Limits of homology detection by pairwise sequence comparison

Motivation: Noise in database searches resulting from random sequence simil arities increases as the databases expand rapidly. The noise problems are n ot a technical shortcoming of the database search programs, but a logical c onsequence of the idea of homology searches. The effect can be observed in simulation experiments. Results: We have investigated noise levels in pairwise alignment based data base searches. The noise levels of 38 releases of the SwissProt database, d isplay perfect logarithmic growth with the total length of the databases. C lustering of real biological sequences reduces noise levels, but the effect is marginal.