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Elevation has a strong effect on aquatic microbiome. However, we know little about the effects of elevation on functional genes, especially antibiotic resistance genes (ARGs) and organic remediation genes (ORGs) in freshwater ecosystems. In this study, we analyzed five classes of functional genes including ARGs, metal resistance genes (MRGs), ORGs, bacteriophages, and virulence genes between two high-altitude lakes (HALs) and two low-altitude lakes (LALs) in Mountain Siguniang at Eastern Tibetan Plateau by means of GeoChip 5.0. No differences (Student's t-test, p > 0.05) of gene richness including ARGs, MRGs, ORGs, bacteriophages, and virulence genes in HALs and LALs were found. The abundance of most ARGs and ORGs was higher in HALs than in LALs. For MRGs, the abundance of macro metal resistance genes of potassium, calcium, and aluminum was higher in HALs than in LALs (Student's t-test, p < 0.05; all Cohen's d > 0.8). The abundance of some heavy metal resistance genes of lead and mercury was lower in HALs than in LALs (Student's t-test, p < 0.05; all Cohen's d < -0.8). The composition of these functional genes in HALs differed significantly from in LALs. The functional gene network in HALs was also more complex than that in LALs. We speculate that enrichment of ARGs and ORGs in HALs is related to different microbial communities, exogenous ARGs, and enriched persistent organic pollutants through long-range atmospheric transport driven by the Indian monsoon. This study highlights the unexpected enrichment of ARGs, MRGs, and ORGs in remote lakes at high elevations., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)