Genetic diversity: frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats.
Frameshift mutations provide recognized mechanisms for changing the coding potential of an organism. Here, multiple frameshifts are identified in repetitive sequences within an Epstein-Barr virus unspliced early gene, LF3, which is associated with the viral replicative cycle and also transcriptionally expressed in many virally associated tumors. On the DNA strand encoding LF3, there are three open reading frames, only one of which contains an initiation codon. Most (>95%) of the gene consists of numerous (>20, varying with cell source) GC-rich copies of a 102-bp direct repeat (called IR 4) flanked by small unique sequences. LF3 may express a protein if its initiation and termination codons reside in the same reading frame, but this is not always the case. Frameshifting events, occurring in short runs of pyrimidines (mainly C residues) in the repeats, give rise to mutations which may provide a mechanism for escape of an LF3 function from host surveillance. Sequence studies link these frameshifts to DNA replication errors. Notably, the number of sites in LF3 at which such mutations can occur permits a very large amount of diversity in this gene. Our data also suggest a second degeneracy mechanism within the protein itself, which influences its stability and may reflect a host defense mechanism. LF3 thus provides a potentially important model for studying the quest for supremacy between a virus and its host.
Xue
Shao-An
SA
Viral Oncology Unit, Division of Medicine, Wright-Fleming Institute, Imperial College of Science, Technology and Medicine at St. Mary's, Norfolk Place, London W2 1PG, UK.
Jones
M D
MD
Lu
Qi-Long
QL
Middeldorp
J M
JM
Griffin
Beverly E
BE
D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology / Q000821:virology; D002277:Carcinoma / Q000473:pathology / Q000821:virology; D002461:Cell Line, Transformed; D003062:Codon / Q000235:genetics; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology; D016368:Frameshift Mutation; D005814:Genes, Viral; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007244:Infectious Mononucleosis / Q000473:pathology / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology; D016366:Open Reading Frames; D012091:Repetitive Sequences, Nucleic Acid; D012641:Selection, Genetic; D016415:Sequence Alignment; D019139:Tumor Escape; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D003062:Codon; D004279:DNA, Viral; C473028:LF3 protein, Epstein-Barr virus; D014764:Viral Proteins; D015678:Viral Structural Proteins