Editing Genetic recombination (section)

==RNA virus recombination==

Numerous RNA viruses are capable of genetic recombination when at least two viral [[genome]]s are present in the same host cell.<ref name = Barr2010>{{cite journal | vauthors = Barr JN, Fearns R | title = How RNA viruses maintain their genome integrity | journal = The Journal of General Virology | volume = 91 | issue = Pt 6 | pages = 1373–87 | date = June 2010 | pmid = 20335491 | doi = 10.1099/vir.0.020818-0 | doi-access = free }}</ref><ref>{{Cite journal|last1=Simon-Loriere|first1=Etienne|last2=Holmes|first2=Edward C.|date=August 2011|title=Why do RNA viruses recombine?|journal=Nature Reviews Microbiology|language=en|volume=9|issue=8|pages=617–626|doi=10.1038/nrmicro2614|issn=1740-1526|pmc=3324781|pmid=21725337}}</ref> Recombination is largely responsible for RNA virus diversity and immune evasion.<ref name="Recombination is required for effic">{{cite journal | vauthors = Rawson JM, Nikolaitchik OA, Keele BF, Pathak VK, Hu WS | title = Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity | journal = Nucleic Acids Research | volume = 46 | issue = 20 | pages = 10535–10545 | date = November 2018 | pmid = 30307534 | pmc = 6237782 | doi = 10.1093/nar/gky910 }}</ref> RNA recombination appears to be a major driving force in determining genome architecture and the course of viral evolution among [[Picornavirus|picornaviridae]] ([[positive-sense single-stranded RNA virus|(+)ssRNA]]) (e.g. [[poliovirus]]).<ref name="pmid31540135">{{cite journal | vauthors = Muslin C, Mac Kain A, Bessaud M, Blondel B, Delpeyroux F | title = Recombination in Enteroviruses, a Multi-Step Modular Evolutionary Process | journal = Viruses | volume = 11 | issue = 9 | date = September 2019 | page = 859 | pmid = 31540135 | pmc = 6784155 | doi = 10.3390/v11090859 | doi-access = free }}</ref>  In the [[retrovirus|retroviridae]] ((+)ssRNA)(e.g. [[HIV]]), damage in the RNA genome appears to be avoided during [[reverse transcriptase|reverse transcription]] by strand switching, a form of recombination.<ref name="pmid1700865">{{cite journal | vauthors = Hu WS, Temin HM | title = Retroviral recombination and reverse transcription | journal = Science | volume = 250 | issue = 4985 | pages = 1227–33 | date = November 1990 | pmid = 1700865 | doi = 10.1126/science.1700865 | bibcode = 1990Sci...250.1227H }}</ref><ref name = Bernstein2018>{{cite journal | vauthors = Bernstein H, Bernstein C, Michod RE | title = Sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 57 | issue = | pages = 8–25 | date = January 2018 | pmid = 29111273 | doi = 10.1016/j.meegid.2017.10.024 | doi-access = free }}</ref>

Recombination also occurs in the [[reoviridae]] (dsRNA)(e.g. reovirus), [[orthomyxoviridae]] ((-)ssRNA)(e.g. [[influenza virus]])<ref name = Bernstein2018/> and [[coronaviridae]] ((+)ssRNA) (e.g. [[Severe acute respiratory syndrome|SARS]]).<ref name = Su2016>{{cite journal | vauthors = Su S, Wong G, Shi W, Liu J, Lai AC, Zhou J, Liu W, Bi Y, Gao GF | title = Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses | journal = Trends in Microbiology | volume = 24 | issue = 6 | pages = 490–502 | date = June 2016 | pmid = 27012512 | pmc = 7125511 | doi = 10.1016/j.tim.2016.03.003 }}</ref><ref name="Nikolaidis-2021">{{Cite journal|last1=Nikolaidis|first1=Marios|last2=Markoulatos|first2=Panayotis|last3=Van de Peer|first3=Yves|last4=Oliver|first4=Stephen G|last5=Amoutzias|first5=Grigorios D|date=2021-10-12|editor-last=Hepp|editor-first=Crystal|title=The neighborhood of the Spike gene is a hotspot for modular intertypic homologous and non-homologous recombination in Coronavirus genomes|url=https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msab292/6382323|journal=Molecular Biology and Evolution|volume=39|language=en|pages=msab292|doi=10.1093/molbev/msab292|pmid=34638137|pmc=8549283|issn=0737-4038}}</ref>

