Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

Bats are the only mammals capable of sustained flight and are increasingly recognized as one of the most important natural reservoir for some of the world's most lethal viruses, including Nipah, Hendra, Ebola, Marburg and SARS-CoV. This, combined with their exceptional longevity and low tumorigenesis 11 , has raised an intriguing question on whether these seemingly unrelated biological features are actually intertwined and that they all represent different outcomes of the long evolutionary adaption to flight -an absolute unique biological ability only acquired by bats among all mammals. Comparative genomic studies have revealed an unexpected concentration of positively selected genes in the DNA damage checkpoints and immunity pathways that may be related to the origin of flight 56 . More recently, we have reported findings from a wider comparative genomic study, indicating bats are the only mammals which have lost the entire PYHIN gene family, which encodes DNA sensors highly important for dsDNA-triggered inflammation 57 . Taken together, these preliminary discoveries point to the possibility that bats have evolved an immune system, or an innate defense system that is more robust and tolerant to stress signals or stimuli (such as infection and DNA damage) as compared to other mammals, which in turn enables them to live longer and be more resilient to various pathogens.