Gene evolution and drug discovery

Mutation and selection are the principle forces governing gene and protein sequence. Mutation is the major source of variation, and selection removes variation. Although many mutations are likely to be neutral with respect to natural selection, much of the extant sequence that is functionally important has experienced selective pressures in the past. By examining the history of DNA sequences, we can infer the functional importance of particular residues and the selective pressures that have influenced their evolution. In this chapter, we review the most interesting approaches for inferring the evolutionary history of DNA and protein sequences and indicate how these analyses can be useful in the drug discovery process.