Recombination in RNA viruses appears to be an adaptation for coping with genome damage.<ref name="Barr2010" />  Switching between template strands during genome replication, referred to as copy-choice recombination, was originally proposed to explain the positive correlation of recombination events over short distances in organisms with a DNA genome (see first Figure, [[synthesis-dependent strand annealing|SDSA]] pathway).<ref>{{cite journal | vauthors = Bernstein H | title = On the mechanism of intragenic recombination. I. The rII region of bacteriophage T4. | journal = Journal of Theoretical Biology | date = 1962 | volume = 3 | issue = 3 | pages = 335–353 | doi = 10.1016/S0022-5193(62)80030-7 | bibcode = 1962JThBi...3..335B }}</ref>

Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans.<ref name="Su2016" />

Especially in coronaviruses, recombination may also occur even among distantly related evolutionary groups (subgenera), due to their characteristic transcription mechanism, that involves subgenomic mRNAs that are formed by template switching.<ref>{{Cite journal|last1=Graham|first1=Rachel L.|last2=Deming|first2=Damon J.|last3=Deming|first3=Meagan E.|last4=Yount|first4=Boyd L.|last5=Baric|first5=Ralph S.|date=December 2018|title=Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform|journal=Communications Biology|language=en|volume=1|issue=1|pages=179|doi=10.1038/s42003-018-0175-7|issn=2399-3642|pmc=6206136|pmid=30393776}}</ref><ref name="Nikolaidis-2021" />

When replicating its [[positive-sense single-stranded RNA virus|(+)ssRNA genome]], the [[poliovirus]] [[RNA-dependent RNA polymerase]] (RdRp) is able to carry out recombination.  Recombination appears to occur by a copy choice mechanism in which the RdRp switches (+)ssRNA templates during negative strand synthesis.<ref name="pmid3021340">{{cite journal | vauthors = Kirkegaard K, Baltimore D | title = The mechanism of RNA recombination in poliovirus | journal = Cell | volume = 47 | issue = 3 | pages = 433–43 | date = November 1986 | pmid = 3021340 | pmc = 7133339 | doi = 10.1016/0092-8674(86)90600-8 }}</ref>  Recombination by RdRp strand switching also occurs in the (+)ssRNA plant [[carmovirus]]es and [[tombusvirus]]es.<ref name="pmid14581540">{{cite journal | vauthors = Cheng CP, Nagy PD | title = Mechanism of RNA recombination in carmo- and tombusviruses: evidence for template switching by the RNA-dependent RNA polymerase in vitro | journal = Journal of Virology | volume = 77 | issue = 22 | pages = 12033–47 | date = November 2003 | pmid = 14581540 | pmc = 254248 | doi = 10.1128/jvi.77.22.12033-12047.2003 }}</ref>

