Multiple alignment of complete sequences (MACS) in the post-genomic era

Multiple alignment, since its introduction in the early seventies, has beco me a cornerstone of modem molecular biology. It has traditionally been used to deduce structure / function by homology, to detect conserved motifs and in phylogenetic studies. There has recently been some renewed interest in the development of multiple alignment techniques, with current opinion movi ng away from a single all-encompassing algorithm to iterative and / or co-o perative strategies. The exploitation of multiple alignments in genome anno tation projects represents a qualitative leap in the functional analysis pr ocess, opening the way to the study of the co-evolution of validated sets o f proteins and to reliable phylogenomic analysis. However, the alignment of the highly complex proteins detected by today's advanced database search m ethods is a daunting task, In addition, with the explosion of the sequence databases and with the establishment of numerous specialized biological dat abases, multiple alignment programs must evolve if they are to successfully rise to the new challenges of the post-genomic era. The way forward is cle arly an integrated system bringing together sequence data, know-ledge-based systems and prediction methods with their inherent unreliability. The inco rporation of such heterogeneous, often non-consistent, data will require ma jor changes to the fundamental alignment algorithms used to date. Such an i ntegrated multiple alignment system will provide an ideal workbench for the validation, propagation and presentation of this information in a format t hat is concise, clear and intuitive. (C) 2001 Elsevier Science B.V. All rig hts reserved.