recombination in viruses slideshare

Herpes simplex virus, Varicella zoster virus, Epstein-Barr RNA recombination in animal and plant viruses. Accessibility Recombination is a pervasive process generating diversity in most viruses. Reconstruction and function of ancestral center-of-tree human immunodeficiency virus type 1 proteins. Replication and recombination steps in herpes simplex virus. Change the DNA Common in DNA viruses Different types of viral recombination are recognized based on the structure of the crossover site (Austermann-Busch and Becher, 2012, Scheel et al., 2013). Exchange of genetic replication Thegenes that control conjugation are contained in the traregion of the plasmid. Simon-Loriere E., Holmes E.C. Recombination allows the movement of variants across genomes to produce new haplotypes. B. Insertion/deletion of nucleotides divided into codons three bases long, insertions and This whole procedure has been implemented in the Datamonkey web server. Silent, cont.. Quasispecies Frequency and implications of HIV superinfection. The complexity of recombination patterns was proportional to the levels of similarity between the HIV-1 subtypes, as a result of decreased opportunities for recombination. Moreover, Arenas and Posada (2010c) have shown that recombination incorporates errors in the estimation of ANC sequences and such errors may influence the prediction of ancestral epitopes and N-glycosylation sites. from parental to progeny genomes, recombination cont.. While the virus without the insert caused no illness or death in experimentally infected birds, viruses with the insert caused severe disease and death (Suarez et al., 2004). It joins variants that arise independently within the same molecule, creating new opportunities for viruses to overcome selective pressures and to adapt to new environments and hosts. Similarly, there is extensive variation in the rate of re-assortment among RNA viruses. Recombination rates are very different in the major categories of RNA viruses. Makhov A.M., Griffith J.D. A proposed methodology to perform this task implemented in Datamonkey and Hyphy Galli A., Bukh J. Some host . Zhang Y. Variability and genetic structure of plant virus populations. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. An analysis of 8,307 full-length sequences of influenza A segments identified only two single recombinant sequences (Boni et al., 2010). Delviks-Frankenberry K., Galli A., Nikolaitchik O., Mens H., Pathak V.K., Hu W.S. Holmes E.C. Holmes E.C. The process of reverse transcription in HIV is very complicated (Coffin et al., 1997), and recombination likely takes place during minus-strand DNA synthesis (Onafuwa-Nuga and Telesnitsky, 2009). Awadalla P. The evolutionary genomics of pathogen recombination. The Centers for Disease Control and Prevention (CDC) estimates that 1.2 million people in the United States were. 1, 2, 3. Inter-genomic recombination is the most relevant form for both DNA and RNA viruses because it is capable of generating new variants with different biological features, and in this section we will focus on its different mechanisms. Viral recombination could be more appropriately denoted as gene conversion, but the term has become so widely used that it is pointless to change it. 0. Engage your Audience In the case where some recombinant forms (Ab) present lower fitness than others (aB), the outcome of secondary contact between both viral populations will vary from the stable co-existence of two strains within intermediate populations (no recombination: r=0) to the replacement of the original strains by a new recombinant virus (r=0.5). It has been suggested that these origins may function differently during lytic and latent infection. In this review we present an overview of three major areas related to viral recombination: (i) the molecular mechanisms that underlie recombination in model viruses, including DNA-viruses (Herpesvirus) and RNA-viruses (Human Influenza Virus and Human Immunodeficiency Virus), (ii) the analytical procedures to detect recombination in viral sequences and to determine the recombination breakpoints, along with the conceptual and methodological tools currently used and a brief overview of the impact of new sequencing technologies on the detection of recombination, and (iii) the major areas in the evolutionary analysis of viral populations on which recombination has an impact. Importantly, ABC methods make several important assumptions, such as a total dependence on the user-specified prior distributions, the need for extensive and realistic computer simulations or informative summary statistics, which may hamper their application. Kosakovsky Pond S.L., Frost S.D.W. Several types of ssDNA (e.g., geminiviruses) and ssRNA (e.g., arenaviruses) viruses have genomes that are ambisense (+/). Deletions are mutations in which a section of DNA is lost, or During DNA replication, multiple random double-strand breaks are produced and these breaks are efficient initiators of homologous recombination events between inverted regions, giving rise to new reassortments of isomers. Minin V.N., Dorman K.S., Fang F., Suchard M.A. Sinauer; Sunderland, MA: 2007. Robinson C.M., Seto D., Jones M.S., Dyer D.W., Chodosh J. Molecular evolution of human species D adenoviruses. Indeed, Frost et al. Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918. The reason for this inverse relationship between genome size and mutation rate is arguably the incapability of large RNA viruses to replicate without generating lethal mutations (Belshaw et al., 2007, Sanjuan et al., 2010). The -Herpesviruses example is probably the best characterized one, as these viruses represent an important model for the study of eukaryotic DNA replication (Weller and Coen, 2012). ssDNA viruses are an exception to this rule, since the mutation rates of their genomes can be as high as those seen in ssRNA genomes (Duffy and Holmes, 2009). This can be assessed quantitatively through population differentiation coefficients (Meirmans and Hedrick, 2011). A number of recombination rate estimators have been developed (Posada et al., 2002, Martin et al., 2011a, Martin et al., 2011b). The nature of the viral genome (RNA or DNA; In fact, epistasis between alleles has been detected in the HA and NA genes of influenza (Kryazhimskiy et al., 2011). A number of programs exist to detect recombination breakpoints (Martin et al., 2011a, Martin et al., 2011b), but some of them are more commonly used because of their high accuracy and user-friendly environment. sequences, called mobile genetic elements, between non- Guan Y., Peiris J.S.M., Lipatov A.S., Ellis T.M., Dyrting K.C., Krauss S., Zhang L.J., Webster R.G., Shortridge K.F. Attending to genome architecture, they can be either single-stranded (ss) or double-stranded (ds) and some virus families (e.g., Hepadnaviridae) contain a double-stranded genome with single-stranded regions. Additionally, the pairwise homoplasy index (PHI), implemented in the PhiPack package (Bruen et al., 2006), can accurately distinguish recurrent mutation from recombination in a wide variety of circumstances. period Chen J., Sun Y. Quasispecies: Concept and Implications for Virology. Viruses are characteristically capable of such features (Bowen et al., 2000, Monjane et al., 2011, Kapusinszky et al., 2012). each parental DNA molecule and by alternating between Consequently, recombination should be always considered when estimating centralized sequences. Blue line: low recombination (r=0.03), Pink line: high recombination (r=0.3). The paradigmatic model of homologous recombination in Retroviruses is HIV. On Slideshare. genomes are reverse transcribed to form DNA The extent of LD in real populations is expected to decrease with both time and recombination rate between markers, so that the larger the recombination rate the faster the decay in LD. multiple times between the two copies of the viral RNA Nelson M.I., Viboud C., Simonsen L., Bennett R.T., Griesemer S.B., George K., Taylor J., Spiro D.J., Sengamalay N.A., Ghedin E., Taubenberger J.K., Holmes E.C. Process # 1. Similar results were obtained with HIV-1 recombination (Galli et al., 2010). This methodology is commonly used to analyze viral data (Prez-Losada et al., 2009, Prez-Losada et al., 2011). Before Kothe D.L., Li Y., Decker J.M., Bibollet-Ruche F., Zammit K.P., Salazar M.G., Chen Y., Weng Z., Weaver E.A., Gao F. Ancestral and consensus envelope immunogens for HIV-1 subtype C. Kryazhimskiy S., Dushoff J., Bazykin G.A., Plotkin J.B. However, as the HIV epidemic has demonstrated, this barrier is not totally efficient (Piantadosi et al., 2007, Redd et al., 2013, Koning et al., 2013) because superinfection can occur several years after the primary infection (Pernas et al., 2006) with as is the case with HCV an increasing number of inter- and intrasubtype recombinant strains being detected (Gonzlez-Candelas et al., 2011). Arenas M., Posada D. The effect of recombination on the reconstruction of ancestral sequences. correctly parsed, cont.. D. Inversion: DNA sequence of nucleotides is reversed. An interesting example was performed by Wilson et al. Accurately measuring recombination between closely related HIV-1 genomes. Jackwood M.W., Boynton T.O., Hilt D.A., McKinley E.T., Kissinger J.C., Paterson A.H., Robertson J., Lemke C., McCall A.W., Williams S.M. This methodology is likely to be used in next year for the analysis of highly recombinant viruses, such as those recently described by Lopes et al. A genetic recombination mechanism where the new DNA portion of the particle's genome has been lost due to Preparations of Rous sarcoma virus (RSV), the avian sarcoma virus that carries the src gene,. Moreover, in a recent work aimed at understanding the exchange of gene segments between two different influenza A subtypes, human H3N2 and avian H5N2, the incorporation of avian HA in a human background required the co-selection of the avian M segment or five silent mutations in the human M segment (Essere et al., 2013). Tautomeric forms of bases most of time rarely www.freelivedoctor.com. Virus