title: Estimating evolutionary rates using time-structured data: a general comparison of phylogenetic methods.
abstract: In rapidly evolving pathogens, including viruses and some bacteria, genetic change can accumulate over short time-frames. Accordingly, their sampling times can be used to calibrate molecular clocks, allowing estimation of evolutionary rates. Methods for estimating rates from time-structured data vary in how they treat phylogenetic uncertainty and rate variation among lineages. We compiled 81 virus data sets and estimated nucleotide substitution rates using root-to-tip regression, least-squares dating and Bayesian inference.
  
  
  
  Although estimates from these three methods were often congruent, this largely relied on the choice of clock model. In particular, relaxed-clock models tended to produce higher rate estimates than methods that assume constant rates. Discrepancies in rate estimates were also associated with high among-lineage rate variation, and phylogenetic and temporal clustering. These results provide insights into the factors that affect the reliability of rate estimates from time-structured sequence data, emphasizing the importance of clock-model testing.
  
  
  
  sduchene@unimelb.edu.au or garzonsebastian@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online.
authors.affiliation: Marie Bashir Institute of Infectious Diseases and Biosecurity, Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.|School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.|Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Duchêne
authors.affiliation: Marie Bashir Institute of Infectious Diseases and Biosecurity, Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.|School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Jemma L
authors.initials: JL
authors.lastname: Geoghegan
authors.affiliation: Marie Bashir Institute of Infectious Diseases and Biosecurity, Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.|School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Simon Y W
authors.initials: SY
authors.lastname: Ho
mesh_terms: D001419:Bacteria / Q000235:genetics; D001499:Bayes Theorem; D008957:Models, Genetic; D010802:Phylogeny; D015203:Reproducibility of Results; D014780:Viruses / Q000235:genetics