Multiple alignments and phylogenetic tree constructions are established techniques for examining the evolutionary history of protease sequences in organisms such as humans, mice, fruitflies, nematode worms and yeast. They also facilitate the mapping of those conserved positions that are important for structure and catalytic function. However, the continued increase in completed or draft genomes offers new opportunities for examining protease evolution across a broader (e.g. more mammals) and deeper (e.g. more invertebrates) phylogenetic range. In addition, the improving annotation not only of proteases, but also of their substrates, interaction partners in proteolytic complexes and endogenous inhibitor proteins now means that aspects of co-evolution can be addressed. The increasing phylogenetic coverage is also important for resolving orthology issues that arise from protease gene duplication or loss in different lineages. Selected sequences will be used to exemplify the utility of Internet resources and present results for these types of analysis.

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