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The genomes of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) consist of two covalently joined segments, L and S. Each segment comprises an unique sequence flanked by inverted repeats. We have reported previously the DNA sequences of the S segments in these two genomes, and have identified protein-coding regions therein. In HSV-1, the unique sequence of S contains ten entire genes plus the major parts of two more, and each inverted repeat contains one entire gene; in VZV, the unique sequence of S contains two entire genes plus the major parts of two more, and each inverted repeat contains three entire genes. In this report, an examination of polypeptide sequence homology has shown that each VZV gene has an HSV-1 counterpart, but that six of the HSV-1 genes have no VZV homologues. Thus, although these regions of the two genomes differ in gene layout, they are related to a significant degree. The analysis indicates that the inverted repeats are evidently capable of large-scale expansion or contraction during evolution. The differences in gene layout can be understood as resulting from a small number of recombinational events during the descent of HSV-1 and VZV from a common ancestor.

Evolutionary Comparisons of the S Segments in the Genomes of Herpes Simplex Virus Type 1 and Varicella-Zoster Virus