High G+C Content of Herpes Simplex Virus DNA: Proposed Role in Protection Against Retrotransposon Insertion

The herpes simplex virus dsDNA genome is distinguished by an unusually high G+C nucleotide content. HSV-1 and HSV-2, for instance, have GC contents of 68% and 70% respectively, while that of the host (human) genome is 41%. To determine how GC content varies with genome location, GC content was measured separately in coding and intergenic regions of HSV-1 DNA. The results showed that the 75 genes constitute a uniform population with a mean GC content of 66.9 ± 4.1%. In contrast, intergenic regions were found in two non-overlapping populations, one with a mean GC content (69.3 ± 4.6% n=32) similar to the coding regions and another where the GC content is lower (56.0 ± 4.9 n=30). Compared to other regions of the genome, intergenic regions with reduced GC content were found to be enriched in local GC minima, CACACA sequences and a primary target sequence (TTAAAA) for retrotransposition events. The results are interpreted to suggest that a high GC content is part of the way HSV-1 protects its genes from invasion by mobile genetic elements active during cell differentiation in the nervous system.