Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster

Abstract

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. "Sensitive sites" have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions.KEYWORDS chromosomal inversions; Drosophila melanogaster; sensitive sites; structural variation; breakpoints S UCCESSFUL chromosomal inversions are generally thought to be favorable due to reduced recombination rates between arrangements (Krimbas and Powell 1992;Hoffmann and Rieseberg 2008;Kirkpatrick 2010). In the majority of theoretical treatments, it is believed that inversions are favored because they suppress recombination between genetically distant alleles that are favored in similar contexts. For example, this can result from an array of biological processes including local adaptation (Kirkpatrick and Barton 2006), sex chromosome evolution (Charlesworth et al. 2005), and maintenance of segregation distortion complexes (Lyon 2003). Consistent with this idea, longer chromosomal inversions are expected to be favored by selection relative to shorter inversions because they can suppress recombination between a larger number of genetically distant loci (Crumpacker and Kastritsis 1967;Krimbas and Powell 1992). Indeed, numerous studies in Drosophila have shown that high frequency and fixed inversions are significantly longer than rare and low frequency inversions (Olvera et al. 1979;Ruiz et al. 1984;Cáceres et al. 1997). Furthermore, common inversions are significantly longer than theoretical predictions of the length distribution that should be generated through neutral processes (Van Valen and Levins 1968;Brehm and Krimbas 1991;Krimbas and Powell 1992). Although some evidence indicates that intermediate length inversions are fa...

Genomics of natural populations: Evolutionary forces that establish and maintain gene arrangements in Drosophila pseudoobscura

“…Other possible mechanisms for inversions to directly generate variation in the population include setting up conditions for meiotic drive (Novitski, ) and disrupting synteny near “sensitive sites” (Corbett‐Detig, ). Although we recognize there a number of direct physical effects of inversion mutations that selection can potentially act on, here we conclude that breakpoint lesions have had minimal effects in generating phenotypic variation through the structural or expression alterations of boundary genes.…”

Genomics of Natural Populations: Evolutionary Forces that Establish and Maintain Gene Arrangements inDrosophila pseudoosbscura

“…Sensitive sites normally promote crossing over, however, an inversion can lead reduce levels of genetic exchange when near the sensitive sites. Corbett-Detig (2016) concluded this can lead to a selective advantage for the inversion. Here, we conclude that breakpoint lesions have had minimal effects in generating phenotypic variation through the structural or expression alterations of boundary genes for selection to act on, however, further studies that map D. pseudoobscura TADs in different arrangements, test for meiotic drive in heterozygotes, and map sensitive sites in D. pseudoobscura are needed to fully reject the position effect hypothesis.…”

“…Certain cross over events could lead to chromatids that differ in length such that shorter chromatids are transmitted at higher frequencies. Finally, Corbett-Detig (2016) showed that large inversions are often in close proximity to “sensitive sites” in the D. melanogaster genome. Sensitive sites normally promote crossing over, however, an inversion can lead reduce levels of genetic exchange when near the sensitive sites.…”

Meiotic Drive and Survival Probability of Newly Inverted Chromosomes

“…In this case pericentric inversions that did not exhibit expected underdominance were those whose breakpoints disrupted "sensitive sites" necessary for normal crossing over (Coyne et al 1993). Interestingly, Corbett-Detig (2016) showed that breakpoints of cosmopolitan and recurrent paracentric inversions in D. melanogaster are closer to cytological bands containing sensitive sites than the breakpoints of rare inversions. This pattern was interpreted as evidence of positive selection for recombination suppression per se, but upon considering the crossover dependent fertility underdominance generated by overlapping paracentric inversions it would appear common cosmopolitan inversions' proximity to sensitive sites prevents them from suffering the effects of underdominance when heterozygous with another inversion.…”

“…The distribution of inversion breakpoints along a chromosome has been particularly informative, as these breakpoints exhibit several nonrandom patterns that have inspired models of inversion evolution (Federer et al 1967, Van Valen and Levins 1968, Krimbas and Powell 1992. One class of models explains the distribution of inversion breakpoints in terms of selection for inversion length or chromosomal placement and the resulting recombination suppression (Caceres et al 1997, Cáceres et al 1999, Corbett-Detig 2016. Alternately, inversion breakpoint patterns have been attributed to non-selective mechanisms by: 1) modeling the spontaneous mutational process as transposable element mediated, 2) using directionally biased spontaneous mutation rates, or 3) considering structural heterozygosity as autocatalytic, such that pairing difficulty at breakpoints causes chromosomal breakage and elevates rates of gene rearrangement (Novitski 1946, Bernstein and Goldschmidt 1961, Lim and Simmons 1994.…”