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Hybridization and introgression permitted gene transfer from Catostomus to Lake Suckers in modern and MioPliocene lakes of Western United States. Lake Sucker genera, Chasmistes, Deltistes, and Xyrauchen, were sympatric with species of Catostomus (riverine suckers) in four large modern lakes and many fossil lakes in the Great Basin, Klamath, and Columbia-Snake drainages, and also in the Colorado River. Unique morphological traits in Lake Suckers originally included distinctive lips, jaw bones, neurocranial bones, and gill-rakers, but many of the original traits were lost or partly lost, and the remaining phenotypes are mixtures of intermediate morphological traits grading toward local species of Catostomus. The intermediates are comparable to patterns in other vertebrate interspecifc hybrids. The fossil record documents Catostomus and Lake Suckers in many lacustrine localities between the Sierra Nevada and the Great Basin at least 7 million years ago; but mitochondrial DNA of each species of Lake Sucker is now more like its sympatric or nearby Catostomus than to other Lake Suckers, indicating mtDNA transfer after or during several million years of evolution. Morphological cladistic, DNA, chromosome, and fossil analyses of Lake Suckers suggest that the mixed-phenotye pattern in Lake Suckers is consistent with hypothesized introgression rather than recent origin of Chasmistes phenotypes from sympatric Catostomus. Catostomids are tetraploid with duplicate genes at many loci. Duplicate chromosomes and genes may shield these organisms from the effects of hybrid mismatched genomes, but not without dosage distortion and related conflicts, including possible sterility.