Abstract
Chromosome inversions are important contributors to standing genetic variation in Drosophila subobscura. Presently, the species is experiencing a rapid replacement of high-latitude by low-latitude inversions associated with global warming. Yet not all low-latitude inversions are correlated with the ongoing warming trend. This is particularly unexpected in the case of O7 because it shows a regular seasonal cycle that peaks in summer and rose with a heatwave. The inconsistent behavior of O7 across components of the ambient temperature suggests that is causally more complex than simply due to temperature alone. In order to understand the dynamics of O7, high-quality genomic data are needed to determine both the breakpoints and the genetic content. To fill this gap, here we generated a PacBio long read-based chromosome-scale genome assembly, from a highly homozygous line made isogenic for an O3+4+7 chromosome. Then we isolated the complete continuous sequence of O7 by conserved synteny analysis with the available reference genome. Main findings include the following: (i) the assembled O7 inversion stretches 9.936 Mb, containing > 1,000 annotated genes; (ii) O7 had a complex origin, involving multiple breaks associated with non-B DNA-forming motifs, formation of a microinversion, and ectopic repair in trans with the two homologous chromosomes; (iii) the O7 breakpoints carry a pre-inversion record of fragility, including a sequence insertion, and transposition with later inverted duplication of an Attacin immunity gene; and (iv) the O7 inversion relocated the major insulin signaling forkhead box subgroup O (foxo) gene in tight linkage with its antagonistic regulatory partner serine/threonine–protein kinase B (Akt1) and disrupted concerted evolution of the two inverted Attacin duplicates, reattaching them to dFOXO metabolic enhancers. Our findings suggest that O7 exerts antagonistic pleiotropic effects on reproduction and immunity, setting a framework to understand its relationship with climate change. Furthermore, they are relevant for fragility in genome rearrangement evolution and for current views on the contribution of breakage versus repair in shaping inversion-breakpoint junctions.
Highlights
Chromosome inversions are arguably the genetic traits with the earliest and richest record of associations with climate (Hoffmann and Rieseberg, 2008)
non-homologous end joining (NHEJ) inversions without duplications at their ends would originate via cut-and-paste (Wesley and Eanes, 1994), whereas those with inverted duplications at their ends would originate via staggered breaks in one or the two breakpoints
Two staggering models for the origin of the inverted duplications have been proposed (Kehrer-Sawatzki et al, 2005; Matzkin et al, 2005; Ranz et al, 2007): according to the isochromatid model, the duplications would be the filled-in single-stranded overhangs that would result from paired single strand breaks (SSBs) located staggered with each other on opposite strands of the same chromatid (Kehrer-Sawatzki et al, 2005), whereas according to the chromatid model, the duplications would result from unequal exchange between paired sister chromatids, each with one of two paired staggered double-strand breaks (DSBs) at each breakpoint (Matzkin et al, 2005)
Summary
Chromosome inversions are arguably the genetic traits with the earliest and richest record of associations with climate (Hoffmann and Rieseberg, 2008). The second mechanism is chromosomal breakage and ectopic repair via non-homologous end joining (NHEJ) This mechanism either does not generate duplications or generates them but at the ends of the inverted state only. The NEHJ mechanism rests upon the occurrence of two or more DSBs. But the source of the DSBs (whether environmental, such as ionizing radiation, or spontaneous, such as non-B DNA-associated sequence instability, where non-B DNA denotes any DNA conformation that is not in the canonical right-handed B form; Lobachev et al, 2007; Zhao et al, 2010; Farré et al, 2015), the relative contributions of breakage versus repair to shaping breakpoint junctions (Ranz et al, 2007; Kramara et al, 2018; Scully et al, 2019), and the relative frequency with which the joined broken ends are from the same chromatid (isochromatid model) versus two distinct sisters (chromatid model) (Ranz et al, 2007) or even, as has been more recently suggested by Orengo et al (2019), non-sister chromatids (chromosome model) are additional open questions
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