Other confounding factors such as differences in evolutionary rates at different sites or among different species also generally do not affect the interpretation of a CSI. By determining the presence or absence of CSIs in an out-group species, one can infer whether the ancestral form of the CSI was an insert or deletion and this can be used to develop a rooted phylogenetic relationship among organisms.

CSIs are discovered by looking for shared changes in a phylogenetic tree constructed from protein