Collaborative Research: Reversing evolution to understand the genetic basis of species divergence

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One of the most fundamental quests of Evolutionary Biology is to understand how biodiversity arises through adaptation and speciation. Genes involved in adaptation or isolation between species are frequently located in regions of a chromosome where the ancestral gene order has flipped. These inverted chromosome regions block gene exchange between closely related species, which allows the genes inside them to evolve independently. It is not known whether those key genes are randomly spread inside the inversions or whether they are more likely found close to the edges or the center of those inverted regions. Circumventing the barriers to genetic analyses posed by inversions will allow researchers to learn the genetic basis of species divergence and adaptation. This project will use the Drosophila (fruit fly) genome editing toolkit to reverse the outcome of the evolutionary process and flip back the large chromosomal inversions that separate Drosophila pseudoobscura and D. persimilis. This will allow unprecedented analyses of important species divergence traits linked to these inversions. This research will also have educational impacts in K-12 education and teacher training via collaboration with public school teachers from local minority high schools. Moreover, chromosome inversions cause many important human diseases. Understanding where the critical sequences lie is fundamental to development of treatment of those diseases. An important mechanism that allows species to persist in the face of gene flow is the presence of chromosomal inversions. Although considered impermeable barriers to gene flux in heterozygotes, chromosomal inversions can exchange genetic material via double-crossovers or non-crossover gene conversion. Those processes should be more common in the central regions of inversions. Theoretical studies thus predict that nucleotide divergence between species differing by inversions should be higher at the breakpoint regions relative to the center, and that adaptive or reproductive isolation genes should also be more likely located towards the breakpoints. Tests of the first prediction have been conducted using population genetic or comparative genomic data, resulting in a range of inconsistent patterns suggesting that theoretical models may oversimplify the expected effects of inversions on recombination. Test of the second prediction, on the other hand, have been impossible to conduct because inversions reduce or impede recombination in hybrids, precluding fine scale genetic analysis of interspecific differences at those genomic regions. To overcome this limitation, this project will leverage CRISPR/Cas9 genome editing technology to revert two fixed inversions between the sibling fruit fly species Drosophila pseudoobscura and D. persimilis. The strains that will be generated will be used for genetic mapping of reproductive isolation factors (hybrid male sterility), and for an experimental evolution study that will test whether and how much chromosomal inversions facilitate the persistence of hybridizing species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.