Sebastián Duchêne1,2,3, Jemma L Geoghegan1,2, Edward C Holmes1,2, Simon Y W Ho2. 1. Marie Bashir Institute of Infectious Diseases and Biosecurity, Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. 2. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia. 3. Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract
MOTIVATION: 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. RESULTS: 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. CONTACT: sduchene@unimelb.edu.au or garzonsebastian@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online.
MOTIVATION: 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. RESULTS: 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. CONTACT: sduchene@unimelb.edu.au or garzonsebastian@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online.
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