Retraction and Corrections RETRACTION CORRECTIONS PROFILE EVOLUTION Retraction for ‘‘Profile of Phillip Cohen,’’ by Carrie Arnold, Correction for ‘‘Origin, antiviral function and evidence for which appeared in issue 12, March 24, 2009, of Proc Natl Acad positive selection of the gammaretrovirus restriction gene Fv1 in Sci USA (106:4581–4583; first published March 17, 2009; the genus Mus,’’ by Yuhe Yan, Alicia Buckler-White, Kurt 10.1073/pnas.0902168106). Wollenberg, and Christine A. Kozak, which appeared in issue 9, The editors wish to note that because of several factual and March 3, 2009, of Proc Natl Acad Sci USA (106:3259–3263; first typographical errors we are retracting this article. A corrected published February 12, 2009; 10.1073͞pnas.0900181106). version will be published in a subsequent issue. The PNAS The authors note that due to a printer’s error, the database editors deeply regret the errors. accession numbers in the footnote on page 3259 appeared ͞ ͞ ͞ ͞ incorrectly. The footnote ‘‘Data deposition: The sequences www.pnas.org cgi doi 10.1073 pnas.0903490106 reported in this paper have been deposited in the GenBank database (accession nos. X97719, FJ603554, and X97720),’’ should instead have appeared as: ‘‘Data deposition: The se- quences reported in this paper have been deposited in the GenBank database (accession nos. FJ603554–FJ603574).’’ Ad- ditionally, on page 3259, left column, the first line of the third full paragraph, ‘‘Fv1 was cloned and identified as a coopted ERV sequence that is related to the gag gene of MuERV-L (3, 4), a Class III (spumavirus-related) ERV transposit family that is transpositionally active in mice but has no known infectious virus counterparts,’’ should instead have appeared as ‘‘Fv1 was cloned and identified as a coopted ERV sequence that is related to the gag gene of MuERV-L (3, 4), a Class III (spumavirus-related) ERV family that is transpositionally active in mice but has no known infectious virus counterparts.’’ These errors do not affect the conclusions of the article. www.pnas.org͞cgi͞doi͞10.1073͞pnas.0901885106 MEDICAL SCIENCES Correction for ‘‘A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportu- nities,’’ by Katherine S. Garman, Chaitanya R. Acharya, Elena Edelman, Marian Grade, Jochen Gaedcke, Shivani Sud, William Barry, Anna Mae Diehl, Dawn Provenzale, Geoffrey S. Gins- burg, B. Michael Ghadimi, Thomas Ried, Joseph R. Nevins, Sayan Mukherjee, David Hsu, and Anil Potti, which appeared in issue 49, December 9, 2008, of Proc Natl Acad Sci USA (105:19432–19437; first published December 2, 2008; 10.1073͞ pnas.0806674105). The authors note that the term ‘‘prognostic score’’ should be substituted for the term ‘‘Recurrence Score,’’ which is a regis- tered trademark of Genomic Health and is not associated in any way with the authors or the article. The online version of the article has been corrected accordingly as of April 7, 2009. www.pnas.org͞cgi͞doi͞10.1073͞pnas.0902004106 6878 ͉ PNAS ͉ April 21, 2009 ͉ vol. 106 ͉ no. 16 www.pnas.org Downloaded by guest on September 24, 2021 Origin, antiviral function and evidence for positive selection of the gammaretrovirus restriction gene Fv1 in the genus Mus Yuhe Yana, Alicia Buckler-Whitea, Kurt Wollenbergb, and Christine A. Kozaka,1 aLaboratory of Molecular Microbiology, bBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0460 Communicated by Malcolm A. Martin, National Institutes of Health, Bethesda, MD, January 7, 2009 (received for review November 17, 2008) The Fv1 virus resistance gene is a coopted endogenous retrovirus reverse transcription and before integration. Fv1 is known to (ERV) sequence related to the gag gene of the MuERV-L ERV family. target the virus capsid gene; a single amino acid substitution at Three major Fv1 resistance alleles have been identified in labora- position 110 distinguishes N- and B-tropic viruses (7), and tory mice, and they target virus capsid genes to produce charac- substitutions at additional residues in the capsid N-terminal teristic patterns of resistance to mouse leukemia viruses (MLVs). domain are responsible for NR- and NB-tropism (5, 8). We identified Fv1 in 3 of the 4 Mus subgenera; its absence from Until recently, Fv1-type restriction had only been identified in Coelomys and 1 of 3 species of Pyromys indicate Fv1 was acquired laboratory mice and wild mouse species closely related to shortly after the origin of the Mus genus. We sequenced Fv1 genes laboratory mice (2). Our examination of an African pygmy from 21 mice representative of the major taxonomic groups of mouse, subgenus Nannomys, identified an unusual postentry Mus. Two lines of evidence indicate that Fv1 has had antiviral resistance to ecotropic MuLVs (9). Although this resistance function for 7 million years of evolution. First, 2 species of African targets some of the same amino acid