Recombination appears to be a major driving force in determining genetic variability within coronaviruses, as well as the ability of coronavirus species to jump from one host to another and, infrequently, for the emergence of novel species, although the mechanism of recombination in is unclear.<ref name = Su2016/>
In early 2020, many genomic sequences of Australian SARS‐CoV‐2 isolates have deletions or mutations (29742G>A or 29742G>U; "G19A" or "G19U") in the s2m, suggesting that RNA recombination may have occurred in this RNA element.  29742G("G19"), 29744G("G21"), and 29751G("G28") were predicted as recombination hotspots.<ref>{{cite journal | vauthors = Yeh TY, Contreras GP | title = Emerging viral mutants in Australia suggest RNA recombination event in the SARS-CoV-2 genome | journal = The Medical Journal of Australia | volume = 213 | issue = 1 | pages = 44–44.e1 | date = July 2020 | pmid = 32506536 | pmc = 7300921 | doi = 10.5694/mja2.50657 }}</ref> During the first months of the COVID-19 pandemic, such a recombination event was suggested to have been a critical step in the evolution of SARS-CoV-2's ability to infect humans.<ref>{{cite bioRxiv| vauthors = Wang H, Pipes L, Nielsen R |date=2020-10-12|title=Synonymous mutations and the molecular evolution of SARS-Cov-2 origins|biorxiv=10.1101/2020.04.20.052019}}</ref> [[Linkage disequilibrium]] analysis confirmed that [[RNA recombination]] with the 11083G > T mutation also contributed to the increase of mutations among the viral progeny. The findings indicate that the 11083G > T mutation of SARS-CoV-2 spread during [[Diamond Princess (ship)|Diamond Princess]] shipboard quarantine and arose through de novo [[RNA recombination]] under positive selection pressure. In three patients on the [[Diamond Princess (ship)|''Diamond Princess'']] cruise, two mutations, 29736G > T and 29751G > T (G13 and G28) were located in [[Coronavirus 3′ stem-loop II-like motif (s2m)]] of SARS-CoV-2. Although s2m is considered an RNA motif highly conserved in 3' untranslated region among many coronavirus species, this result also suggests that s2m of SARS-CoV-2 is [[RNA recombination]]/mutation hotspot.<ref>{{cite journal | vauthors = Yeh TY, Contreras GP | title = Viral transmission and evolution dynamics of SARS-CoV-2 in shipboard quarantine | journal = Bull. World Health Organ. | volume = 99 | issue = 7 | pages = 486–495| date = 1 July 2021 | doi = 10.2471/BLT.20.255752 | pmid = 34248221 | pmc = 8243027 }}</ref>[[File:S2m structure of SARS-CoV.png|thumb|Schematic representation of the s2m RNA secondary structure, with tertiary structural interactions indicated as long range contacts.]] SARS-CoV-2's entire receptor binding motif appeared, based on preliminary observations, to have been introduced through recombination from coronaviruses of [[pangolin]]s.<ref name =  Li2020>{{cite journal | vauthors = Li X, Giorgi EE, Marichannegowda MH, Foley B, Xiao C, Kong XP, Chen Y, Gnanakaran S, Korber B, Gao F | title = Emergence of SARS-CoV-2 through recombination and strong purifying selection | journal = Science Advances | volume = 6 | issue = 27 | pages = eabb9153| date = July 2020 | pmid = 32937441 | pmc = 7458444 | doi = 10.1126/sciadv.abb9153  | bibcode = 2020SciA....6.9153L }}</ref>  However, more comprehensive analyses later refuted this suggestion and showed that SARS-CoV-2 likely evolved solely within bats and with little or no recombination.<ref>{{cite journal | vauthors = Boni MF, Lemey P, Jiang X, Lam TT, Perry BW, Castoe TA, Rambaut A, Robertson DL | display-authors = 6 | title = Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic | journal = Nature Microbiology | volume = 5 | issue = 11 | pages = 1408–1417 | date = November 2020 | pmid = 32724171 | doi = 10.1038/s41564-020-0771-4 | doi-access = free | hdl = 20.500.11820/222bb9b9-2481-4086-bd22-f0b200930bef | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Neches RY, McGee MD, Kyrpides NC | title = Recombination should not be an afterthought | journal = Nature Reviews. Microbiology | volume = 18 | issue = 11 | pages = 606 | date = November 2020 | pmid = 32958891 | pmc = 7503439 | doi = 10.1038/s41579-020-00451-1 }}</ref>