Aligning DNA sequences to minimize the change in protein

Abstract

We study an alignment model for coding DNA sequences recently proposed by J. Hein that takes into account both DNA and protein information, and attempts to minimize the total amount of evolution at both DNA and protein levels. Assuming that the gap penalty function is affine, we design a quadratic time dynamic programming algorithm for the model. Although the algorithm theoretically solves an open question of Hein, its running time is impractical because of the large constant factor embedded in the quadratic time complexity function. We therefore consider a mild simplification named Context-free Codon Alignment of Hein's model and present a much more efficient algorithm for the simplified model. The algorithms have been implemented and tested on both real and simulated sequences, and it is found that they produce almost identical alignments in most cases. Furthermore, we extend our model and design a heuristic algorithm to handle frame-shift errors and overlapping frames in coding regions.