Gene expression and adaptive evolution of ZBED1 in the hibernating greater horseshoe bat (Rhinolophus ferrumequinum)

Mammalian hibernators experience physiological extremes, e.g. ischemia, muscle disuse and hypothermia, which are lethal to non-hibernators, implying the existence of underlying mechanisms that allow hibernators to withstand these physiological extremes. Increased cell proliferation is suggested to be such a strategy, but its molecular basis remains unknown. In this study, we characterized the expression pattern of ZBED1 (zinc finger, BED-type containing 1), a transcription factor that plays a crucial role in regulating cell proliferation, in five tissues of the greater horseshoe bat (Rhinolophus ferrumequinum) during pre-hibernation, deep hibernation and post-hibernation. Moreover, we investigated the ZBED1 genetic divergence from individuals with variable hibernation phenotypes that cover all three known mtDNA lineages of the species. Expression analyses showed that ZBED1 is overexpressed only in brain and skeletal muscle, not in the other three tissues, suggesting an increased cell proliferation in these two tissues during deep hibernation. Evolutionary analyses showed that ZBED1 sequences were clustered into two well-supported clades with each one dominated by hibernating and non-hibernating individuals, respectively. Positive selection analyses further showed some positively selected sites and a divergent selection pressure among hibernating and non-hibernating groups of R.ferrumequinum. Our results suggest that ZBED1 as a potential candidate gene that regulates cell proliferation for hibernators to face physiological extremes during hibernation.