A supergene is a chromosomal region encompassing multiple neighboring genes that are inherited together because of close genetic linkage, i.e. much less recombination than would normally be expected. This mode of inheritance can be due to genomic rearrangements between supergene variants.

A supergene region can contain few, functionally related genes that clearly contribute to a shared phenotype.

Supergenes have cis-effects due to multiple loci (which may be within a gene, or within a single gene's regulatory region), and tight linkage. They are classically polymorphic, whereby different supergene variants code for different phenotypes.

Classic supergenes include many sex chromosomes, the Primula heterostyly locus, which controls "pin" and "thrum" types, and the locus controlling Batesian mimetic polymorphism in Papilio memnon butterflies. Recently discovered supergenes are responsible for complex phenotypes including color-morphs in the white-throated sparrow.

Primula supergene. Pin and thrum morphs of Primula have effects on genetic compatibility (pin style x thrum pollen, or thrum style x pin pollen matings are successful, while pin x pin, and thrum x thrum matings are rarely successful due to pollen-style incompatibility), and have different style length, anther height in the corolla tube, pollen size, and papilla size on the stigma. Each of these effects is controlled by a different locus in the same supergene, but recombinants are occasionally found with traits combining those of "pin" and "thrum" morphs.

The earliest use of the term "supergene" may be in an article by A. Ernst (1936) in the journal Archiv der Julius Klaus-Stiftung für Vererbungsforschung, Sozialanthropologie und Rassenhygiene.

Classically, supergenes were hypothesized to have evolved from less tightly-linked genes coming together via chromosomal rearrangement or reduced crossing over, due to selection for particular multilocus phenotypes. For instance, in Batesian mimicry supergenes in species such as Papilio memnon, genes are required to affect hind-wing, fore-wing, and body colour, and also the presence or absence of long projections (the "tails" of swallowtail butterflies).

The case for the accumulative origin for supergenes was originally based on the work of Nabours on polymorphism for colour and pattern in grouse locusts (Tetrigidae). In Acridium arenosum the colour-patterns are controlled by thirteen genes on the same chromosome, which reassort (recombine) fairly easily. They also occur in Apotettix eurycephalus where they form two tightly linked groups, between which there is 7% crossing-over. Furthermore, in Paratettix texanus there appears to be complete suppression of crossing-over among 24 out of 25 of the colour-pattern genes, which can be distinguished by comparing their effects with those found in other species. Analysis of Nabour's data by Darlington & Mather concluded that the genes responsible for the morphs of Paratettix texanus have been gradually aggregated into a group which acts as a single switch-mechanism. This explanation was accepted by E.B. Ford and incorporated into his accounts of ecological genetics.