are highly differentiated such that the parasites span a wide range of “selfishness,” i.e., the cost incurred on the host by the parasite reproduction (Jalasvuori 2012; Jalasvuori and Koonin 2015; Koonin and Starokadomskyy 2016).”

“The conditions required for the short- and long-term persistence of genetic parasites have been a recurrent topic in theoretical population biology after the discovery of selfish elements (Charlesworth and Charlesworth 1983; Langley et al. 1983; Kaplan et al. 1985; Moody 1988).”

“In asexual organisms, eDNA intake followed by recombination is the only way to counteract the mutation burden imposed by Muller’s ratchet (Takeuchi et al. 2014).”

“…generally, parasites can be eliminated from a population or at least kept in check if the rate at which the parasite is transferred to new hosts is insufficient to compensate for the loss of the parasite (Takeuchi and Hogeweg 2007; Takeuchi et al. 2011; Takeuchi and Hogeweg 2012).”

“Even if, in some cases, Muller’s ratchet can be partly offset by compensatory mutations (e.g., in the case of rapidly mutating RNA viruses), it still causes a dramatic drop in the fitness of susceptible populations (Lazaro et al. 2003).”

“Temperate viruses employ bet-hedging by taking advantage of the first strategy, while keeping the ability to autonomously transmit under conditions where the survival of the host is compromised (Maslov and Sneppen 2015).”

“Parasite–host interaction and co-evolution undoubtedly are major aspects of all evolution of life that to a large extent drive evolutionary transitions (May and Anderson 1990; Messinger and Ostling 2009; Koskella and Brockhurst 2014; Leggett et al. 2014; Gorter et al. 2015; Koonin 2016).”

“…between different life styles, e.g., between low cost prophages and high cost lytic viruses, as in the thoroughly studied case of temperate bacteriophages (Canchaya et al. 2003; Los and Wegrzyn 2012; Casjens and Hendrix 2015), or between a bacteriophage and a plasmid (Briani et al. 2001).”

“Although genomic parasites are not quite as prominent in prokaryotes, there are few bacterial or archaeal genomes that are free of selfish, parasitic elements including transposons and prophages (Casjens 2003; Busby et al. 2013).”

“…generally, parasites can be eliminated from a population or at least kept in check if the rate at which the parasite is transferred to new hosts is insufficient to compensate for the loss of the parasite (Takeuchi and Hogeweg 2007; Takeuchi et al. 2011; Takeuchi and Hogeweg 2012).”

“To derive a condition for such a minimum HGT rate, we built upon the results of previous theoretical analyses that dealt with the mutation accumulation dynamics in finite populations (Rouzine et al. 2008; Neher and Shraiman 2012; Takeuchi et al. 2014).”

“Parasite–host interaction and co-evolution undoubtedly are major aspects of all evolution of life that to a large extent drive evolutionary transitions (May and Anderson 1990; Messinger and Ostling 2009; Koskella and Brockhurst 2014; Leggett et al. 2014; Gorter et al. 2015; Koonin 2016).”

“The clusters of closely related prokaryotic genomes (Alignable Tight Genome Clusters, ATGC) (Novichkov et al. 2009; Puigbo et al. 2014) were employed as the data set for this analysis.”

“…are limited in scope, estimates for the ratio between recombination and mutation rates in several prokaryotes are typically of the order of one (Posada et al. 2000; Feil et al. 2001; Sarkar and Guttman 2004; Lynch 2006a; Vos and Didelot 2009), with a median of approximately 1.5 (Q1–Q3 equal to…”

“A major and striking theoretical result is that a spatially homogeneous population of replicators is prone to takeover by cheaters (parasites) and hence is generally doomed to collapse (Takeuchi and Hogeweg 2007).”

“Parasitic genetic elements can be beneficial to the host by providing resistance to superinfection but also in other, still incompletely characterized ways (Bao and Roossinck 2013; Shirogane et al. 2013).”

“The inevitability of the emergence of parasites has figured prominently in theoretical studies on the origin of life (Szathmary and Demeter 1987; Szathmary 1992; Maynard Smith and Szathmary 1995; Koonin and Martin 2005; Takeuchi and Hogeweg 2012).”

