Estimating the rate of molecular evolution: Incorporating non-contemporaneous sequences into maximum likelihood phylogenies

Abstract

Motivation: TipDate is a program that will use sequences that have been isolated at different dates to estimate their rate of molecular evolution. The program provides a maximum likelihood estimate of the rate and also the associated date of the most recent common ancestor of the sequences, under a model which assumes a constant rate of substitution (molecular clock) but which accommodates the dates of isolation. Confidence intervals for these parameters are also estimated. Results: The approach was applied to a sample of 17 dengue virus serotype 4 sequences, isolated at dates ranging from 1956 to 1994. The rate of substitution for this serotype was estimated to be 7.91 x 10-4 substitutions per site per year (95% confidence intervals of 6.07 x 10-4, 9.86 x 10-4). This is compatible with a date of 1922 (95% confidence intervals of 1900-1936) for the most recent common ancestor of these sequences. Availability: TipDate can be obtained by WWW from {http: //evolve.zoo.ox.ac.uk/software}. The package includes the source code, manual and example files. Both UNIX and Apple Macintosh versions are available from the same site.