Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Genotypic analysis of two hypervariable human cytomegalovirus genes
AU - Bradley, Amanda J.
AU - Kovács, Ida J.
AU - Gatherer, Derek
AU - Dargan, Derrick J.
AU - Alkharsah, Khaled R.
AU - Chan, Paul K. S.
AU - Carman, William F.
AU - Dedicoat, Martin
AU - Emery, Vincent C.
AU - Geddes, Colin C.
AU - Gerna, Giuseppe
AU - Ben-Ismaeil, Bassam
AU - Kaye, Steve
AU - McGregor, Alistair
AU - Moss, Paul A.
AU - Pusztai, Rozalia
AU - Rawlinson, William D.
AU - Scott, Gillian M.
AU - Wilkinson, Gavin W. G.
AU - Schulz, Thomas F.
AU - Davison, Andrew J.
PY - 2008/9
Y1 - 2008/9
N2 - Most human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139, which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times.
AB - Most human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139, which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times.
KW - Africa
KW - Amino Acid Sequence
KW - Asia
KW - Australia
KW - Chemokines, CXC
KW - Cytomegalovirus
KW - Cytomegalovirus Infections
KW - Europe
KW - Evolution, Molecular
KW - Genotype
KW - Humans
KW - Membrane Glycoproteins
KW - Molecular Sequence Data
KW - North America
KW - Phylogeny
KW - Polymorphism, Genetic
KW - Sequence Alignment
KW - Sequence Analysis, DNA
KW - Viral Proteins
U2 - 10.1002/jmv.21241
DO - 10.1002/jmv.21241
M3 - Journal article
C2 - 18649324
VL - 80
SP - 1615
EP - 1623
JO - Journal of Medical Virology
JF - Journal of Medical Virology
SN - 0146-6615
IS - 9
ER -