Genetic diversity: frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats

Shao-An Xue, M D Jones, Qi-Long Lu, J M Middeldorp, Beverly E Griffin

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2192-201
Number of pages10
JournalMolecular and Cellular Biology
Volume23
Issue number6
Publication statusPublished - Mar 2003

Cite this

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title = "Genetic diversity: frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats",
abstract = "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.",
keywords = "Amino Acid Sequence, Animals, Base Pairing, Base Sequence, Burkitt Lymphoma, Carcinoma, Cell Line, Transformed, Codon, DNA Replication, DNA, Viral, Epstein-Barr Virus Infections, Frameshift Mutation, Genes, Viral, Genetic Variation, Herpesvirus 4, Human, Humans, Infectious Mononucleosis, Mice, Mice, Nude, Molecular Sequence Data, Nasopharyngeal Neoplasms, Open Reading Frames, Repetitive Sequences, Nucleic Acid, Selection, Genetic, Sequence Alignment, Tumor Escape, Viral Proteins, Viral Structural Proteins, Journal Article",
author = "Shao-An Xue and Jones, {M D} and Qi-Long Lu and Middeldorp, {J M} and Griffin, {Beverly E}",
year = "2003",
month = "3",
language = "English",
volume = "23",
pages = "2192--201",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
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Genetic diversity : frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats. / Xue, Shao-An; Jones, M D; Lu, Qi-Long; Middeldorp, J M; Griffin, Beverly E.

In: Molecular and Cellular Biology, Vol. 23, No. 6, 03.2003, p. 2192-201.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genetic diversity

T2 - frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats

AU - Xue, Shao-An

AU - Jones, M D

AU - Lu, Qi-Long

AU - Middeldorp, J M

AU - Griffin, Beverly E

PY - 2003/3

Y1 - 2003/3

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Base Pairing

KW - Base Sequence

KW - Burkitt Lymphoma

KW - Carcinoma

KW - Cell Line, Transformed

KW - Codon

KW - DNA Replication

KW - DNA, Viral

KW - Epstein-Barr Virus Infections

KW - Frameshift Mutation

KW - Genes, Viral

KW - Genetic Variation

KW - Herpesvirus 4, Human

KW - Humans

KW - Infectious Mononucleosis

KW - Mice

KW - Mice, Nude

KW - Molecular Sequence Data

KW - Nasopharyngeal Neoplasms

KW - Open Reading Frames

KW - Repetitive Sequences, Nucleic Acid

KW - Selection, Genetic

KW - Sequence Alignment

KW - Tumor Escape

KW - Viral Proteins

KW - Viral Structural Proteins

KW - Journal Article

M3 - Article

VL - 23

SP - 2192

EP - 2201

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 6

ER -