“This trend is indeed strikingly apparent in microbes whose life style leads to curtailment of HGT, such as obligate endosymbiotic bacteria (Moran 1996; Mamirova et al. 2007; Moran et al. 2008).”

“We revisited a general model that takes into account the effects of HGT, duplication, losses and selection to describe the fate of a selfish element in a host population (Moody 1988; Basten and Moody 1991; Bichsel et al. 2013; Iranzo et al. 2014).”

“We revisited a general model that takes into account the effects of HGT, duplication, losses and selection to describe the fate of a selfish element in a host population (Moody 1988; Basten and Moody 1991; Bichsel et al. 2013; Iranzo et al. 2014).”

“…genes by cyanophages (Sullivan et al. 2006; Lindell et al. 2007), the utilization of defective prophages as vehicles for horizontal gene transfer known as Gene Transfer Agents (Lang et al. 2012), and more generally by the recruitment of viral genes for diverse host functions (Cortez et al. 2009).”

“The other side of the coin is exemplified by Mycoplasma-related endobacteria: an association between parasite maintenance and avoidance of genome degeneration has been invoked to explain their evolutionary longevity as endosymbionts of mycorrhizal fungi (Naito and Pawlowska 2016).”

“We revisited a general model that takes into account the effects of HGT, duplication, losses and selection to describe the fate of a selfish element in a host population (Moody 1988; Basten and Moody 1991; Bichsel et al. 2013; Iranzo et al. 2014).”

“Parasitic genetic elements can be beneficial to the host by providing resistance to superinfection but also in other, still incompletely characterized ways (Bao and Roossinck 2013; Shirogane et al. 2013).”

“Both theory and observation indicate that persistence of MGEs of different kinds is virtually inevitable throughout the evolution of life (68, 78, 160).”

“…‘infection’ will persist at population level even after the elimination of the selection pressure and the consequent reduction of the fitness of the bacterium, which still carries a plasmid that now may be considered ‘useless’, or providing advantages at present not clearly understood [9, 47].”

“58 59–61 Considering these limitations of HGT along with (largely) non-overlapping vi-romes, 22 it could be expected that the co-occurrence of defense systems is poorly conserved among bacteria.”

“…suggest that emergence of selfish genetic elements is an intrinsic feature of replicator systems and that such elements were associated with cells from the earliest stages of the evolution of life and accompanied life forms throughout their subsequent diversification over ≈ 3.5 billion years [6-9].”

“Given that HGT, even if limited by both physical and selective barriers, remained a key factor of microbial evolution [36–40], and apparently, a condition for long term survival of microbial populations [41,42], it stands to reason that it played a key role not only in the primordial universalization of the code but a…”

“Theoretical argument 23 and empirical evidence strongly suggest that emergence of parasites is inevitable in replicator 24 systems [1-3].”

“The curtailment of HGT, in particular, could be a key factor that makes defense systems costly and causes their repeated loss [32].”

“These differences are consistent with the differences in the lifestyles be-tween these selfish elements whereby transposons and plasmids are relatively harmless to the host cell, apart from being an energetic burden, whereas prophages have the potential to kill the host upon lisogenization (20, 54).”

“Besides the acquisition of novel genes, HGT also provides means for recombination and helps avoid collapse of the population due to mutational meltdown (Muller’s ratchet process) (Lynch et al., 1993; Gordo et al., 2002; Iranzo et al., 2016).”

“The presence of an antiviral system in every living organism further supports the global distribution of viruses [9], although their biological roles go beyond pathogenicity [10].”

“This evolutionary mechanism, known as Muller’s ratchet, appears to be the typical fate of pathogens that thrive on complex infection cycles, including intracellular parasitism (Iranzo et al., 2016; Moran, 1996), that experience frequent population bottlenecks.”

“Based on the observation that bacterial genomes are inevitably parasitized by mobile genetic elements (MGEs) (33, 34), they argue that transformation Carvalho et al.”

“The widespread presence of parasites in both artificial and natural communities suggests that they are a universal outcome of the evolution of complex adaptive systems [330–332].”

“Although transformation is not ubiquitous across bacteria [71], the necessity for mechanisms blocking the integration of parasitic mobile elements is widespread [86, 87].”