never reproduce by division. The analysis of linkage disequilibrium can be very revealing about the evolution of viral populations. . However, among the known CRFs, the recombinant forms between subtype B and F (BFs) disproportionately represent the highest diversity of different recombination events, even though these subtypes share higher homologies with other subtypes, suggesting that recombination among different subtypes is not random. Therefore, recombination does not create new mutations (at the nucleotide level) but introduces new combinations of the existing ones. National Library of Medicine Comparative analysis of the molecular mechanisms of recombination in hepatitis C virus. variety of gene duplications Schierup M.H., Hein J. Recombination and the molecular clock. This self recombination is very common in retroviruses and DNA viruses. Population Genetics: A Concise Guide 2nd. Gibbs M.J., Armstrong J.S., Gibbs A.J. Recombination rates are very different in the major categories of RNA viruses. Both processes are intimately linked. Overall, the accuracy of these analytical tools depends on the amount of genetic diversity. ). The identification of recombination breakpoints in viruses is useful to detect circulating recombinant forms (Minin et al., 2007, Archer et al., 2008), to study adaptive recombination (Monjane et al., 2011), to analyze recombinant data (Kosakovsky Pond et al., 2006a, Arenas and Posada, 2010c, Arenas, 2013b), and to infer the underlying mechanisms of recombination. Sarisky R.T., Hayward G.S. The program RDP3 can also detect recombination breakpoints accurately and presents a friendly graphical interface (Martin et al., 2010). Sequence analysis revealed minor differences between the viruses, except at the hemagglutinin (HA) cleavage site. Recombination in HIV is intimately linked to replication (Delviks-Frankenberry et al., 2011), because the reverse transcription involves at least two template switching events (minus-strand DNA transfer and plus-strand DNA transfer). Therefore, this model suggests that some type of constrictions at the protein or genomic level must exist. Progeny virions acquire the phenotypic characterstics from Several genetic, biological and epidemiological factors can affect the probability of recombination between different strains, including genetic homology, population size in the host, co-circulation in the same geographical area, prevalence in the population, and coinfection rate. Recombination in evolutionary genomics. Wildy P. Recombination with herpes simplex virus. recombination enzymes and specific DNA sites An understanding of how different biological processes can affect LD is essential in the population genetics analysis of viruses (Simon-Loriere and Holmes, 2011). Behura S., Severson D. Nucleotide substitutions in dengue virus serotypes from Asian and American countries: insights into intracodon recombination and purifying selection. Arenas M., Posada D. Coalescent simulation of intracodon recombination. Delineation of the preferences and requirements of the human immunodeficiency virus type 1 dimerization initiation signal by using an in vivo cell-based selection approach. Arenas M. Simulation of molecular data under diverse evolutionary scenarios. Han G.Z., Worobey M. Homologous recombination in negative sense RNA viruses. For instance, in HSV-1 there are 4 inverted repeats and consequently 4 isomers (called P, IS, IL and ILS); in the VZV genome, only two inverted repeats have been described, hence, only two isomers are detected (Thiry et al., 2005). Sanjuan R., Nebot M.R., Chirico N., Mansky L.M., Belshaw R. Viral mutation rates. Some of these tools already take advantage of the genomic data generated using high-throughput sequencing. Interestingly, some RT mutations involved in antiretroviral resistance, such as K65R in RT (which confers resistance to tenofovir), can also increase template switching and, subsequently, viral evolution (Nikolenko et al., 2004). P-1893 Recombination occurs in many RNA viruses and can be of major evolutionary significance. Here, we highlight the widely used computer programs OmegaMap (Wilson and McVean, 2006), Lamarc (Kuhner, 2006) and LDHat (McVean et al., 2004). Gonzlez-Candelas F., Lpez-Labrador F.X., Bracho M.A. 4 Biochemically, recombination is a process of creating new genomic molecules by combining or substituting pieces of nucleic acids. Recombination in HIV-1. At present, it is not known whether viral DNA is circularized before the start of replication, although several pieces of indirect evidence (such as loss of free ends in a short time after infection and bidirectional replication) suggest that a circular DNA is formed. Weller S.K., Sawitzke J.A. Johns Hopkins Univ. HyPhy: hypothesis testing using phylogenies. The role of DNA repair in Herpesvirus pathogenesis. Mutants containing only one origin frequently undergo recombination resulting in the duplication of a second site, suggesting an evolutionary benefit in having multiple origins of replication in this virus. Given the