I. Introduction
As a typical NP-hard combinatorial optimization problem, the traveling salesman problem (TSP) has been widely studied and achieved remarkable results [1]–[3]. Many variants of the classic TSP have also been investigated. The quadratic traveling salesman problem (QTSP) is one of them. It is inspired by the problem of finding the optimal Permuted Markov (PM) model [4] and the optimal Permuted Variable Length Markov (PVLM) model [5] for a given set of DNA sequences. This problem is important in bioinformatics and genome research for the recognition of transcription factor binding sites and splice sites.