Most human cytomegalovirus (HCMV) genes are highly conserved in sequenceamongstrains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXCchemokine,andUL139,whichis predicted to encode a membrane glycoprotein. The sequen- ces of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North Amer- ica. 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 geno- types, 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 multi- ple genotypes indicated that mixed infections are common. For both genes, the degree of diver- gence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and themodeof evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selectionwasdetected marginally at best. No evidence was found for linkage disequi- librium. The emerging scenario is that the HCMV genotypes developed in early human popula- tions (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times.
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