The u-commands are designed to optimize search speed for large datasets. A key technique is using an index on the database that supports rapid retrieval of word counts or seeds. The index can be built in memory on the fly from a FASTA file, or can be pre-built and stored in a UDB file. Using FASTA can be convenient, but with large database load times are longer and more memory is required compared to using a UDB file. The memory required to store a UDB file in memory is approximately the same as the UDB file size. When indexes are created on the fly from a FASTA file, indexing options can be specified on the search command line. This also applies when a centroid database is constructed on the fly during clustering.
The search_local and search_global commands do not use an index. They use a FASTA database file which is loaded into memory without creating an index. The memory required is approximately the same as the FASTA file size. Using these commands saves memory and can be convenient for small datasets, but searches are usually slower.