Asupergene is achromosomal region encompassing multiple neighboringgenes that are inherited together because of closegenetic linkage, i.e. much less recombination than would normally be expected.[1] 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.[2]
Supergenes havecis-effects due to multipleloci (which may be within a gene, or within a single gene'sregulatory region), and tight linkage. They are classicallypolymorphic, whereby different supergene variants code for different phenotypes.
Classic supergenes include manysex chromosomes, thePrimulaheterostyly locus, which controls "pin" and "thrum" types, and the locus controllingBatesian mimetic polymorphism inPapilio memnon butterflies. Recently discovered supergenes are responsible for complex phenotypes including color-morphs in thewhite-throated sparrow.[3][4][5]
Primula supergene. Pin and thrum morphs of Primula have effects on genetic compatibility (pinstyle x thrumpollen, or thrum style x pin pollen matings are successful, while pin x pin, and thrum x thrum matings are rarely successful due to pollen-styleincompatibility), and have different style length,anther height in thecorolla tube, pollen size, andpapilla size on thestigma. 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.[6]
Classically, supergenes were hypothesized to have evolved from less tightly-linked genes coming together viachromosomal rearrangement or reducedcrossing over, due to selection for particular multilocusphenotypes. For instance, in Batesian mimicry supergenes in species such asPapilio 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 onpolymorphism for colour and pattern in grouse locusts (Tetrigidae). InAcridium arenosum the colour-patterns are controlled by thirteen genes on the same chromosome, which reassort (recombine) fairly easily. They also occur inApotettix eurycephalus where they form two tightly linked groups, between which there is 7% crossing-over. Furthermore, inParatettix 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 byDarlington &Mather concluded that the genes responsible for the morphs ofParatettix texanus have been gradually aggregated into a group which acts as a single switch-mechanism.[7][8][9] This explanation was accepted byE.B. Ford and incorporated into his accounts of ecological genetics.[10][11]
This process might involve suppression of crossing-over,translocation of chromosome fragments and possibly occasionalcistron duplication. That crossing-over can be suppressed by selection has been known for many years; Detlefsen and Roberts were able to reduce recombination between the loci for white eyes (w) and miniature wings (m) inDrosophila melanogaster from the normal 36% to 6% in one line and 0.6% in another.[12][13]
Debate has tended to centre round the question, could the component genes in a super-gene have started off on separate chromosomes, with subsequent reorganization, or is it necessary for them to start on the same chromosome? Many scientists today believe the latter, because somelinkage disequilibrium is initially needed to select for tighter linkage, and linkage disequilibrium requires both the previous existence of polymorphisms via some other process, like natural selection, favouring gene combinations.[14] If genes are weakly linked, it is probable that the rarer advantageoushaplotype dies out, leading to the loss of polymorphism at the other locus.
Most people, followingJ.R.G. Turner, therefore argue that supergenes arosein situ due to selection for correlated and epistatic traits, which just happened to have been possible to select via the existence of suitable loci closely linked to the original variant.[15] Turner calls this a "sieve" explanation, and the Turner explanation might be called the "Turner sieve" hypothesis.[16]Maynard Smith agreed with this view in his authoritative textbook.[17] Nevertheless, the question is not definitively settled. The problem is connected to an even larger question, the evolution ofevolvability.
Genomic rearrangements such as inversions can suppress recombination.
Suppressed recombination leads to accumulation of repetitive elements (including to degenerative expansion) in early supergene evolution [Ref Papaya, Fire ant], and to changes in gene expression [ref Fire ant, anther smut].
Gene complexes, in contrast, are simply tightly linked groups of genes, often created viagene duplication (sometimes calledtandem duplication if the duplicates remain side-by-side). Here, each gene has similar though slightly diverged function. For example, the humanmajor histocompatibility complex (MHC) region is a complex of tightly linked genes all acting in the immune system, but has no claim to be a supergene, even though the component genes very likely have epistatic effects and are in strong disequilibrium due in part to selection.
Berdan EL, Flatt T, KozakGM, Lotterhos KE, Wielstra B. 2022 Genomicarchitecture of supergenes: connecting formand function. Phil. Trans. R. Soc. B 377:20210192