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Recently, there have been some reports from DNA sequences where they do not show any significant conservation but able to drive same expression pattern. In other words, while these sequences look very divergent, they are functionally very simialar.

Alignment free sequence comparison models aim to compare these sequences based on their functionality. The first alignment- free sequence comparison model proposed in 1986 by Blaisdell and from that time it has recieved a great deal of attention by researchers. However, the overwhelming majority of reports about alignment free models have been published over last 10 years.

One application of these models are predicting and/or detecting cis-regulatory modules.