Developing Bioinformatics Computer Skills

Chapter 8. Multiple Sequence Alignments, Trees, and Profiles

In Chapter 7, we introduced the idea of using sequence alignment to find and compare pairs of related sequences. Biologically interesting problems, however, often involve comparing more than two sequences at once. For example, a BLAST or FASTA search can yield a large number of sequences that match the query. How do you compare all these resulting sequences with each other? In other words, how can you examine these sequences to understand how they are related to one another?

One approach is to perform pairwise alignments of all pairs of sequences, then study these pairwise alignments individually. It's more efficient (and easier to comprehend), however, if you compare all the sequences at once, then examine the resulting ensemble alignment. This process is known as multiple sequence alignment. Multiple sequence alignments can be used to study groups of related genes or proteins, to infer evolutionary relationships between genes, and to discover patterns that are shared among groups of functionally or structurally related sequences. In this chapter, we introduce some tools for creating and interpreting multiple sequence alignments and describe some of their applications, including phylogenetic inference and motif discovery. Phylogenetic inference and motif discovery are rooted in evolutionary theory, so before we dive into a discussion of that area of bioinformatics, let's take a minute to review the history and theory ...