Fine-Scale Position Effects Shape the Distribution of Inversion Breakpoints in Drosophila melanogaster

Abstract

Chromosomal inversions are among the primary drivers of genome structure evolution in a wide range of natural populations. While there is an impressive array of theory and empirical analyses that have identified conditions under which inversions can be positively selected, comparatively little data is available on the fitness impacts of these genome structural rearrangements themselves. Because inversion breakpoints can disrupt functional elements and alter chromatin domains, the precise positioning of an inversion’s breakpoints can strongly affect its fitness. Here, we compared the fine-scale distribution of low frequency inversion breakpoints with those of high frequency inversions and inversions that have gone to fixation between Drosophila species. We identified a number of differences among frequency classes that may influence inversion fitness. In particular, breakpoints that are proximal to insulator elements, generate large tandem duplications, and minimize impacts on gene coding spans are more prevalent in high frequency and fixed inversions than in rare inversions. The data suggest that natural selection acts to preserve both genes and larger cis-regulatory networks in the occurrence and spread of rearrangements. These factors may act to limit the availability of high fitness arrangements when suppressed recombination is favorable.

A chromosome-scale genome assembly and karyotype of the ctenophore Hormiphora californensis

“…The Hi-C matrix from individual Hc3 does not have off-diagonal hotspots ( Figure 2C ), suggesting that both haplotypes of Hc3 chromosome 1 match the genome assembly sequence. Large heterozygous inversions can prevent recombination over large chromosomal regions ( Kirkpatrick 2010 ; McBroome et al 2020 ), therefore these two haplotypes of H. californensis chromosome 1 may be segregating independently. Large heterozygous inversions between the haplotypes in one individual are not prevalent in vertebrate species, but have been observed before in the genomes of other invertebrates, such as in the mosquito Anopheles gambiae ( Corbett-Detig et al 2019 ).…”

Molecular characterization of inversion breakpoints in theDrosophila nasutaspecies group

“…This resembles findings in great apes, where a high rate of homoplasy of inversions was observed (Porubsky et al 2020). Reuse of inversion breakpoints might be due to mutational bias if these regions are particularly prone to breakage, or driven by selection if a specific breakpoint position affects the intrinsic fitness of a new arrangement (McBroome et al 2020). Mutations caused by inversion breakpoints may have diverse consequences, from gene disruptions to generation of new gene duplicates or transfer of regulatory sequences from one gene to another.…”

The Cyclically Seasonal Drosophila subobscura Inversion O7 Originated From Fragile Genomic Sites and Relocated Immunity and Metabolic Genes

“…The O 7 mutation could have altered Akt1 and/or foxo function via multiple non-mutually exclusive mechanisms, such as mutual regulatory interference, considering that they are antagonistic effectors; relocation to the sides of an immunity gene (i.e., AttA2b) expected to be under intense purifying selection on expression (see below); and alteration of the genes' functional neighborhood at higher-order levels of chromatin organization (Farré et al, 2015;McBroome et al, 2020). It could be argued that the nuclear environment of the genes remained basically unaltered, if the reason why they became involved in the rearrangement was that they already were in close spatial proximity to each other in the nucleus.…”

“…Inversions can have direct or/and indirect functional effects (Kirkpatrick, 2010). Direct effects are those ascribable to the mutation per se, as it altered the structure or expression of functional sequences at the breakpoints, or the functional neighborhood of genes in the cell nucleus (McBroome et al, 2020). Indirect effects emanate from their associated recombination-suppression effects when in heterozygous condition, whereby they can bind together into close linkage association particular combinations of alleles at genetically distant loci.…”