How Selection Acts on Chromosomal Inversions Esra Durmaz ⋆ , Department of Biology, University of Fribourg, Fribourg, Switzerland Envel Kerdaffrec ⋆ , Department of Biology, University of Fribourg, Fribourg, Switzerland Georgios Katsianis, Department of Biology, University of Fribourg, Fribourg, Switzerland Martin Kapun, Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland and Lab of Genome Dynamics, Department of Cell and Developmental Biology, Medical University of Vienna, Vienna, Austria Thomas Flatt, Department of Biology, University of Fribourg, Fribourg, Switzerland ⋆ These authors contributed equally to this work. Advanced article Article Contents • Introduction • How Newly Arisen Inversions Spread by Positive Selection • How Inversion Polymorphisms Are Maintained by Balancing Selection • Conclusions • Acknowledgements Published online: 30 th September 2020 Chromosomal inversions are structural mutations that invert the orientation and thus the sequence of a chromosomal segment; in diploid heterozy- gous 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 occa- sionally 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 bal- ancing 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 over- dominance, associative overdominance, negative frequency-dependent selection, spatially and/or temporally varying selection. eLS subject area: Evolution & Diversity of Life How to cite: Durmaz, Esra; Kerdaffrec, Envel; Katsianis, Georgios; Kapun, Martin; and Flatt, Thomas. How Selection Acts on Chromosomal Inversions, eLS, Vol 1: 307–315, 2020. DOI: 10.1002/9780470015902.a0028745 Introduction Chromosomal inversions are rare, structural mutations that reverse the orientation and thus the gene order of a chromosomal segment, frst discovered in 1919 by Sturtevant in the vinegar fy Drosophila melanogaster (Sturtevant, 1919). Inversions can be small (<1 kb) or large (>1 Mb) and include or exclude the centromere (peri- vs. paracentric inversions) (Figure 1a) (Kirkpatrick, 2010). In contrast to homozygous individuals that either carry two noninverted chromosomes (so-called ‘stan- dard’ homokaryotypes) or two inverted chromosomes (inverted homokaryotypes), inversion heterozygotes (so-called heterokary- otypes) have major problems with proper pairing of chromatids during meiosis, thus causing a strongly reduced frequency of crossing-over and recombination (Figure 1b–d) (Kirkpatrick, 2010). The major genetic property of inversions is, therefore, that they effectively suppress or at least strongly reduce ‘gene fux’, that is, the genetic exchange between homologous chromosomes when in heterozygous state. This can have major consequences for evolutionary processes, as we shall see below. See also: Genomic Rearrangements: Mutational Mechanisms Like other mutations (e.g. single nucleotide changes), a large fraction of newly arisen inversions is expected to be deleterious, for example when they generate structural problems with meio- sis, when their breakpoints disrupt functionally important genes and/or when they negatively impact gene expression, as is the case for several genetic diseases in humans (Castermans et al., 2007; Feuk, 2010; Kirkpatrick 2010; Puig et al., 2015). Purifying (negative) selection will thus act to eliminate such deleterious inversions from the population. In some cases, however, under- dominant inversions with deleterious effects can become fxed by random genetic drift, for instance when the effective popu- lation size is low for a long time and/or when selection against heterokaryotypes is suffciently weak (Lande, 1984; Kirkpatrick and Barton, 2006; Kirkpatrick, 2010). Another large fraction of Volume 1, Issue 2, September 2020 eLS © 2020, John Wiley & Sons, Ltd. www.els.net 307