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Abstract When species are continuously distributed across environmental gradients, the relative strength of selection and gene flow shape spatial patterns of genetic variation, potentially leading to variable levels of differentiation across loci. Determining whether adaptive genetic variation tends to be structured differently than neutral variation along environmental gradients is an open and important question in evolutionary genetics. We performed exome-wide population genomic analysis on deer mice sampled along an elevational gradient of nearly 4000 m of vertical relief. Using a combination of selection scans, genotype-environment associations, and geographic cline analyses, we found that a large proportion of the exome has experienced a history of altitude-related selection. Elevational clines for nearly 30% of these putatively adaptive loci were shifted significantly up- or down-slope of clines for loci that did not bear similar signatures of selection. Many of these selection targets can be plausibly linked to known phenotypic differences between highland and lowland deer mice, although the vast majority of these candidates have not been reported in other studies of highland taxa. Together, these results suggest new hypotheses about the genetic basis of physiological adaptation to high-altitude, and the spatial distribution of adaptive genetic variation along environmental gradients.