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Aim: Natural range expansions and human‐mediated colonizations usually involve a small number of individuals that establish new populations in novel habitats. In both cases, founders carry only a fraction of the total genetic variation of the source populations. Here, we used native and non‐native populations of the green anole, Anolis carolinensis, to compare the current distribution of genetic variation in populations shaped by natural range expansion and human‐mediated colonization.

Location: North America, Hawaiian Islands, Western Pacific Islands.

Methods: We analysed 401 mtDNA haplotypes to infer the colonization history of A. carolinensis on nine islands in the Pacific Ocean. We then genotyped 576 individuals at seven microsatellite loci to assess the levels of genetic diversity and population genetic differentiation for both the native and non‐native ranges.

Results: Our findings support two separate introductions to the Hawaiian Islands and several western Pacific islands, with subsequent colonizations within each region following a stepping‐stone model. Genetic diversity at neutral markers was significantly lower in the non‐native range because of founder effects, which also contributed to the increased population genetic differentiation among the non‐native regions. In contrast, a steady reduction in genetic diversity with increasing distance from the ancestral population was observed in the native range following range expansion.

Main conclusions: Range expansions cause serial founder events that are the spatial analogue of genetic drift, producing a pattern of isolation‐by‐distance in the native range of the species. In human‐mediated colonizations, after an initial loss of genetic diversity, founder effects appear to persist, resulting in overall high genetic differentiation among non‐native regions but an absence of isolation‐by‐distance. Contrasting the processes influencing the amount and structuring of genetic variability during natural range expansion and human‐mediated biological invasions can shed new light on the fate of natural populations exposed to novel and changing environments.