Inversion breakpoints and the evolution of supergenes

Abstract

The coexistence of discrete morphs that differ in multiple traits is common within natural populations of many taxa. Such morphs are often associated with chromosomal inversions, presumably because the recombination suppressing effects of inversions help maintain alternate adaptive combinations of alleles across the multiple loci affecting these traits. However, inversions can also harbour selected mutations at their breakpoints, leading to their rise in frequency in addition to (or independent from) their role in recombination suppression. In this review, we first describe the different ways that breakpoints can create mutations. We then critically examine the evidence for the breakpoint-mutation and recombination suppression hypotheses for explaining the existence of discrete morphs associated with chromosomal inversions. We find that the evidence that inversions are favoured due to recombination suppression is often indirect. The evidence that breakpoints harbour mutations that are adaptive is also largely indirect, with the characterization of inversion breakpoints at the sequence level being incomplete in most systems. Direct tests of the role of suppressed recombination and breakpoint mutations in inversion evolution are thus needed. Finally, we emphasize how the two hypotheses of recombination suppression and breakpoint mutation can act in conjunction, with implications for understanding the emergence of supergenes and their evolutionary dynamics. We conclude by discussing how breakpoint characterization could improve our understanding of complex, discrete phenotypic forms in nature.

Keywords: chromosomal inversion; genome evolution; linkage; mutation; recombination.

Box 1 – Figure 1. Known molecular mechanisms generating inversions

White and grey arrows represent genes, with their orientation indicated by the direction of the arrows. A. Ectopic recombination between similar elements (transposable elements or duplicated genes) in opposite orientation in a DNA segment leads to the inversion of the interspacing sequence. B. Fours single strand breaks (a, b, c, and d) lead to two staggered breaks. Through end repair and reattachment in the opposite orientation an inversion is generated with sequence duplication at both breakpoints (black and grey genes). The number above the DNA stretch are used here to illustrate the change in orientation of the sequence.

Box 2 – Figure 1. Flagship examples of supergenes

A. Boechera stricta subspecies types. The East subspecies has smaller leaves with more trichomes. Photo credit: Cheng-Ruei Lee. B. Multiple QTLs were detected in the Bs1 inversion. The red, blue dashed and grey-dashed lines correspond to different composite traits obtained through discriminant function analysis. See Lee et al., 2017 for more details. The two black-dashed lines correspond to the position of the inversion breakpoints. Breakpoints are of the cut-and-paste type for the Bs1 inversion. Figure redrawn and modified with the permission of the authors. C. Heliconius numata aposematic morphs, involved in Müllerian mimicry rings with other butterflies. D. Aposematic morphs in H. numata are associated with adjacent inversions (spanning the genomic region indicated by P) on linkage group 15 (LG15), encompassing at least three loci (Yb, Sb and N) associated with mimetic color morphs in H. melpomene.

Figure 1. Hypotheses underlying selective advantages to inversions and scenarios for supergene emergence

A. Hypotheses explaining a selective advantage to inversions. B. Scenarios for supergene emergence. Grey squares represent a chromosome; red dots are adaptive variants affecting a selected trait; black bars are inversion breakpoints.

Figure 2. Possible mechanisms creating mutations at inversion breakpoints

A. An inversion generated through ectopic recombination affects the transcription level of two genes by changing their positions in the genome relative to a promoter. B. An inversion generated through staggered breaks generates a new chimeric gene, while avoiding the loss of the donor genes because of duplication. Grey and black arrows represent genes, with orientation indicated via arrow direction; a, b, c, d represent single strand breaks, resulting in two staggered breaks.

Figure 3. Characterizing breakpoints at the DNA sequence level

A. Using short-read sequencing technologies can lead to misassembly of inversion breakpoints, for example due to duplications generated through staggered breaks (Ranz et al., 2007). Grey and black arrows represent genes, with orientation indicated by the direction of arrows. B. A method to characterize breakpoint sequences using a single reference genome and short read data, as developed by Corbett-Detig and colleagues (Russell B. Corbett-Detig et al., 2012). Black arrows symbolize aligned reads on the reference genome, while grey arrows symbolize their unaligned paired reads. Breakpoint sequence characterization is possible by using the black and grey read pairs to generate de novo assembly of the breakpoint region. Figure redrawn and modified from (Russell B. Corbett-Detig et al., 2012) with the permission of the authors.