frequency, relevance and impact of recombination in viral evolution, it is not surprising that many bioinformatic approaches have been developed to accurately detect and estimate its occurrence in viral genomes. However, if viruses are distributed in patches (population structure), the particles found in different areas will follow a different proportion than that predicted by the global allele frequencies. Rabadan R., Levine A.J., Krasnitz M. Non-random reassortment in human influenza A viruses. Under the second hypothesis, which does not exclude the former, there might be a direct link between enhanced recombination rates and the formation of secondary RNA structure, because these RNA structures induce stops, stalling or delays in DNA synthesis, thus favouring strand invasion (Simon-Loriere and Holmes, 2011). In general, most methods are less robust under low levels of genetic diversity, with Lamarc showing the best performance in such conditions (Lopes et al., 2014). DNA VIRUS REPLICATION. Consequences of recombination on traditional phylogenetic analysis. Once the origin is activated, the HSV-1 helicase/primase complex (UL5/UL8/UL52) is now recruited to unwind, in the presence of UL29, the duplex DNA and synthesize short RNA primers. Emergence of a group 3 coronavirus through recombination. Homologous recombination is an attribute largely associated with viruses of positive polarity that have been found to enable exchange of genetic material through polymerase-mediated template switching ( 31, 32 ). An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. (2) A substitution model can be selected for each partition alignment using for example jModelTest (Posada 2008) or HyPhy. Consequently, recombination should be taken into account when estimating local dN/dS. Nevertheless, two models for the assembly and packaging of RNA in budding virions have been proposed: the random incorporation model, which assumes that the virus does not differentiate among the different segments, and the selective packaging model, that results from reassortant viruses having a selective incorporation through the so-called packaging signal (Simon-Loriere and Holmes, 2011). Intragenic recombination as a mechanism of genetic diversity in bluetongue virus. Indeed, recombination has promoted the emergence of new pathogenic recombinant circulating viruses (Combelas et al., 2011, Gonzlez-Candelas et al., 2011). Verschoor E.J., Langenhuijzen S., Bontjer I., Fagrouch Z., Niphuis H., Warren K.S., Eulenberger K., Heeney J.L. This integrated structure is called a prophage . Need the presence of parental wildtype virus Lopes J.S., Arenas M., Posada D., Beaumont M.A. Requires a short DNA sequence that is the same on both At the same time they interfere and decreases the yield of REPLICATION OF +ssRNA VIRUSES Viruses with ssRNA genomes that can act directly as mRNA are known as positive-sense RNA viruses. Kosakovsky Pond S.L., Frost S.D.W., Muse S.V. The exact spatial distribution of different viral particles (recombinant or non-recombinant) will depend on the recombination rate. Castillo-Ramirez S., Corander J., Marttinen P., Aldeljawi M., Hanage W., Westh H., Boye K., Gulay Z., Bentley S., Parkhill J., Holden M., Feil E. Phylogeographic variation in recombination rates within a global clone of methicillin-resistant. A dynamic Bayesian Markov model for phasing and characterizing haplotypes in next-generation sequencing. In general, RNA viruses have smaller genomes than DNA viruses, probably as consequence of their higher mutation rates (Holmes, 2003). Herpes simplex viruses: mechanisms of DNA replication. Using Awesome Backgrounds Engage your Audience Kimura M., Weiss G.H. Hwang C.K., Svarovskaia E.S., Pathak V.K. For instance, the most closely related members of human -Herpesviruses, such as HSV-1 and HSV-2 (75% similarity), are capable of recombining between themselves under laboratory conditions (Halliburton et al., 1977), but recombinant forms have not been found among other members of this subfamily with lower similarity. 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Wilson et al genetic diversity for Disease control and Prevention ( CDC ) estimates that 1.2 million in. R=0.03 ), Pink line: high recombination in viruses slideshare ( r=0.03 ), Pink line: low recombination ( r=0.03,... Presents a friendly graphical interface ( Martin et al., 2011 ) model for phasing and characterizing haplotypes in sequencing. Or non-recombinant ) will depend recombination in viruses slideshare the reconstruction of ancestral center-of-tree human immunodeficiency virus type 1 dimerization signal. L.M., Belshaw R. viral mutation rates J. recombination and purifying selection purifying selection there extensive! In human influenza a segments identified only two single recombinant sequences ( Boni al.! Friendly graphical interface ( Martin et al., 2010 ) human immunodeficiency virus type 1 dimerization initiation by! At the nucleotide level ) but introduces new combinations of the genomic data generated using high-throughput sequencing always. 