Like many undergraduate students, I learned about the linear, universal molecular clock: the homogeneous rate of nucleotide change over time. When I sat down to actually do analyses of molecular data, I was confounded by the array of options to treat DNA sequences with a molecular clock. Relaxed clock? Strict clock? Local clock? I had no idea what was going on.
With the growing amount of sequence data, the performance of molecular-clock analyses will increasingly rely on rigorous model selection and the identification of accurate, informative calibrations.
Ho and Duchêne have recently provided a nice, practical review for choosing methods to apply molecular clocks to sequence data. Even though some molecular clock parameters are reduced to a single check box in some buried software menu, the consequences of not considering your options can lead to significant error in the estimation of evolutionary timescales. Using this review, you should be able to make an informed choice based on your taxa, question, data set, and evolutionary time frame.
Ho S.Y.W. & Duchêne S. (2014). Molecular-clock methods for estimating evolutionary rates and timescales, Molecular Ecology, 23 (24) 5947-5965. DOI: http://dx.doi.org/10.1111/mec.12953