residues as the mouse Fv1 pygmy mice (subgenus Nannomys) show an Fv1-like MLV resis- gene, the pattern of virus resistance in the pygmy mouse cells tance, and transduced cells expressing the Nannomys Fv1 gene does not resemble that attributed to any of the laboratory mouse reproduce this resistance pattern. Second, sequence comparisons EVOLUTION suggest that Fv1 has been involved in genetic conflicts throughout Fv1 alleles. Mus evolution. We found evidence for strong positive selection of We have now screened additional Mus species distantly related Fv1 and identified 6 codons that show evidence of positive selec- to laboratory strains for Fv1-like resistance phenotypes, and tion: 3 codons in the C-terminal region including 2 previously analyzed the Fv1 sequence in wild mouse species of 3 Mus shown to contribute to Fv1 restriction in laboratory mice, and 3 subgenera. We show here that the pygmy mouse Fv1 has antiviral codons in a 10-codon segment overlapping the major homology activity and demonstrate that Fv1 has been under strong positive region of Fv1; this segment is known to be involved in capsid selection throughout 7 MY of Mus evolution. We identified 6 multimerization. This analysis suggests that Fv1 has had an anti- codons under strong positive selection including 2 residues viral role throughout Mus evolution predating exposure of mice to implicated in Fv1-mediated virus restriction, and 3 codons in a the MLVs restricted by laboratory mouse Fv1, and suggests a segment overlapping the Fv1 major homology region (MHR) mechanism for Fv1 restriction. region, a region that in retroviruses produces the interface for capsid binding and dimerization. Fv1 gammaretrovirus restriction gene ͉ mouse endogenous retrovirus ͉ Mus evolution Results Analysis of the 4 Subgenera of Mus for Fv1. We examined repre- ild mouse species and inbred laboratory strains vary in sentative species of all 4 Mus subgenera (Mus, Pyromys, Nanno- Wtheir susceptibility to gammaretrovirus infection, and mys and Coelomys) for Fv1 sequences by Southern blot analysis such resistance can be due to constitutively expressed antiviral using a probe from the 5Ј end of Fv1 (Fig. 1A). One Fv1-reactive factors that target various stages of the retroviral life cycle. The band was detected in most species; Mus mus caroli has 2 prototype for such virus resistance factors is the Fv1 gene, BglI-generated Fv1-related copies (Fig. 1B). Fv1 was identified discovered 40 years ago in studies on resistance to Friend murine in3ofthe4Mus subgenera; it was missing in Mus coelomys pahari leukemia virus (MLV) (1). and in Mus pyromys shortridgei,1of3Pyromys species tested. There are 4 well characterized functional variants of Fv1 and PCR using primers designed to amplify the 3Ј end of Fv1 along additional Fv1-like restrictions found in inbred strains and wild with flanking sequences confirmed the absence of Fv1 from n b mouse species (2). Three of these alleles, termed Fv1 , Fv1 , and these 2 species (Fig. 1C). These primers also distinguish the 2 nr Fv1 , produce characteristic patterns of resistance to subgroups major Fv1 variants found in laboratory mouse strains; Fv1n has of mouse-tropic viruses that are designated N-, B-, or NR-tropic. a 1.3-kb deletion at its 3Ј end relative to Fv1b. Both Fv1 variants 0 Cells with the Fv1 (null) allele restrict none of these virus were identified in Mus species. Most mice carry the 1.3-kb subgroups, and NB-tropic viruses are not restricted by any of segment characteristic of Fv1b; the Fv1n deletion was found only Fv1 these alleles. in house mouse species, specifically all 4 Mus mus musculus Fv1 was cloned and identified as a coopted ERV sequence that is related to the gag gene of MuERV-L (3, 4), a Class III (spumavirus-related) ERV transposit family that is transposi- Author contributions: C.A.K. designed research; Y.Y. and A.B.-W. performed research; tionally active in mice but has no known infectious virus coun- A.B.-W. and K.W. analyzed data; and C.A.K. wrote the paper. terparts. The major resistance variants of Fv1 differ from one The authors declare no conflict of interest. b another at 3 amino acid sites in its C-terminal region, and Fv1 Data deposition: The sequences reported in this paper have been deposited in the GenBank n nr additionally differs from Fv1 and Fv1 at its C terminus due to database (accession nos. X97719, FJ603554, and X97720). a 1.3-kb indel (3). Substitutions at the 3 sites and variation at the 1To whom correspondence should be addressed. E-mail: [email protected]. C terminus all contribute to resistance (5, 6). The mechanism of This article contains supporting information online at www.pnas.org/cgi/content/full/ resistance is unknown, but Fv1 typically blocks replication after 0900181106/DCSupplemental. www.pnas.org͞cgi͞doi͞10.1073͞pnas.0900181106 PNAS Early Edition ͉ 1of5 Fig.