title: Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. andrew.rambaut@zoo.ox.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Rambaut
mesh_terms: D004279:DNA, Viral / Q000032:analysis; D003716:Dengue Virus / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D016013:Likelihood Functions; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods; D012984:Software; D014759:Viral Envelope Proteins / Q000145:classification / Q000235:genetics
chemical_list: D004279:DNA, Viral; D014759:Viral Envelope Proteins