Contemporary species distributions and geographic patterns of genetic structure largely reflect pre-historic events, often with subsequent alterations from human influences. The geographic genetic structure of a relatively common and widespread unionid species, Quadrula quadrula, was investigated to reconstruct its postglacial history. Hypotheses regarding colonization routes of Q. quadrula into the Great Lakes basin after the most recent glacial retreat were tested. Samples were collected from Q. quadrula at sites spanning hypothesized glacial refugia and postglacial expansion routes in the Mississippi River drainage, including the Ohio and Missouri rivers, and the Great Lakes. Broad-scale phylogeography and population structure were assessed by sequencing a fragment of the mitochondrial CO1 gene and genotyping eight microsatellites. Results of analyses showed marked differences among the Great Lakes, Mississippi River, and Ohio River drainages, and suggested colonization of the Great Lakes basin from a Mississippian source. Populations showed patterns of isolation by distance: geographic and genetic distances were significantly correlated among Great Lakes populations based on colonization through the Chicago–Illinois outlet, but not when following the Wabash–Maumee outlet. All evidence indicates that postglacial colonization of the Great Lakes basin occurred almost exclusively through the Chicago–Illinois outlet, with subsequent expansion into the lower Great Lakes.
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