Genotypic analysis of two hypervariable human cytomegalovirus genes.
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.
Bradley
Amanda J
AJ
MRC Virology Unit, Institute of Virology, University of Glasgow, Glasgow, United Kingdom.
Kovács
Ida J
IJ
Gatherer
Derek
D
Dargan
Derrick J
DJ
Alkharsah
Khaled R
KR
Chan
Paul K S
PK
Carman
William F
WF
Dedicoat
Martin
M
Emery
Vincent C
VC
Geddes
Colin C
CC
Gerna
Giuseppe
G
Ben-Ismaeil
Bassam
B
Kaye
Steve
S
McGregor
Alistair
A
Moss
Paul A
PA
Pusztai
Rozalia
R
Rawlinson
William D
WD
Scott
Gillian M
GM
Wilkinson
Gavin W G
GW
Schulz
Thomas F
TF
Davison
Andrew J
AJ
D000349:Africa; D000595:Amino Acid Sequence; D001208:Asia; D001315:Australia; D019743:Chemokines, CXC / Q000235:genetics*; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology; D005060:Europe; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009656:North America; D010802:Phylogeny; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics*
D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; D014764:Viral Proteins; C121017:viral chemokine CXC-1, Cytomegalovirus