Assessing evidence for adaptive evolution in two hearing-related genes important for high-frequency hearing in echolocating mammals.

High-frequency hearing is particularly important for echolocating bats and toothed whales. Previously, studies of the hearing-related genes Prestin, KCNQ4, and TMC1 documented that adaptive evolution of high-frequency hearing has taken place in echolocating bats and toothed whales. In this study, we present two additional candidate hearing-related genes, Shh and SK2, that may also have contributed to the evolution of echolocation in mammals. Shh is a member of the vertebrate Hedgehog gene family and is required in the specification of the mammalian cochlea. SK2 is expressed in both inner and outer hair cells, and it plays an important role in the auditory system. The coding region sequences of Shh and SK2 were obtained from a wide range of mammals with and without echolocating ability. The topologies of phylogenetic trees constructed using Shh and SK2 were different; however, multiple molecular evolutionary analyses showed that those two genes experienced different selective pressures in echolocating bats and toothed whales compared to nonecholocating mammals. In addition, several nominally significant positively selected sites were detected in the nonfunctional domain of the SK2 gene, indicating that different selective pressures were acting on different parts of the SK2 gene. This study has expanded our knowledge of the adaptive evolution of high-frequency hearing in echolocating mammals.