How Selection Acts on Chromosomal Inversions

Abstract

Chromosomal inversions are structural mutations that invert the orientation and thus the sequence of a chromosomal segment; in diploid heterozygous individuals, when one chromosome carries the inverted segment and the other homologous chromosome is noninverted, recombination is strongly or even completely suppressed. Most inversions are deleterious or neutral, but occasionally they are beneficial. Positive selection can establish a new, initially rare inversion via indirect (linked) selection (e.g. when the inversion captures a locally adaptive haplotype and then ‘hitchhikes’ with it) or via direct positive selection (e.g. when a beneficial mutation arises fortuitously at the breakpoints). After their establishment, adaptive inversions often seem to be maintained by balancing selection in a polymorphic state, that is, they are neither lost nor do they become fixed at 100% frequency. Such balancing selection acting on inversion polymorphisms might involve overdominance, associative overdominance, negative frequency‐dependent selection, spatially and/or temporally varying selection.

Key Concepts

  • Chromosomal inversions are structural mutations that reverse the segment of a chromosome.
  • In heterozygous state, inversions suppress recombination between inverted and noninverted (standard arrangement) chromosomes.
  • Most inversions are deleterious or neutral; rarely they are beneficial.
  • Positive selection can establish an initially rare inversion in a population despite drift.
  • If the inversion happens to capture a locally adapted haplotype, it can ‘hitchhike’ with it and increase in frequency; it has an advantage because it protects the haplotype from recombination and maladaptive gene flow.
  • Another possibility is that the inversion breakpoints directly and fortuitously generate an adaptive mutation.
  • Once established, balancing selection can maintain the inversion polymorphism; this might happen due to heterozygote advantage, frequency‐dependent selection, spatially and/or temporally varying selection.

Keywords: chromosomal inversions; polymorphism; selection; adaptation; positive selection; balancing selection; heterozygote advantage; linkage; recombination

Figure 1. Suppression of recombination and gene flux in the context of inversions. (a) Inversions can be either paracentric (i.e. both breaks occur on one chromosomal arm) or pericentric (i.e. breaks occur on two chromosomal arms and inversions span a centromere). In paracentric inversion heterozygotes, homologous chromosomes form a loop during meiosis (b–d). Single cross‐overs (b) result in the formation of four products: standard (STD) and inverted (INV) nonrecombinant gametes, as well as an acentric fragment lacking a centromere and a dicentric bridge harbouring two centromeres. The former is lost and the latter is torn apart during centromere migration to the cell poles, which results in two nonviable recombinant gametes (indicated by black crosses). In the case of pericentric inversions (not shown here, see Wellenreuther and Bernatchez, for details), meiosis also produces four products: viable STD and INV nonrecombinant gametes as for paracentric inversions, and two nonviable recombinant gametes harbouring large deletions or duplications. (b) Modified from Wellenreuther and Bernatchez L . Exchange of genetic material between STD and INV chromosomal arrangements (gene flux) can nevertheless happen via double crossovers (c) and gene conversion events (d), especially away from the breakpoints (see Korunes and Noor, for details). (d) Modified from Korunes and Noor, .
Figure 2. Selective mechanisms leading to the establishment of inversions. (a) An inversion (INV) captures a locally adapted high‐fitness haplotype (STD4) and protects it from recombing with maladaptive low‐fitness haplotypes (STD1–3). In this ‘local adaptation’ scenario, positive selection acts on locally adapted alleles within the inversion and indirectly on the inversion itself. This mechanism is similar to the ‘coadaptation’ scenario; see main text for details. (b) A neutral inversion (INV1) spreads to intermediate frequency by drift before picking up a beneficial mutation by chance (INV2), which causes the inversion to raise to high frequency via hitchhiking. As in the local adaptation model (a), positive selection acts on the beneficial mutation and not on the inversion itself. (c) Gene disruption caused by an inversion can by chance cause beneficial mutations at either one (INV1 or INV2) or both of the breakpoints (INV3). Here, positive selection directly targets the inversion and its breakpoints instead of its allelic content.
Figure 3. Expected patterns of genetic divergence (for example as measured by FST or Dxy) between standard and inverted chromosomal arrangements. Inversion breakpoints positions are depicted with dashed orange lines. (a) Under neutrality, divergence is expected to be low at the centre of the inversion, where gene flux between arrangements is maximal, and high at the breakpoints, where gene flux is strongly reduced. Importantly, this ‘suspension bridge’ pattern might also reflect strong selection at the breakpoints. (b) Under the ‘local adaptation’ and the ‘coadaptation’ models, we expect to see additional peaks of high divergence in the centre of the inversion and away from the breakpoints: these peaks are centred on locally adapted loci that are maintained by selection despite homogenising gene flux. This pattern has been observed for the In(3R)Payne inversion in the fruit fly D. melanogaster (c) (Kapun et al. ) and, to a lesser extent, for the 2La inversion in the mosquito A. gambiae (d) (Cheng et al. ). Source: Kapun et al. , Cheng et al. , Kapun and Flatt .
Figure 4. Two forms of heterozygote advantage that can maintain inversion polymorphisms. (a) Fitness overdominance (OD) occurs when heterozygotes at a given locus (for example locus C) enjoy a greater fitness than both STD and INV homozygotes. This heterozygote advantage might result from a single overdominant mutation, either at the breakpoints or within the inversion body, whereas in more complex scenarios (e.g. the ‘coadaptation’ model), it might arise from ‘cumulative’ effects of two or more overdominant mutations. (b) Associative overdominance (AOD) refers to heterozygotes at a neutral locus that experience an ‘apparent’ heterozygote advantage because the neutral locus is linked to sites under selection. For example, heterozygotes at the neutral locus C appear to have a greater fitness than STD and INV homozygotes because of negative selection against the linked recessive deleterious mutations A1 and B2 at loci A and B, respectively. In inversion heterozygotes, the negative effects of A1 and B2 are ‘balanced’ by the dominant or partially dominant alleles A2 and B1, thus rendering the STD and INV haplotypes ‘complementary’. AOD can also occur when a neutral locus is linked to a single overdominant locus, as shown in (a): heterozygotes at the neutral B locus have greater fitness than homozygotes because the B locus is linked to the overdominant C locus, the latter being under positive selection.
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Further Reading

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Sturtevant AH and Mather K (1938) The interrelations of inversions, heterosis and recombination. American Naturalist 72: 447–452.

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Durmaz, Esra, Kerdaffrec, Envel, Katsianis, Georgios, Kapun, Martin, and Flatt, Thomas(Sep 2020) How Selection Acts on Chromosomal Inversions. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028745]