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This paper reports the results of the first statewide survey of the freshwater mussels of Nebraska. Survey goals were: (1) to document current distributions through collection of recent shells; (2) to document former distributions through collection of relict shells and examination of museum collections; (3) to identify changes in distribution; (4) to identify the primary natural and anthropomorphic factors impacting unionids; and (5) to develop a model to explain the documented distributions. The survey confirmed 30 unionid species and the exotic Corbicula fluminea for the state, and museum vouchers documented one additional unionid species. Analysis of museum records and an extensive literature search coupled with research in adjacent states identified 13 additional unionid species with known distributions near the Nebraska border. Some of these unionids may have formerly inhabited the state. Seven documented species have probably been extirpated, and the ranges of 15 others have contracted significantly. Only nine species are relatively stable at present, and one of these is extremely rare and federally endangered. Diversity is concentrated in the formerly glaciated portion of eastern Nebraska, and drops abruptly along the Missouri River to the east and in the Great Plains westward. The primary natural factors influencing unionid distributions in Nebraska include availability of perennially flowing waters, host fish diversity, substrate composition and stability, and formerly heavy sediment loads. Anthropomorphic factors are surface and subsurface irrigation withdrawals, construction of canals and reservoirs, channelization, erosion, intensive grazing, contaminants, and the introduction of invasive species. Unionid presence and diversity largely correlates with substrate stability. Stream orientation and morphology in portions of eastern Nebraska promote slow currents, and substrates composed of mud, sand, and rock provide greater stability than the shifting sand substrates common elsewhere in the state. In central and western Nebraska, unionid populations are concentrated in headwaters, backwaters, and side-channels of rivers, and canals, reservoirs, and small tributaries, while the generally shifting sand habitats of most rivers provide relatively little viable habitat. In the historic Missouri River, unstable substrates and (formerly) heavy sediment loads limited diversity to silt tolerant species, and viable habitat largely to backwaters, sloughs, attached lakes, side channels, and relatively few main channel environments. Today, upstream dams have greatly reduced the sediment load in the Missouri River, but unstable substrates restrict mussels to backwaters, side channels, pools below wing dams, revetments, and other areas sheltered from strong currents. Channelization and erosion/sedimentation have destroyed or drastically impacted stream habitats in eastern Nebraska resulting in the loss of much of the original unionid diversity. Surface and subsurface irrigation coupled with related declines in water tables have eliminated habitat in western Nebraska, though losses are partially compensated for some species by colonization of viable reaches of newly created impoundments and canals. Intensive grazing along streams and agricultural pollution further exacerbate habitat degradation and pressure remaining unionid populations. Invasive species directly compete with native mussels for sustenance and living space and may become serious threats to the survival of remaining unionid species in some habitats.