Urbanization significantly alters natural ecosystems and has accelerated globally. Urban wildlife populations are often highly fragmented by human infrastructure, and isolated populations may adapt in response to local urban pressures. However, relatively few studies have identified genomic signatures of adaptation in urban animals. We used a landscape genomics approach to examine signatures of selection in urban populations of white-footed mice (Peromyscus leucopus) in New York City. We analyzed 154,770 SNPs identified from transcriptome data from 48 P. leucopus individuals from three urban and three rural populations, and used outlier tests to identify evidence of urban adaptation. We accounted for demography by simulating a neutral SNP dataset under an inferred demographic history as a null model for outlier analysis. We also tested whether candidate genes were associated with environmental variables related to urbanization. In total, we detected 381 outlier loci and after stringent filtering, identified and annotated 19 candidate loci. Many of the candidate genes were involved in metabolic processes, and have well-established roles in metabolizing lipids and carbohydrates. Our results indicate that white-footed mice in NYC are adapting at the biomolecular level to local selective pressures in urban habitats. Annotation of outlier loci suggest selection is acting on metabolic pathways in urban populations, likely related to novel diets in cities that differ from diets in less disturbed areas.
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