Fig. 1.

(A) An ancestral mammalian phenotype is encoded by a set of genomic regions (such as CNEs) that are required for that trait. Species or clade-specific trait inactivation events may occur via inactivating mutations in any of the genomic regions related to the trait (a schematic “phenotree” is shown, where a phenotype across species is projected on the phylogenetic tree). As a consequence of trait inactivation, all related genomic regions switch from purifying to neutral selection, resulting in decay of the genomic region over time, and matching evolutionary profiles of the eroding elements and lost trait. Independent loss patterns are in general far less common than single-clade loss patterns, and are expected to match independent CNE inactivation events in the mammalian phylogeny with higher specificity. (B) A proposed “reverse genomics” approach to link human IL-CNEs to a large data set of scored phenotypes by matching the evolutionary patterns for many IL-CNEs (projected onto one-dimensional vectors) against the evolutionary patterns of many mammalian traits.