“Because transfer and carriage of MGEs have been usually assumed to be costly, they are often considered genetic parasites of bacteria [87].”

“All prokaryotes are parasitized by viruses (known as phages, in the case of bacteria) including those bacteria and archaea that are replete with innate and adaptive defense systems.[26,27] The life cycle of tem-”

“Plasmids are generally considered parasitic elements [29,30].”

“It has been estimated that even the low levels of HGT required to avoid Muller’s ratchet are sufficient for selfish MGEs to persist (Iranzo et al. 2016; Van Dijk et al. 2020).”

“Parasitic replicators are reported to be inevitable in self-replicators with a certain level of complexity [40] as shown by the appearance of parasitic replicators soon after the initiation of replication in our translation-coupled RNA or DNA replication systems [29, 41].”

“Parasites would multiply at the expense of the products of the network without contributing to their generation, as it is shown in some theoretical studies (Iranzo et al., 2016; Koonin et al., 2017).”

“T emperate bacteriophages are common, and their prevalence is reflected in the abundance of prophages in sequenced bacterial genomes (1, 2).”

“The emergence of genetic parasites is unavoidable [79,80].”

“The diversity of virus genome architectures with their frequent modular organization (Iranzo et al, 2016a), high mutation rates (Peck and Lauring, 2018), positive selection (Daugherty and Malik, 2012), and dependency on host cells, drive viruses to evolve faster than cellular organisms.”

“Moreover, this has also given us a glimpse into our own past, as every biologic replication system with appreciable complexity co-evolves with parasites and at the same time develops mechanisms of resistance to them (3, 4).”

“However, it comes to reason that any self-replicating system, however rudimentary, is subject to the emergence of parasites [97, 98], of non-cooperative defectors that use system’s resources for their sole benefit.”

“Viruses are ubiquitous parasites of cellular life and the most abundant biological entities on earth, predicted to appear in any replicator system (Koonin and Dolja 2013; Iranzo et al. 2016; Krupovic, Dolja, and Koonin 2019).”

“If there are ways in which plasmid DNAs can survive within cells without any phe-notypiceffects,thenplasmidswhoseonly “ function ” isself-preservationwill inevitably arise and be maintained by what we call “ non-phenotypic selection ” 12,29,30 .”

“the evolution of genomes with integrated MGE, combined with probabilistic reconstruction of the evolution of bacterial and archaeal genomes, suggest that horizontal gene transfer at rates that are required to stave off the mutational meltdown of microbial populations (Muller’s ratchet) prevents elimination of genetic…”

“Along with cognition [24], parasites have been proposed as causal agents that boost biological complexity, grounded in a plethora of studies, particularly regarding viruses [25–27].”

“…proper RNA helicase activity, as well as any active proofreading ability, long constructs might be more prone to dsRNA-formation, and/or accumulation of deleterious mutations, eventually leading to the loss of the replication ability (Iranzo et al., 2016; Kun et al., 2015; Tomita et al., 2015).”

“Arguably the emergence and persistence of parasites is unavoidable, since parasite-free states are evolutionary unstable, and microbial populations cannot simultaneously clear parasites yet escape extinction through Muller’s ratchet [8, 9].”

“…been considered a critical obstacle for primitive self-replicators to overcome before the emergence of life, as parasites inevit-ably arise in self-replicating systems (Iranzo et al. 2016) and disrupt interdependent or cooperative replication networks (Eigen and Schuster 1978; Maynard Smith 1979).”

“Together with the previous analyses indicating that genetic parasites could 408 not be purged from prokaryote populations due to the high rate of horizontal gene transfer that is essential to 409 the survival of these populations [39, 40], the present results support the concept of genetic parasites as an 410 intrinsi…”

“Since parasites inevitably appear in systems above a certain complexity [38,39], they could have played a pivotal role for continuous evolution and diversification of primitive replication systems that approached more complex cellular organisms.”

“According to Iranzo et al. (2016), they act as parasites because they use cellular energy for their synthesis.”

“Genetic parasites were likely unavoidable in early replicator systems, particularly before stable cellular boundaries emerged and horizontal transfer between protocells was frequent (Iranzo et al. 2016).”