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We present a new probabilistic model of sequence evolution, allowing indels of arbitrary length, and give sequence alignment algorithms for our model. Previously implemented evolutionary models have allowed (at most) single-residue indels or have introduced artifacts such as the existence of indivisible "fragments." We compare our algorithm to these previous methods by applying it to the structural homology dataset HOMSTRAD, evaluating the accuracy of (1) alignments and (2) evolutionary time estimates. With our method, it is possible (for the first time) to integrate probabilistic sequence alignment, with reliability indicators and arbitrary gap penalties, in the same framework as phylogenetic reconstruction. Our alignment algorithm requires that we evaluate the likelihood of any specific path of mutation events in a continuous-time Markov model, with the event times integrated out. To this effect, we introduce a "trajectory likelihood" algorithm (Appendix A). We anticipate that this algorithm will be useful in more general contexts, such as Markov Chain Monte Carlo simulations.

Original publication

DOI

10.1093/molbev/msh043

Type

Journal article

Journal

Mol Biol Evol

Publication Date

03/2004

Volume

21

Pages

529 - 540

Keywords

Algorithms, Evolution, Molecular, Likelihood Functions, Markov Chains, Sequence Alignment