Genetic architecture and balancing selection: the life and death of differentiated variants

Abstract

Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems.

Supergene evolution triggered by the introgression of a chromosomal inversion

“…Our results show that, as previously hypothesised 1,6,13 , complex balanced polymorphism such as those controlled by supergene may evolve via the differentiation of rearranged haplotypes in separate lineages, followed by adaptive introgression in a host population where differentiated haplotypes are preserved through suppression of recombination, and .…”

“…Supergene alleles are long-range haplotypes with numerous mutations underlying distinct adaptive strategies, often maintained in linkage disequilibrium through the suppression of recombination by chromosomal rearrangements [2][3][4][5] . However, the mechanism governing the formation of supergenes is not well understood, and poses the paradox of establishing divergent functional haplotypes in face of recombination 1,6 . Here, we show that the formation of the supergene alleles encoding mimicry polymorphism in the butterfly Heliconius numata is associated with the introgression of a divergent, inverted chromosomal segment.…”

“…In most documented cases, the maintenance of character associations is mediated by polymorphic rearrangements, such as inversions, which suppress local recombination and allow the differentiated supergene alleles to persist 2,4,5,10,13 . However, the build-up of differentiated haplotypes from initially recombining loci is poorly understood 1,6 . Recombination is necessary to bring into linkage mutations that arise on different haplotypes, but also acts to break down co-adapted combinations.…”

Extremely Divergent Haplotypes in Two Toxin Gene Complexes Encode Alternative Venom Types within Rattlesnake Species

“…The simplest rationale for the persistence of alternative venom types and PLA2 and MP haplotypes within species would appear to be selection for the ability to subdue alternate prey. If so, this would also constitute a mode of balancing selection to maintain venom polymorphism and a very rare instance of balancing selection acting on multiple loci at each of two unlinked gene complexes [1, 53]. …”

“…Even very closely related species—such as the Galapagos finches, East African cichlid fish, or Caribbean Anolis lizards—have evolved distinct species-specific characters for acquiring food or mates. However, in some cases, two or more functionally differentiated variants of particular traits may co-occur at significant frequencies within species [1]. Well-studied examples of such polymorphisms include wing coloration in Heliconius butterflies [2, 3], body coloration in side-blotched lizards [4], and horn size in Soay sheep [5].…”