A fluctuation test was performed by growing a total of 227 cultures, each inoculated with 200 pfu, and testing them for the presence of anti-haemagglutinin monoclonal antibody resistance mutants (2).  Mutation rates were estimated using the null-class method.  Cultures were divided in three experimental blocks, yielding m = 1.4 ´ 10^-4 s/r, m = 6.0 ´ 10^-5 s/r and m = 1.7 ´ 10^-4 s/r (geometric mean: 1.1 ´ 10^-4 s/r).  Four different nucleotide substitutions were identified after sequencing 5 clones.  Given the low number of clones sequenced, it is likely that T_s > 4.  Drake and Holland (1) argued that the most likely value is T_s = 7.5, assuming that the distribution of mutation counts across sites is Poisson.  However, if some mutations are more likely than others, this assumption may not be satisfied.  Independent evidence comes from the author’s (2) quote of a previous work, in which three additional resistance mutations were found, yielding T_s = 7 in total.  Hence, it seems that the value T_s = 7.5 given by Drake and Holland is robust.  According to this, m_s/n/r = 3 ´ 1.1 ´ 10^-4 / 7.5 = 4.4 ´ 10^-5.

 

 

    1.    Drake, J. W. and J. J. Holland. 1999. Mutation rates among RNA viruses. Proc. Natl. Acad. Sci. USA 96:13910-13913.

    2.    Schrag, S. J., P. A. Rota, and W. J. Bellini. 1999. Spontaneous mutation rate of measles virus: direct estimation based on mutations conferring monoclonal antibody resistance. J Virol. 73:51-54.