Principles of Genome Evolution in the Drosophila melanogaster Species Group

Abstract

That closely related species often differ by chromosomal inversions was discovered by Sturtevant and Plunkett in 1926. Our knowledge of how these inversions originate is still very limited, although a prevailing view is that they are facilitated by ectopic recombination events between inverted repetitive sequences. The availability of genome sequences of related species now allows us to study in detail the mechanisms that generate interspecific inversions. We have analyzed the breakpoint regions of the 29 inversions that differentiate the chromosomes of Drosophila melanogaster and two closely related species, D. simulans and D. yakuba, and reconstructed the molecular events that underlie their origin. Experimental and computational analysis revealed that the breakpoint regions of 59% of the inversions (17/29) are associated with inverted duplications of genes or other nonrepetitive sequences. In only two cases do we find evidence for inverted repetitive sequences in inversion breakpoints. We propose that the presence of inverted duplications associated with inversion breakpoint regions is the result of staggered breaks, either isochromatid or chromatid, and that this, rather than ectopic exchange between inverted repetitive sequences, is the prevalent mechanism for the generation of inversions in the melanogaster species group. Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance. The organization of genes on chromosomes changes over evolutionary time. In some organisms, such as fruit flies and mosquitoes, inversions of chromosome regions are widespread. This has been associated with adaptation to environmental pressures and speciation. However, the mechanisms by which inversions are generated at the molecular level are poorly understood. The prevailing view involves the interactions of sequences that are moderately repeated in the genome. Here, we use molecular and computational methods to study 29 inversions that differentiate the chromosomes of three closely related fruit fly species. We find little support for a causal role of repetitive sequences in the origin of inversions and, instead, detect the presence of inverted duplications of ancestrally unique sequences (generally protein-coding genes) in the breakpoint regions of many inversions. This leads us to propose an alternative model in which the generation of inversions is coupled with the generation of duplications of flanking sequences. Additionally, we find evidence for genomic regions that are prone to breakage, being associated with inversions generated independently during the evolution of the ancestors of existing species.