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Article: Adaptive evolution of Mus Apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate groove

TitleAdaptive evolution of Mus Apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate groove
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://pathogens.plosjournals.org/perlserv/?request=index-html&issn=1553-7374
Citation
Plos Pathogens, 2010, v. 6 n. 7, p. 1-14, e1000974 How to Cite?
AbstractMouse APOBEC3 (mA3) is a cytidine deaminase with antiviral activity. mA3 is linked to the Rfv3 virus resistance factor, a gene responsible for recovery from infection by Friend murine leukemia virus, and mA3 allelic variants differ in their ability to restrict mouse mammary tumor virus. We sequenced mA3 genes from 38 inbred strains and wild mouse species, and compared the mouse sequence and predicted structure with human APOBEC3G (hA3G). An inserted sequence was identified in the virus restrictive C57BL strain allele that disrupts a splice donor site. This insertion represents the long terminal repeat of the xenotropic mouse gammaretrovirus, and was acquired in Eurasian mice that harbor xenotropic retrovirus. This viral regulatory sequence does not alter splicing but is associated with elevated mA3 expression levels in spleens of laboratory and wild-derived mice. Analysis of Mus mA3 coding sequences produced evidence of positive selection and identified 10 codons with very high posterior probabilities of having evolved under positive selection. Six of these codons lie in two clusters in the N-terminal catalytically active cytidine deaminase domain (CDA), and 5 of those 6 codons are polymorphic in Rfv3 virus restrictive and nonrestrictive mice and align with hA3G CDA codons that are critical for deaminase activity. Homology models of mA3 indicate that the two selected codon clusters specify residues that are opposite each other along the predicted CDA active site groove, and that one cluster corresponds to an hAPOBEC substrate recognition loop. Substitutions at these clustered mA3 codons alter antiviral activity. This analysis suggests that mA3 has been under positive selection throughout Mus evolution, and identified an inserted retroviral regulatory sequence associated with enhanced expression in virus resistant mice and specific residues that modulate antiviral activity.
Persistent Identifierhttp://hdl.handle.net/10722/157606
ISSN
2015 Impact Factor: 7.003
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institute of Allergy and Infectious Diseases, NIH
Funding Information:

The work was supported by the Intramural Program of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorSanville, Ben_US
dc.contributor.authorDolan, MAen_US
dc.contributor.authorWollenberg, Ken_US
dc.contributor.authorYan, Yen_US
dc.contributor.authorMartin, Cen_US
dc.contributor.authorYeung, MLen_US
dc.contributor.authorStrebel, Ken_US
dc.contributor.authorBucklerWhite, Aen_US
dc.contributor.authorKozak, CAen_US
dc.date.accessioned2012-08-08T08:51:38Z-
dc.date.available2012-08-08T08:51:38Z-
dc.date.issued2010en_US
dc.identifier.citationPlos Pathogens, 2010, v. 6 n. 7, p. 1-14, e1000974en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://hdl.handle.net/10722/157606-
dc.description.abstractMouse APOBEC3 (mA3) is a cytidine deaminase with antiviral activity. mA3 is linked to the Rfv3 virus resistance factor, a gene responsible for recovery from infection by Friend murine leukemia virus, and mA3 allelic variants differ in their ability to restrict mouse mammary tumor virus. We sequenced mA3 genes from 38 inbred strains and wild mouse species, and compared the mouse sequence and predicted structure with human APOBEC3G (hA3G). An inserted sequence was identified in the virus restrictive C57BL strain allele that disrupts a splice donor site. This insertion represents the long terminal repeat of the xenotropic mouse gammaretrovirus, and was acquired in Eurasian mice that harbor xenotropic retrovirus. This viral regulatory sequence does not alter splicing but is associated with elevated mA3 expression levels in spleens of laboratory and wild-derived mice. Analysis of Mus mA3 coding sequences produced evidence of positive selection and identified 10 codons with very high posterior probabilities of having evolved under positive selection. Six of these codons lie in two clusters in the N-terminal catalytically active cytidine deaminase domain (CDA), and 5 of those 6 codons are polymorphic in Rfv3 virus restrictive and nonrestrictive mice and align with hA3G CDA codons that are critical for deaminase activity. Homology models of mA3 indicate that the two selected codon clusters specify residues that are opposite each other along the predicted CDA active site groove, and that one cluster corresponds to an hAPOBEC substrate recognition loop. Substitutions at these clustered mA3 codons alter antiviral activity. This analysis suggests that mA3 has been under positive selection throughout Mus evolution, and identified an inserted retroviral regulatory sequence associated with enhanced expression in virus resistant mice and specific residues that modulate antiviral activity.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://pathogens.plosjournals.org/perlserv/?request=index-html&issn=1553-7374en_US
dc.relation.ispartofPLoS Pathogensen_US
dc.subject.meshCytidine Deaminase - genetics-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals, Wild - genetics-
dc.subject.meshAnti-Retroviral Agents - chemistry-
dc.subject.meshEvolution, Molecular-
dc.titleAdaptive evolution of Mus Apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate grooveen_US
dc.typeArticleen_US
dc.identifier.emailYeung, ML: pmlyeung@hku.hken_US
dc.identifier.authorityYeung, ML=rp01402en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1371/journal.ppat.1000974en_US
dc.identifier.pmid20617165-
dc.identifier.pmcidPMC2895647-
dc.identifier.scopuseid_2-s2.0-77957656529en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957656529&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume6en_US
dc.identifier.issue7en_US
dc.identifier.spage1en_US
dc.identifier.epage14en_US
dc.identifier.isiWOS:000280527000008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridSanville, B=24765222800en_US
dc.identifier.scopusauthoridDolan, MA=7202585772en_US
dc.identifier.scopusauthoridWollenberg, K=35726354300en_US
dc.identifier.scopusauthoridYan, Y=8566170800en_US
dc.identifier.scopusauthoridMartin, C=16145532400en_US
dc.identifier.scopusauthoridYeung, ML=8350940900en_US
dc.identifier.scopusauthoridStrebel, K=7004482034en_US
dc.identifier.scopusauthoridBucklerWhite, A=7003902863en_US
dc.identifier.scopusauthoridKozak, CA=7102712967en_US
dc.customcontrol.immutablesml 130524-

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