ABCB1 AS A NOVEL INSIGHT FOR THE UNIQUENESS OF BATS

Abstract

Bats are the only mammals to have attained true flight. In addition, they possess the unique characteristics of longevity, being reservoir for numerous deadly viruses and low tumorigenesis rate. For decades, bat biologists have hypothesized theories to how bats have acquired such characteristics. However, these theories lacked mechanistic evidences to support their claim. Our recent comparative genome analysis of two different bat species, Pteropus alecto and Myotis davidii, suggested that bats have an improved DNA damage resistance, possibly via an evolutionary positively selected DNA damage response pathway. Unexpectedly, treatment of γ-irradiation to human, mouse and bat cells demonstrated no significant differences in their γH2AX response. Instead, bat cells exhibited exceptional resilience to DNA damage induced by genotoxic agents in comparison to the other mammals. Using doxorubicin, we found that the mechanism of DNA damage resistance was due to bat cells intrinsically possess the ability of drug efflux via ABC transporters. Additionally, we identified ABCB1 as the sole ABC transporter responsible. Together, our findings indicate that bats possess a broad and unique ABCB1 expression to protect from DNA damage.