False occurrences of functional motifs in protein sequences highlight evolutionary constraints

Background: False occurrences of functional motifs in protein sequences can be considered as random events due solely to the sequence composition of a proteome. Here we use a numerical approach to investigate the random appearance of functional motifs with the aim of addressing biological questions such as: How are organisms protected from undesirable occurrences of motifs otherwise selected for their functionality? Has the random appearance of functional motifs in protein sequences been affected during evolution? Results: Here we analyse the occurrence of functional motifs in random sequences and compare it to that observed in biological proteomes; the behaviour of random motifs is also studied. Most motifs exhibit a number of false positives significantly similar to the number of times they appear in randomized proteomes (= expected number of false positives). Interestingly, about 3% of the analysed motifs show a different kind of behaviour and appear in biological proteomes less than they do in random sequences. In some of these cases, a mechanism of evolutionary negative selection is apparent; this helps to prevent unwanted functionalities which could interfere with cellular mechanisms. Conclusion: Our thorough statistical and biological analysis showed that there are several mechanisms and evolutionary constraints both of which affect the appearance of functional motifs in protein sequences.