The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure

Shapiro, Maxwell; Meier, Stephen R.; MacCarthy, Thomas

doi:10.1186/s12859-018-2161-y

Cited by 14 publications

(21 citation statements)

References 34 publications

(29 reference statements)

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“…The quantification of AID and A3 hotspot representation in the gamma-herpesviruses was determined using the cytidine deaminase representation reporter (CDUR) (Shapiro, Meier, and MacCarthy 2018). This reporter consists of different shuffling algorithms that generate a null distribution of 1,000 random sequences from a subject sequence, and compares the number of hotspots in the sequence of interest to this null model.…”

Section: Methodsmentioning

confidence: 99%

Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses

et al. 2019

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The human gamma-herpesviruses, Epstein–Barr virus and Kaposi's sarcoma-associated herpesvirus, establish lifelong latency in B cells and are associated with multiple malignancies. Virus-host coevolution often drive changes in both host immunity and in the viral genome. We consider one host immune mechanism, the activation-induced deaminase (AID)/APOBEC family of cytidine deaminases, that induces mutations in viral DNA. AID, the ancestral gene in the family has a conserved role in somatic hypermutation, a key step in antibody affinity maturation. The APOBEC3 subfamily, of which there are seven genes in human, have evolved antiviral functions and have diversified in terms of their expression pattern, subcellular localization, and DNA mutation motifs (hotspots). In this study, we investigated how the human gamma-herpesviruses have evolved to avoid the action of the AID/APOBEC enzymes and determine if these enzymes are contributing to the ongoing evolution of the viruses. We used computational methods to evaluate observed versus expected frequency of AID/APOBEC hotspots in viral genomes and found that the viruses have evolved to limit the representation of AID and certain APOBEC3 motifs. At the same time, the remaining hotspots were highly likely to cause amino acid changes, suggesting prolonged evolutionary pressure of the enzymes on the viruses. To study current hypermutation, as opposed to historical mutation processes, we also analyzed putative mutations derived from alignments of published viral genomes and found again that AID and APOBEC3 appear to target the genome most frequently. New protein variants resulting from AID/APOBEC activity may have important consequences in health, including vaccine development (epitope evolution) and host immune evasion.

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Section: Methodsmentioning

confidence: 99%

Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses

et al. 2019

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“…Different bioinformatics approaches have been used to search for evidence of an A3 evolutionary footprint in viral genomes [17,[29][30][31][32][33]35,36]. In this study, we adapted and extended the Warren et al approach [29] to carry out a general screening for the A3 footprint of the genomes of all currently annotated human viruses.…”

Section: Plos Pathogensmentioning

confidence: 99%

“…The A3 footprint is defined as the under-representation of A3-targeted motifs. Different approaches have been devised to estimate the over/under-representation of a given motif [17,[29][30][31][32][33]35,36].…”

Section: Definition Of the A3 Footprintmentioning

confidence: 99%

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Footprint of the host restriction factors APOBEC3 on the genome of human viruses

et al. 2020

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APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5'TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint. The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APO-BEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted families; evidencing a selection pressure acting genome-wide and on both strands. Members of the parvoviridae family are differentially targeted in term of both magnitude and localization of the footprint. Interestingly, a massive APOBEC3 footprint is present on both strands of the B19 erythroparvovirus; making this viral genome one of the most cleaned sequences for APOBEC3-favored motifs. We also identified the endemic coronaviridae as significantly footprinted. Interestingly, no such footprint has been detected on the zoonotic MERS-CoV, SARS-CoV-1 and SARS-CoV-2 coronaviruses. In addition to viruses that are footprinted genome-wide, certain viruses are footprinted only on very short sections of their genome. That is the case for the gamma-herpesviridae and adenoviridae where the footprint is localized on the lytic origins of replication. A mild footprint can also be detected on the negative strand of the reverse transcribing HIV-1, HIV-2, HTLV-1 and HBV viruses. Together, our data illustrate the extent of the APOBEC3 selection pressure on the human viruses and identify new putatively APOBEC3-targeted viruses.

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“…Following publication of the original article [ 1 ], the authors reported that Figs. 1 and 3 were interchanged.…”

Section: Correctionmentioning

confidence: 99%

Correction to: The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure

2018

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The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure

Cited by 14 publications

References 34 publications

Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses

Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses

Footprint of the host restriction factors APOBEC3 on the genome of human viruses

Correction to: The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure

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