Schaffer Lillie, Ivanoff Amanda, Delsuc Frédéric, Lynch Vincent J
Department of Biological Sciences, University at Buffalo, SUNY, 551 Cooke Hall, Buffalo, NY, 14260, USA.
Institut des Sciences de l'Evolution de Montpellier (ISEM), CNRS, IRD, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier, France.
bioRxiv. 2025 May 16:2025.05.13.651073. doi: 10.1101/2025.05.13.651073.
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 (STING1), 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 and were pseudogenized in the ancestral armadillo branch 45 to 70 million years ago. The complete loss of the - 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.
细胞内双链DNA（dsDNA）的主要传感器是环磷酸鸟苷-腺苷酸合成酶（CGAS），它产生第二信使环磷酸鸟苷-腺苷酸，后者与干扰素基因刺激因子（STING1）结合，导致I型干扰素基因的表达。CGAS和STING1在维持基因组完整性以及癌症的起始和发展过程中也发挥着重要作用。在这里，我们表明[具体基因]在4500万至7000万年前的犰狳祖先分支中被假基因化。犰狳中[该基因]通路的完全丧失表明，这一谱系已经进化出了感知细胞内双链DNA的替代方式，这可能与它们对癌症的极端抗性有关。
