Most adaptation is thought to occur through the fixation of numerous alleles at many different loci. Consequently, the independent evolution of similar phenotypes is predicted to occur through different genetic mechanisms. The genetic basis of adaptation is still largely unknown, however, and it is unclear whether adaptation to new environments utilizes ubiquitous small-effect polygenic variation or large-effect alleles at a small number of loci. To address this question, we examined the genetic basis of bony armor loss in three freshwater populations of Alaskan threespine stickleback, Gasterosteus aculeatus, that evolved from fully armored anadromous populations in the last 14,000 years. Crosses between complete-armor and low-armor populations revealed that a single Mendelian factor governed the formation of all but the most anterior lateral plates, and another independently segregating factor largely determined pelvic armor. Genetic mapping localized the Mendelian genes to different chromosomal regions, and crosses among these same three widely separated populations showed that both bony plates and pelvic armor failed to fully complement, implicating the same Mendelian armor reduction genes. Thus, rapid and repeated armor loss in Alaskan stickleback populations appears to be occurring through the fixation of largeeffect variants in the same genes.A central tenet of evolutionary theory is that adaptation in the wild, like artificial selection, occurs gradually through the sequential fixation of small-effect variants (1). Consequently, the independent evolution of similar phenotypes is expected to use unique combinations of genes and alleles (2). New populations, however, are often established in novel environments at the edge of an organism's range, and selective pressures faced in these new habitats are often an important causative factor for adaptive radiations (3). Importantly, novel environments may also have immediate disruptive effects on developmental processes that can expose novel genetic variants, some of which may have large effects on evolving phenotypes (4, 5). The importance of genes of major effect is currently the focus of renewed research (6, 7). The role of major effect genes during adaptation, however, is still unclear, as is the frequency with which recurrent phenotypic evolution occurs through changes in the same (8-11) or different (8,12,13) genes. In addition, the genetics of adaptation has most often been studied in the laboratory (14), with much less work in natural populations (13). To address these problems, we have taken advantage of a unique natural system, the rapid postglacial diversification of threespine stickleback, Gasterosteus aculeatus (15). Thousands of coastal freshwater populations of stickleback have derived independently from anadromous (sea-run) ancestors. Phenotypically similar throughout their range, anadromous stickleback are protected with bony armor including lateral plates and a robust set of dorsal and pelvic spines (Fig. 1D). In contrast, derived lacustrine pop...