The non-orthologous gene displacement, or NOD, describes a variant form of a system or pathway in which some expected component is replaced by a functional equivalent that differs in its evolutionary origin. The NOD may be the most familiar example of a bioinfotrope. A non-orthologous gene displacement often is discovered as the explanation for a recurring pathway hole; the term was introduced by Koonin, et al. in 1996 (PMID: 8855656). A characteristic of a pathway variant that includes an NOD is that the pathway itself appears identical when it is described by controlled vocabulary terms for the functions of individual proteins (such as Enzyme Commission EC numbers or Gene Ontology GO terms) rather than by the identities of the families to which component proteins belong. Other possible explanations for a recurring pathway hole include recurring missed gene calls, poor sensitivity of defining protein families, chemically distinct pathways that pass through different chemical intermediates, and shortened pathways that enter at a later step or stop and branch at an earlier step.