Schaffer, L.; Ivanhoff, A. N.; Delsuc, F.; Lynch, V. J.

The principal sensor of intracellular double-stranded DNA (dsDNA) is cyclic GMP-AMP synthase (cGAS), which generates the second messenger cyclic GMP-AMP that binds stimulator of interferon genes (STING), leading to the expression of type I interferon genes. cGAS and STING1 also play essential roles in maintaining genome integrity and the initiation and progression of cancer. Here we show that cGAS and STING1 were pseudogenized in the ancestral armadillo branch 45 to 70 million years ago. The complete loss of the cGAS-STING1 pathway in armadillos suggests this lineage has evolved alternate ways to sense intracellular double-stranded DNA, which may be related to their extreme cancer resistance.