Effect of gene location on the evolutionary rate of amino acid substitutions in herpes simplex virus proteins.

In an effort to understand the organization of genes in the herpes simplex virus (HSV-1) genome, I tested the idea that the location of a gene may be related to the evolutionary rate of amino acid sequence variation in the encoded protein. A measure of protein sequence divergence was calculated for homologous proteins in the UL region of six alphaherpesviruses including HSV-1, and this parameter was plotted against position in the HSV-1 genome. The results revealed a cluster of highly conserved proteins (UL27-UL33) encoded near the middle of UL. A similar analysis was restricted to HSV-1 and HSV-2 permitting an examination of U(S) proteins and proteins encoded in repeated regions at the segment ends. This analysis showed that U(S) proteins as a group are more highly divergent than those encoded in UL. A high degree of divergence was also observed in proteins coded at the segment ends including RL1 (gamma(1)34.5), RL2 (alpha0), UL1 (glycoprotein L), UL56, U(S)1, and U(S)12. It is suggested that conserved proteins UL27-UL33 are encoded near the middle of UL to take advantage of a low local mutation rate. Highly divergent proteins are suggested to be encoded selectively in U(S) because of a comparatively rapid evolutionary rate with which genes can be introduced and removed from S in response to environmental variation.