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Approximately two-dozen species in three genera of the Neotropical suckermouth armored catfish family Loricariidae are the only described fishes known to specialize on diets consisting largely of wood. We conducted a molecular phylogenetic analysis of 10 described species and 14 undescribed species or morphotypes assigned to the wood-eating catfish genus Panaqolus , and four described species and three undescribed species or morphotypes assigned to the distantly related wood-eating catfish genus Panaque . Our analyses included individuals and species from both genera that are broadly distributed throughout tropical South America east of the Andes Mountains and 13 additional genera hypothesized to have also descended from the most recent common ancestor of Panaqolus and Panaque . Bayesian and maximum likelihood analyses of two mitochondrial and three nuclear loci totaling 4293 bp confirmed respective monophyly of Panaqolus , exclusive of the putative congener ‘ Panaqolus ’ koko , and Panaque . Members of Panaqolus sensu stricto were distributed across three strongly monophyletic clades: a clade of 10 generally darkly colored, lyretail species distributed across western headwaters of the Amazon Basin, a clade of three irregularly and narrowly banded species from the western Orinoco Basin, and a clade of 11 generally brown, broadly banded species that are widely distributed throughout the Amazon Basin. We erect new subgenera for each of these clades and a new genus for the morphologically, biogeographically and ecologically distinct species ‘ Panaqolus ’ koko . Our finding that perhaps half of the species-level diversity in the widespread genus Panaqolus remains undescribed illustrates the extent to which total taxonomic diversity of small and philopatric, yet apparently widely distributed, Amazonian fishes may remain underestimated. Ranges for two Panaqolus subgenera and the genus Panaque overlap with the wood-eating genus Cochliodon in central Andean tributaries of the upper Amazon Basin, which appear to be a global epicenter of wood-eating catfish diversity. [ABSTRACT FROM AUTHOR]