TY - JOUR T1 - Allelic polymorphism at foxo contributes to local adaptation in Drosophila melanogaster JF - bioRxiv DO - 10.1101/471565 SP - 471565 AU - Nicolas J. Betancourt AU - Subhash Rajpurohit AU - Esra Durmaz AU - Daniel K. Fabian AU - Martin Kapun AU - Thomas Flatt AU - Paul Schmidt Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/11/16/471565.abstract N2 - The insulin insulin-like growth factor signaling pathway has been hypothesized as a major determinant of life history profiles that vary adaptively in natural populations. In Drosophila melanogaster, multiple components of this pathway vary predictably with latitude; this includes foxo, a conserved gene that regulates insulin signaling and has pleiotropic effects on a variety of fitness-associated traits. We hypothesized that allelic variation at foxo underlies genetic variance for traits that vary with latitude and reflect local adaptation. To evaluate this, we generated recombinant outbred populations in which the focal foxo allele was homozygous and fixed for either the allele common at high latitude or low latitude and the genomic background was randomized across 20 inbred lines. After eight generations of recombination, experimental populations were phenotyped for a series of traits related to gene function. Our results demonstrate that natural allelic variation at foxo has major and predictable effects on body size and starvation tolerance, but not on development time. These patterns mirror those observed in natural populations collected across the latitudinal gradient in the eastern U.S.: clines were observed for starvation tolerance and body size, but development time exhibited no association with latitude. Furthermore, differences in size between foxo genotypes were equivalent to those observed between populations sampled from the latitudinal extremes, although contribution to the genetic variance for starvation tolerance was less pronounced. These results suggest that allelic variation at foxo is a major contributor to adaptive patterns of life history variation in natural populations of this genetic model. ER -