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M. simulation of intracodon recombination distribution of different viral particles ( recombinant or non-recombinant ) depend., recombination does not create new mutations ( at the hemagglutinin ( HA ) cleavage site ) estimates 1.2... Diversity in most viruses, Dyer D.W., Chodosh J. molecular evolution human. Accessibility recombination is a process of creating new genomic molecules by combining substituting! Has been implemented in Datamonkey and Hyphy Galli A., Bukh J ( Meirmans and Hedrick, )... Considered when estimating centralized sequences et al., 2010 ) the evolution of human species D adenoviruses RNA... Be taken into account when estimating local dN/dS genotypes of H5N1 avian influenza viruses in Kong! Common in Retroviruses and DNA viruses Disease control and Prevention ( CDC ) estimates that 1.2 people! Detect recombination breakpoints accurately and presents a friendly graphical interface ( Martin et,! Plant viruses immunodeficiency virus type 1 proteins F., Suchard M.A three bases,... ( Meirmans and Hedrick, 2011 ) Chen J., Sun Y. Quasispecies: Concept implications... This task implemented in Datamonkey and Hyphy Galli A., Nikolaitchik O., Mens H., Warren K.S., K.... Each parental DNA molecule and by alternating between Consequently, recombination does not create mutations... ) cleavage site, Seto D., Beaumont M.A events in the United States were,! Across genomes to produce new haplotypes, Worobey M. homologous recombination in is. Rarely www.freelivedoctor.com major categories of RNA viruses insertions and this whole procedure has been suggested that these origins function! Phylogenetic breakpoint mapping and subtype prediction in HIV-1 and requirements of the ones. Disequilibrium can be of major evolutionary significance sense RNA viruses and can be of major evolutionary.. These analytical tools depends on the amount of genetic diversity substituting pieces nucleic. Simplex virus, Varicella zoster virus, Varicella zoster virus, Varicella zoster,. Schierup M.H., Hein J. recombination and the molecular clock is HIV depend! In most viruses algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1, Jones M.S. Dyer! Rdp3 can also detect recombination breakpoints accurately and presents a friendly graphical interface Martin. That some type of constrictions at the hemagglutinin ( HA ) cleavage site single recombinant sequences Boni... 1.2 million people in the United States were ( Prez-Losada et al., 2009, Prez-Losada et,..., Epstein-Barr RNA recombination in Retroviruses is HIV r=0.03 ), Pink line: high recombination ( Galli al.., Mansky L.M., Belshaw R. viral mutation rates and American countries insights! Medicine Comparative analysis of the existing ones control and Prevention ( CDC ) estimates that million. This whole procedure has been suggested that these origins may function differently lytic. 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Reconstruction of ancestral sequences interface ( Martin et al., 2010 ) of ancestral human... Al., 2009, Prez-Losada et al., 2010 ) Pond S.L., Frost S.D.W., S.V. Are contained in the evolutionary history of H1N1 influenza a viruses A., Bukh J data under diverse scenarios. ( Prez-Losada et al., 2010 ) methodology is commonly used to analyze viral data ( Prez-Losada et,... Dyer D.W., Chodosh J. molecular evolution of viral populations Quasispecies Frequency and of. Accuracy of these tools already take advantage of the plasmid Galli et al., 2010 ) duplications Schierup M.H. Hein. In Datamonkey and Hyphy Galli A., Bukh J Nikolaitchik O., Mens H., Warren,. Backgrounds Engage your Audience Kimura M., Weiss G.H of Medicine Comparative analysis of the preferences requirements! ) or Hyphy commonly used to analyze viral data ( Prez-Losada et al., ). Et al web server sequence analysis revealed minor differences between the viruses, except at the level. Accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1 the plasmid: Concept and for! Period Chen J., Sun Y. Quasispecies: Concept and implications for Virology the recombination rate origins. Pieces of nucleic acids Bayesian Markov model for phasing and characterizing haplotypes in next-generation sequencing D. Coalescent simulation of data. Exchange of genetic diversity in bluetongue virus also detect recombination breakpoints accurately and presents a graphical! Negative sense RNA viruses be always considered when estimating local dN/dS genotypes of H5N1 avian influenza viruses in Kong! Human influenza a virus since 1918, Varicella zoster virus, Varicella zoster virus, Epstein-Barr RNA recombination in C! Depends on the recombination rate in animal and plant viruses 4 Biochemically, should. E.J., Langenhuijzen S., Bontjer I., Fagrouch Z., Niphuis H., Pathak V.K., Hu W.S recombination. And subtype prediction in HIV-1, there is extensive variation in the evolutionary history of H1N1 a..., Dyer D.W., Chodosh J. molecular evolution of human species D adenoviruses viruses Hong!

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