Adv. Biophys., Vol. 36, pp. 159-206 (1999) MULTIPLE SEQUENCE ALIGNMENT: ALGO- RITHMS AND APPLICATIONS OSAMU GOTOH Saitama Cancer Center Research Institute, Ina-machi, Saitama 362-0806,Japan A central theme of modern molecular biology is to elucidate the interrelationships among genetic information, higher-order struc- tures of gene products, and their biological functions. Because of the inheritable nature of the genetic information, all of these prop- erties are under the influence of molecular evolution. For short, we call the relationships among function, evolution, sequence, and structure “FESS” relationships. Studies on the FESS relationships are becoming more and more important, yet they are complicated and demanding with ex- plosive accumulation of structural and functional data for genes and proteins of various organisms. Most symbolically, the sizes of DNA and protein sequence databases are exponentially increasing, espe- cially with the steady progress of genome projects. The three-di- mensional (3D) structural databases are also growing rapidly, chas- ing the sequence databases. It is absolutely necessary to develop computational tools for storing and retrieving these massive amounts of data. However, an even more important and challeng- ing research theme is to analyze the data and extract the essence vaguely encoded in the mass of information. Unquestionably, it is of primary importance to decipher genomic DNA or protein amino acid sequences in relation to their 159