In absence of significant sequence similarity, remote homology between proteins can be confused with analogy and in such a case, shared ancestry can be inferred in light of certain unique and common features. In the present study, to understand the evolutionary origin of catalytic domain of large subunit of ring-hydroxylating oxygenases (RHOs), belonging to the Bet v1-like superfamily, structure-based phylogenies have been derived from structural alignment of representative proteins of the superfamily. A careful inspection of the structural relatedness of RHOs with the rest of the families showed closest similarity between RHO catalytic domain and PA1206-like protein. In addition, phylogenetic relationship of the Rieske domain of the large subunit of RHOs with functionally and structurally similar proteins has also been elucidated so as to postulate the most possible events leading to the genesis of the large subunit of RHOs.