For this chapter, as well as Chapters 12 and 13, we turn to the important genomics and bioinformatics problem of identifying biological function based on nucleotide and amino acid sequences.

Assigning function based on sequence similarity

A common problem in molecular biology is that you are faced with a gene or a gene product and you have no clue from experimental studies as to its function. In this context a critical contribution of bioinformatics is to attribute the sequence of a gene or a gene product a function. As one example, a genome sequencing project may give rise to tens of thousands of predicted protein sequences. In such a case we want to assign as many of these as possible a biological function using computational tools. In this manner we avoid many laborious wetlab experiments. In addition to genome sequencing projects, there are other more specialized situations where we want to find functions of genes. For instance, we could identify genes as being related to a specific genetic trait or disease, or a set of genes as being expressed under certain conditions.

A number of computational tools are available to predict a biological function associated with a protein sequence. In this chapter we will see an example in which we assign a function to a protein based on sequence similarity. Consider the human gene encoding the protein BRCA1, originally sequenced in 1994 (Miki et al., 1994). It was found to be related in sequence to a yeast protein RAD9. This yeast protein is involved in cell cycle control. This observation gave scientists a hint about possible roles of the BRCA1 gene. We see here an example of inferring a function based on a homology relationship to a protein that has already been functionally characterized. We will see yet another example of this situation in this chapter, where we will make use of BLAST to identify a homology relationship. We already encountered BLAST in the context of the BCR–ABL fusion protein in Chapter 7.