Well, yes, a content aware solution could mush down to 2 bits per character. I was proposing, though, something more memory efficient than $SEEN{$_}++.
I don't know much about DNA, but googling around a bit, "one DNA sequence per line" could mean 237, 373, etc, characters per line. 373*2= 746, so an MD5 hash could still be significantly smaller.
Also, I don't know if OP's file format has comments or other things besides A/T/G/C.
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