A new look at tree models for multiple sequence alignment

Abstract

Evolutionary trees are frequently used as the underlying model in the design of algorithms, optimization criteria and software packages for multiple sequence alignment (MSA). In this paper , we reexamine the suitability of trees as a universal model for MSA in light of the broad range of biological questions that MSA's are used to address. A tree model consists of a tree topology and a model of accepted mutations along the branches. After surveying the major applications of MSA, examples from the molecular biology literature are used to illustrate situations in which this tree model fails. This occurs when the relationship between residues in a column cannot be described by a tree; for example, in some structural and functional applications of MSA. It also occurs in situations, such as lateral gene transfer, where an entire gene cannot be modeled by a unique tree. In cases of nonparsimonous data or convergent evolution, it may be diicult to nd a consistent mutational model. We hope that this survey will promote dialogue between biologists and computer scientists, leading to more biologically realistic research on MSA.