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[Preprint]. 2025 May 16:2025.05.13.651073.
doi: 10.1101/2025.05.13.651073.

Loss of the cytosolic DNA-sensing genes CGAS and STING1 in armadillos (Cingulata)

Lillie Schaffer  1 , Amanda Ivanoff  1 , Frédéric Delsuc  2 , Vincent J Lynch  1
Affiliations

Loss of the cytosolic DNA-sensing genes CGAS and STING1 in armadillos (Cingulata)

Lillie Schaffer et al. bioRxiv. .

Abstract

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 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.

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Figures

Figure 1:
Figure 1:
Evolutionary loss of CGAS-STING1 in armadillos. Genomic organization of CGAS and STING1 exons represented in the phylogenetic context of the 15 investigated xenarthran species (five sloths, three anteaters, and seven armadillos). Functional genes found in sloths and anteaters are represented in blue, and armadillo pseudogenes in white. Dashed line contours show exons missing in current genomic assemblies. Frameshifts (!), stop-codons (*), and splice site mutations (red stars) are indicated in armadillo pseudogenes. Sequence alignments present examples of inactivating mutations in exons shared by all armadillos, indicating that both CGAS and STING1 were lost in their common ancestor 45 to 70 million years ago (Mya). Xenarthran phylogeny and timescale according to Gibb et al. (2016). Paintings by Carl Buell (copyright John Gatesy) and Michelle S. Fabros.
See this image and copyright information in PMC

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