Ganciclovir was used to detect null mutations in the tk gene in cell culture (3), giving f = 6.0 ´ 10^-5 (see (2)). Sequencing revealed 45 indels, 17 missense mutations, and 5 nonsense mutations (67 mutations in total). There are T_s = 76 possible nonsense substitutions in this gene, c = 3 approximately (2), L = 1128, and tk null mutations are selectively neutral in cell culture in the absence of the drug (a = 1) (1). Hence, m_s/n/c = 3 ´ 6.0 ´ 10^-5 ´ 5 / 67 / 3 / 76 = 5.9 ´ 10^-8, m_i/n/c = 6.0 ´ 10^-5 ´ 45 / 67 / 3 / 1128 = 1.2 ´ 10^-8, and d = 0.17.

1. Challberg, M. D. and T. J. Kelly. 1989. Animal virus DNA replication. Annu. Rev. Biochem. 58:671-717.

2. Drake, J. W. and C. B. Hwang. 2005. On the mutation rate of herpes simplex virus type 1. Genetics 170:969-970.

3. Lu, Q., Y. T. Hwang, and C. B. Hwang. 2002. Mutation spectra of herpes simplex virus type 1 thymidine kinase mutants. J. Virol. 76:5822-5828.