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It's not easy to tell in the absence of test data how big this hash is
+, 
or how many time these loops iterate, but given the sizes of the data 
+files 
mentioned in the OP, and the timing information you've supplied above,
+ it 
appears that they may be substantial.

The next thing I looked at was the section of code where you 'band pas
+s' filter 
the matches into a temporary array.

Finally (for now), you use this construct:
%{ $sets{ $fasta_id }[ $setscounter ] } = ();
To empty arrays in several places. Whilst there is nothing wrong with 
+this, I think
 it is clearer, and may be slightly quicker to use
 undef $sets{ $fasta_id }[ $setscounter ] };